The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role strain in couples with and without a child with a chronic illness: associations with marital satisfaction, intimacy, and daily mood

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.     

A Dilution Stack Sampler for Collection of Organic Aerosol Emissions: Design,Characterization and Field Tests

A dilution stack sampler specifically intended to collect fine organic aerosol from combustion sources while minimizing sample contamination has been designed and tested. The sampler simulates the cooling and dilution processes that occur in the plume downwind of a combustion source, so that the organic compounds which condense under ambient conditions will be collected as particulate matter. The special features of this sampler are described in detail, and compared with other stack sampling systems. The results of both laboratory and field tests of the system are discussed. Collection of organic aerosol using this sampler is compared with collection using EPA Method 5.     

Advances in Modeling Completely Mixed Flow Reactors for Ion Exchange

This work advances the mathematical modeling of ion exchange treatment in completely mixed flow reactors in which there is recycle and regeneration of the ion exchange resin. The most common application of this process is magnetic ion exchange resin to remove dissolved organic carbon from raw drinking water. The motivation for this work was the complex distribution of resin particle ages and sizes that result from the recycle and regeneration processes. The newly developed model uses a single “age-averaged” diffusion equation to represent resin particle age as compared with the previous Monte Carlo model that uses a large number of diffusion equations to represent various resin particle ages. Advantages of the age-averaged model over the Monte Carlo model include a closed-form analytical solution for the steady-state case of the model, advanced numerical techniques used for the nonsteady-state case of the model, and model simulations require much less computational time and yield more accurate results. The age-averaged model is a robust numerical tool that can be used to evaluate a range of treatment scenarios as a result of these advancements.     

Leachability of degradation products from hard chairside reline resins in artificial saliva: Effect of water‐bath post‐polymerization treatment

The effect of a post‐polymerization treatment on the leaching of methacrylic acid (MA) and benzoic acid (BA) from the reline resins [Kooliner (K), New Truliner (N), Ufi Gel hard (U), and Tokuso Rebase Fast (T)] was evaluated. Specimens of each material were divided into two groups: Group C (control) – left untreated; Group WB (water‐bath) – immersion in water at 55 ± 1°C for 10 min. Specimens were placed in artificial saliva at 37 ± 1°C and, after 1‐, 3‐, 5‐, 24‐h and 3‐, 7‐, 14‐, and 30‐day intervals, aliquots were removed and analyzed using high performance liquid chromatography. Data were analyzed by using Wilcoxon, Mann–Whitney or Kruskal–Wallis tests (α = 0.05). At 1 h, the concentration of MA released from U control specimens was higher than those of the other ones, and decreased after 3 h. WB specimens released lower amounts of MA than control specimens only for material U, at the 1‐ and 3‐h periods. For all control specimens, concentrations of leached BA progressively decreased within 5 h and from 24 h to the end. WB specimens released significantly lower amounts of BA than did the control groups. The highest concentration of MA was leached from control specimens of Ufi Gel hard. Water‐bath post‐polymerization treatment caused a significant reduction in elution of BA. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Molecular cloning of mouse glycolate oxidase. High evolutionary conservation and presence of an iron-responsive element-like sequence in the mRNA

Iron regulatory proteins (IRPs) control the synthesis of several proteins in iron metabolism by binding to iron-responsive elements (IREs), a hairpin structure in the untranslated region (UTR) of corresponding mRNAs. Binding of IRPs to IREs in the 5' UTR inhibits translation of ferritin heavy and light chain, erythroid aminolevulinic acid synthase, mitochondrial aconitase, and Drosophila succinate dehydrogenase b, whereas IRP binding to IREs in the 3' UTR of transferrin receptor mRNA prolongs mRNA half-life. To identify new targets of IRPs, we devised a method to enrich IRE-containing mRNAs by using recombinant IRP-1 as an affinity matrix. A cDNA library established from enriched mRNA was screened by an RNA-protein band shift assay. This revealed a novel IRE-like sequence in the 3' UTR of a liver-specific mouse mRNA. The newly identified cDNA codes for a protein with high homology to plant glycolate oxidase (GOX). Recombinant protein expressed in bacteria displayed enzymatic GOX activity. Therefore, this cDNA represents the first vertebrate GOX homologue. The IRE-like sequence in mouse GOX exhibited strong binding to IRPs at room temperature. However, it differs from functional IREs by a mismatch in the middle of its upper stem and did not confer iron-dependent regulation in cells.     

The venotonic drug hydroxyethylrutosiden does not prevent or reduce docetaxel-induced fluid retention: results of a comparative study

PURPOSE: Fluid retention, which includes peripheral edema, ascites, pleural or pericardial effusion, or a combination of these that is sometimes associated with significant weight gain, is one of the most troublesome cumulative side effects of docetaxel. A suggestive observation from the data base available at the manufacturer (Rhone-Poulenc Rorer) was that patients who received venotonic drugs appeared to tolerate more courses of docetaxel. This prompted a comparative study to investigate whether the venotonic drug hydroxyethylrutosiden could reduce or delay docetaxel-related fluid retention. METHODS: A total of 85 patients with metastatic breast cancer who were treated with docetaxel at a dose of 100 mg/m2 with corticoid comedication were allocated to receive either 300 mg hydroxyethylrutosiden given orally four times daily (group A) or no hydroxyethylrutosiden (group B). The end point for analysis was the development of fluid retention of > or = grade 2. RESULTS: Fluid retention of > or = grade 2 was reported in 14 of 42 patients (33%) in group A and in 15 of 43 patients (35%) in group B and occurred after a median of 4 cycles of docetaxel in both groups. Weight gain was similar in groups A and B. CONCLUSION: We conclude that hydroxyethylrutosiden does not reduce or delay the incidence and severity of docetaxel-related fluid retention.