Percutaneous Absorption of Nicardipine and Ketorolac in Rhesus Monkeys

Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.     

LTA and FAU-X Iron-Enriched Zeolites: Use for Phosphate Removal from Aqueous Medium

Hydrothermally synthesized Linde type A (LTA) and faujasite X (FAU-X) zeolites are low-cost and environmentally benign inorganic carriers for environmental applications. In this study, (oxy)hydroxides were incorporated onto LTA and FAU-X zeolites to promote the phosphate adsorption. The performance of LTA-Fe and FAU-X-Fe was evaluated through batch adsorption assays. A complete evaluation was performed to recover phosphate from synthetic wastewater. The effect of pH, concentration, equilibrium, and kinetic parameters on phosphate adsorption and its further reuse in sorption–desorption cycles were evaluated. LTA-Fe and FAU-X-Fe are effective for adsorption of phosphate at neutral (e.g., pH 7.0 ± 0.2) and in a broad range of phosphate concentrations. Higher ratios of adsorption capacities were obtained by synthetic zeolites enriched with iron in comparison to their parent forms. The phosphate adsorption occurred through hydrogen bonding and complexation reactions between protonated iron hydroxyl groups and phosphate anions. The phosphate monolayer adsorption was followed by diffusion through the internal pores and 80% of the equilibrium adsorption was reached within 50 min. The LTA-Fe and FAU-X-Fe can be used for phosphate recovery from wastewater treatment plants. The use of LTA-Fe and FAU-X-Fe in a tertiary wastewater treatment stage could allow to reduce the phosphate–phosphorous content, reaching the regulatory levels (equal 1 mg L⁻¹ total phosphorous). The phosphate adsorption using LTA-Fe and FAU-X-Fe does not require pH adjustment, and it is endothermic. The reusability of both iron zeolites is limited, and they can be finally disposed for soil amendment applications.     

Objective assessment of the human visual attentional state

Primary objective

The purpose of this study was to develop an objective way to assess human visual attention using the alpha-band component of the visual-evoked potential (VEP).

Design and methods

Six different attentional conditions were tested: eyes-open, eyes-closed, eyes-closed with backwards number counting, and three rapid-serial visual presentation (RSVP) tasks. Eighteen visually normal, young-adult subjects (ages 21–28 years) were tested binocularly at 1 m for each condition on two separate days. The Diopsys? NOVA-TR system was used to obtain the visual-evoked potential (VEP) and extracted alpha wave and its related power spectrum. Additionally, the Visual Search and Attention Test (VSAT) was administered as a subjective measure of visual attention.

Results

Subjects exhibited significant decreases in power in the alpha band when comparing the eyes-closed with the eyes-open conditions, with power in the eyes-closed condition being, on average, twice as large. The response from the other four conditions did not reflect the differential attentional demands. The ratio of the power in the eyes-closed condition to the eyes-open condition in the lower-alpha frequencies (8–10 Hz) was found to be significantly correlated with the group’s performance on the VSAT, especially the 10-Hz component.

Conclusions

An individual’s ability to attenuate their alpha component during visual processing may be a predictor of their visual attentional state. These findings solidify the role of the VEP alpha subcomponent as an objective electrophysiological correlate of visual attention, which may be useful in the diagnosis and treatment of human visual attention disorders in the future.     

Deferoxamine-induced growth retardation in patients with thalassemia major

In the retrospective study reported here, we compared the longitudinal growth in three groups of children with thalassemia major who received a similar transfusion program but different schedules of chelation treatment. In those patients who initiated deferoxamine (DF) administration by daily subcutaneous infusion (50 to 80 mg/kg/day) simultaneously with the beginning of transfusion (at 8 +/- 6 months), mean height at 2 to 6 years of age was significantly reduced in comparison (1) with those patients who initiated DF subcutaneous treatment after 3 years at similar doses and (2) with those who were treated intramuscularly with small doses. In the patients treated at an early stage, those with more marked stunted growth had a clinical and radiologic ricketslike syndrome associated with joint stiffness. Mineral metabolism studies in these patients showed a reduction of hair and leukocyte zinc levels and leukocyte alkaline phosphatase activity. Our findings indicate that DF administration at high doses by continuous infusion before iron overload has been established adversely affects longitudinal growth. By contrast, after 3 years of age, even large doses (in the order of 100/mg/kg/day) did not result in growth retardation. The growth retardation observed may be related to chelation of other trace elements, including zinc, in the presence of low iron burden, to the direct toxic effect of unchelated DF by interference with critical iron-dependent enzymes, or both. These results indicate that in patients with thalassemia major, DF administration should be initiated only after iron accumulation is established, namely, around 3 years of age, after 20 to 30 transfusions, which are usually associated with ferritin levels in the range of 800 to 1000 ng/ml. At this age, deferoxamine doses should be established on the basis of iron balance studies and dose response curves. Doses higher than 50 to 60 mg/kg do not adversely affect growth but produce toxic side effects on acoustic and visual pathways and therefore should not be used. Longitudinal growth monitoring of DF-treated patients is warranted.     

Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.     

Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?

BACKGROUND:

To quantify the magnitude of benefit of the addition of hormone treatment (HT) to exclusive radiotherapy for locally advanced prostate cancer, a literature‐based meta‐analysis was conducted.

METHODS:

Event‐based relative risks (RR) with 95% confidence intervals (CIs) were derived through a random‐effect model. Differences in primary (biochemical failure and clinical progression‐free survival) and secondary outcomes (cancer‐specific survival, overall survival [OS], recurrence patterns, and toxicity) were explored. Absolute differences and numbers of patients needed to treat (NNT) were calculated. A heterogeneity test, a metaregression analysis with clinical predictors of outcome, and a correlation analysis for surrogate endpoints were also performed.

RESULTS:

Seven trials (4387 patients) were gathered. Hormone suppression significantly decreased both biochemical failure (RR, 0.76; 95% CI, 0.70‐0.82; P < .0001) and clinical progression‐free survival (RR, 0.81; 95% CI 0.71‐0.93; P = .002), with absolute differences of 10% and 7.7%, respectively, which translates into 10 and 13 NNT. cancer‐specific survival (RR, 0.76; 95% CI, 0.69‐0.83; P < .0001) and OS (RR, 0.86; 95% CI, 0.80‐0.93; P < .0001) were also significantly improved by the addition of HT, without significant heterogeneity, with absolute differences of 5.5% and 4.9%, respectively, which translates into 18 and 20 NNT. Local and distant relapse were significantly decreased by HT, by 36% and 28%, respectively, and no significant differences in toxicity were found. Primary and secondary efficacy outcomes were significantly correlated.

CONCLUSIONS:

Hormone suppression plus radiotherapy significantly decreases recurrence and mortality of patients with localized prostate cancer, without affecting toxicity. Cancer 2009. © 2009 American Cancer Society.