Soil copper uptake by land snails: A semi-field experiment with juvenile Cantareus aspersus snails.

There is currently limited scientific evidence linking soil copper and land snails, although these invertebrates are important players in terrestrial ecosystems. In the present study, Cantareus aspersus juveniles, were exposed in two successive phases of 30 days each, to soil spiked with increasing concentrations of copper sulfate. Copper concentrated preferentially and in a dose-dependent manner in the hepatopancreas. In the case of specimens previously exposed to Cu-spiked soils, Cu retention kinetics were independent from the effects of a new exposure event. There was no effect on shell growth, but significant mortality was observed at 60 days. The no observed effect concentration and the lowest observed effect concentration for mortality in snails, were ˜ 41 and 54 mg, respectively, per grams dry weight in the hepatopancreas. The results demonstrate, for the first time, that terrestrial gastropods can accumulate soil Cu autonomously from dietary uptake.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment.

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH)2 without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd2+ ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd2+ ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd2+ from sources such as cigarette smoke.

Synthesis of Co3O4 nanoparticles with block and sphere morphology, and investigation into the influence of morphology on biological toxicity.

In the present study, cobalt oxide (Co3O4) magnetic nanoparticles with block and sphere morphologies were synthesized using various surfactants, and the toxicity of the particles was analyzed by monitoring biomarkers of nanoparticle toxicity in zebrafish. The use of tartarate as a surfactant produced highly crystalline blocks of Co3O4 nanoparticles with pores on the sides, whereas citrate lead to the formation of nanoparticles with a spherical morphology. Co3O4 structure, crystallinity, size and morphology were studied using X-ray diffractogram and field emission scanning electron microscopy. Following an increase in nanoparticle concentration from 1 to 200 ppm, there was a corresponding increase in nitric oxide (NO) generation, induced by both types of nanoparticles [Co3O4-NP-B (block), r=0.953; Co3O4-NP-S (sphere), r=1.140]. Comparative analyses indicated that both types of nanoparticle produced significant stimulation at ≥5 ppm (P<0.05) compared with a control. Upon analyzing the effect of nanoparticle morphology on NO generation, it was observed that Co3O4-NP-S was more effective compared with Co3O4-NP-B (5 and 100 ppm, P<0.05; 200 ppm, P<0.01). Exposure to both types of nanoparticles produced reduction in liver glutathione (GSH) activity with corresponding increase in dose (Co3O4-NP-B, r=-0.359; Co3O4-NP-S, r=-0.429). However, subsequent analyses indicated that Co3O4-NP-B was more potent in inhibiting liver GSH activity compared with Co3O4-NP-S. Co3O4-NP-B proved to be toxic at 5 ppm (P<0.05) and GSH activity was almost completely inhibited at 200 ppm. A similar toxicity was observed with both types of Co3O4-NPs against brain levels of acetylcholinesterase (AChE; Co3O4-NP-B, r=-0.180; Co3O4-NP-S, r=-0.230), indicating the ability of synthesized Co3O4-NPs to cross the blood-brain barrier and produce neuronal toxicity. Co3O4-NP-B showed increased inhibition of brain AChE activity compared with Co3O4-NP-S (1,5, and 10 ppm, P<0.05; 50, 100 and 200 ppm, P<0.01). These results suggested that the morphology of nanoparticle and surface area contribute to toxicity, which may have implications for their biological application.

Patient preference and willingness-to-pay for Humalog Mix25 relative to Humulin 30/70: a multicountry application of a discrete choice experiment.

OBJECTIVES: To assess preference and willingness-to-pay (WTP) for the insulin mixture Humalog Mix25 relative to Humulin 30/70, from the patients' perspective, the relative importance of individual treatment attributes was also determined. Differences among five European countries were investigated. METHODS: Two hundred and ninety patients with type 2 diabetes were recruited from five European countries. Of these, 235 were suitable for inclusion in the analysis. Their mean age was 51.3 years and, on average, patients had had diabetes for 11 years. A discrete-choice conjoint analysis was conducted using face-to-face interviews. Treatment attributes, such as timing of injections around meals, 2-hour postprandial control, effect of prandial dosing, frequency of nocturnal hypoglycemia, and cost, and levels were derived after a systematic review of all published comparative clinical trial data. Meta-analyses were undertaken where appropriate. RESULTS: Ninety percent (95% CI 86-93%) of patients would choose Humalog Mix25 over Humulin 30/70, at the same cost. On average, European subjects were willing to pay 111 euros per month more for Humalog Mix25 (95% CI 86.71-156.91 euros). The primary driver was the reduced risk of nocturnal hypoglycemic events, contributing 49% of WTP. The convenience of dosing immediately before the meal contributed 37%. Preference results were similar in all five countries, although WTP and sensitivity to increasing cost both varied. CONCLUSIONS: Patients in all countries showed a preference and WTP for Humalog Mix25 over Humulin 30/70. The main drivers of patient WTP may be of interest to pharmaceutical prescribers, manufacturers, and reimbursement agencies.

Retrospective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in Europe.

In two recent randomised trials, gemcitabine plus cisplatin (Gem/Cis) was found to be at least as effective as vinorelbine plus cisplatin (Vin/Cis), paclitaxel plus cisplatin (Pac/Cis), paclitaxel plus carboplatin (Pac/Carbo), or docetaxel plus cisplatin (Doc/Cis) in patients with advanced non-small cell lung cancer (NSCLC). In cost-minimisation analyses of these studies from the perspectives of the national health services of five European countries (France, Germany, Italy, Spain, UK), Gem/Cis was associated with lower average treatment-related costs than Vin/Cis, Pac/Cis, and Pac/Carbo, and similar or lower costs than Doc/Cis. The incremental cost savings per patient of Gem/Cis compared to Vin/Cis ranged from 827 Euro to 2055 Euro per patient and from 1616 Euro to 5342 Euro compared to the paclitaxel-containing regimens. Overall, results were generally similar between countries, and were robust to univariate sensitivity analyses. Although differences in healthcare systems mean that the results may not be generalisable to all countries/settings, these results provide an economic rationale for the use of Gem/Cis as a first-line treatment option in Europe for patients with NSCLC.

Cost-utility analysis of the GC versus MVAC regimens for the treatment of locally advanced or metastatic bladder cancer.

A cost-utility analysis was conducted to compare the gemcitabine (Gemzar)/cisplatin and methotrexate/vinblastine(Velban)/doxorubicin (Doxil)/cisplatin regimens in the treatment of locally advanced or metastatic bladder cancer. The analysis combined the results of a cost analysis of a head-to-head Phase III clinical trial with those from a cross-sectional utility study. The analysis was performed from the perspective of the National Health Service in England and Wales. Medical resource use was obtained from the clinical trial database, from which patient-level cost streams were estimated for each treatment group. Unit costs for each resource utilization component were sought from the latest UK cost sources available at the time of analysis (2001). The distribution of the mean total and incremental costs for each group was simulated via bias-adjusted bootstrapping. Time trade-off utilities were derived from the utility study, which aimed to value the superior toxicity profile associated with gemcitabine/cisplatin, given comparable efficacy, in a discrete choice model assessing toxicity attributes and risks. The mean incremental cost of gemcitabine/cisplatin over methotrexate/vinblastine/doxorubicin/cisplatin was estimated to be approximately pound sterling 2976 per patient, based on a mean of 4.65 cycles per patient treated with gemcitabine/cisplatin compared with a mean of 3.92 cycles per methotrexate/vinblastine/doxorubicin/cisplatin patient. When combined with the utility estimates, this resulted in an incremental cost-effectiveness ratio of approximately pound sterling 22,925 per quality-adjusted life year gained associated with the choice of gemcitabine/cisplatin over methotrexate/vinblastine/doxorubicin/cisplatin. A 95% confidence interval for the incremental cost-effectiveness ratio was calculated to range from pound sterling 12,911 to 33,589 per quality-adjusted life year gained. The incremental cost of gemcitabine/cisplatin is primarily due to the direct costs of chemotherapy given minimal cost offsets. However, an incremental cost per quality-adjusted life year ratio in the range of pound sterling 20,000-30,000 per quality-adjusted life year gained suggested that the regimen is reasonable value for money in England and Wales.