In situ nano- to microscopic imaging and growth mechanism of electrochemical dissolution (e.g., corrosion) of a confined metal surface.

Reactivity in confinement is central to a wide range of applications and systems, yet it is notoriously difficult to probe reactions in confined spaces in real time. Using a modified electrochemical surface forces apparatus (EC-SFA) on confined metallic surfaces, we observe in situ nano- to microscale dissolution and pit formation (qualitatively similar to previous observation on nonmetallic surfaces, e.g., silica) in well-defined geometries in environments relevant to corrosion processes. We follow "crevice corrosion" processes in real time in different pH-neutral NaCl solutions and applied surface potentials of nickel (vs. Ag|AgCl electrode in solution) for the mica-nickel confined interface of total area ∼0.03 mm2 The initial corrosion proceeds as self-catalyzed pitting, visualized by the sudden appearance of circular pits with uniform diameters of 6-7 µm and depth ∼2-3 nm. At concentrations above 10 mM NaCl, pitting is initiated at the outer rim of the confined zone, while below 10 mM NaCl, pitting is initiated inside the confined zone. We compare statistical analysis of growth kinetics and shape evolution of individual nanoscale deep pits with estimates from macroscopic experiments to study initial pit growth and propagation. Our data and experimental techniques reveal a mechanism that suggests initial corrosion results in formation of an aggressive interfacial electrolyte that rapidly accelerates pitting, similar to crack initiation and propagation within the confined area. These results support a general mechanism for nanoscale material degradation and dissolution (e.g., crevice corrosion) of polycrystalline nonnoble metals, alloys, and inorganic materials within confined interfaces.

Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs).

BACKGROUND: No previous prospective trials have been reported with capecitabine and gemcitabine (CAP-GEM) in patients with metastatic thymic epithelial tumors (TETs). We conducted a multicenter study to determine the activity and tolerability of this regimen in pretreated TETs. PATIENTS AND METHODS: A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival. RESULTS: Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1-2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4-17). The 1- and 2-year survival rates were 80% and 67%, respectively. CONCLUSION: We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results.

Toxicological assessment and developmental abnormalities induced by butylparaben and ethylparaben exposure in zebrafish early-life stages.

Toxicological effects of butylparaben (BuP) and ethylparaben (EtP) on zebrafish (Danio rerio) early-life stages are not well established. The present study evaluated, using zebrafish embryos and larvae, the toxicity of BuP and EtP through benchmark dose (BMD) approach. BuP was more toxic than EtP to zebrafish larvae. In fact, Lethal Concentration 50 (LC50) values at 96 h post-fertilization (hpf) for BuP and EtP were 2.34 mg/L and 20.86 mg/L, respectively. Indeed, BMD confidence interval (lower bound (BMDL) - upper bound (BMDU) was 0.91-1.92 mg/L for BuP and 10.8-17.4 mg/L for EtP. Zebrafish embryos exposed to 1 mg/L, 2.5 mg/L of BuP and 5 mg/L, 10 mg/L, 20 mg/L, 30 mg/L of EtP showed several developmental abnormalities and teratological effects compared to negative control. Exposed zebrafish developed reduced heartbeat, reduction in blood circulation, blood stasis, pericardial edema, deformed notochord and misshaped yolk sac. Embryos exposed to the highest concentrations of the chemicals (2.5 mg/L of BuP, 10 mg/L, 20 mg/L and 30 mg/L of EtP) showed the developmental abnormalities at 48 hpf while those treated with 1 mg/L of BuP and 10 mg/L of EtP reported behavioral changes at 72 hpf, including trembling of head, pectoral fins and spinal cord. This research identified the lethal and sublethal effects of BuP and EtP in zebrafish early-life stages and could be helpful to elucidate the developmental pathways of toxicity of parabens.

Embryotoxicity of methylparaben to zebrafish (Danio rerio) early-life stages.

Methylparaben (MeP) is widely used as preservative in personal care products, food commodities and pharmaceuticals due to its antimicrobial properties. Its widespread use resulted in the contamination of aquatic environment and raised concerns about the potential adverse effects on human health, especially in the developing organisms. The aim of the present study was to evaluate the embryotoxicity of MeP in zebrafish early-life stages applying the benchmark-dose (BMD) methodology to Fish embryo acute toxicity (FET) tests-OECD guideline 236. Toxic effects were studied by daily evaluation of lethal endpoints, hatching rate and sublethal alterations. Zebrafish fertilized eggs were exposed until 96 h post fertilization (hpf) to five concentrations of MeP: 1 mg/L, 10 mg/L, 30 mg/L, 60 mg/L and 80 mg/L. The lethal concentration 50 (LC 50) was 72.67 mg/L. Indeed, BMD confidence interval (lower bound, BMDL-upper bound, BMDU) was 40.8-57.4 mg/L for lethal endpoints and 16-26.5 mg/L for toxicity index, that includes both lethal and sublethal alterations. Zebrafish embryos exposed to MeP developed sublethal alterations including pericardial edema, yolk edema, blood stasis, reduction in blood circulation, reduced heartbeat and notochord curvature. The number of embryos exposed to the highest concentrations of MeP that reported sublethal alterations increased between 24hpf and 48 hpf-72 hpf-96 hpf. Only zebrafish larvae treated with 30 mg/L of MeP showed behavioural changes. This study highlighted the detrimental effects of MeP on zebrafish early-life stages with attention to its developmental toxicity.

Quantitative analysis of oxysterols in zebrafish embryos by HPLC-MS/MS.

Zebrafish is an in vivo model used in toxicology to estimate the effects of xenobiotics and their teratogenic consequences. The knowledge of the oxysterols profile in zebrafish, during early embryonic stages, provides important information on the role and biological function of these molecules. This work reports the development and validation of a LC-MS/MS method for the determination of 7 different oxysterols in zebrafish embryos. Sample was treated with a combination of liquid/liquid extraction (LLE) followed by micro solid phase extraction (µSPE) clean-up in order to remove matrix interference and obtain a suitable enrichment factor of the analytes. The method was validated on 2 different embryos growing stages, 3-4 and 24 h post fertilization (hpf), as slight differences in terms of recovery and matrix effect were shown. The validation results provided good accuracy (bias ≤17%; 20% at LOQ) and repeatability (≤15%; ≤19% at LOQ), with low LOQs in the range 22 and 65 pg on 100 embryos sample, without any analyte derivatization, demonstrating the suitability of this analytical method as a useful tool to understand the correlation between oxysterols profile and developmental abnormalities induced by xenobiotic exposure.

The Effect of Water and Confinement on Self-Assembly of Imidazolium Based Ionic Liquids at Mica Interfaces.

Tuning chemical structure and molecular layering of ionic liquids (IL) at solid interfaces offers leverage to tailor performance of ILs in applications such as super-capacitors, catalysis or lubrication. Recent experimental interpretations suggest that ILs containing cations with long hydrophobic tails form well-ordered bilayers at interfaces. Here we demonstrate that interfacial bilayer formation is not an intrinsic quality of hydrophobic ILs. In contrast, bilayer formation is triggered by boundary conditions including confinement, surface charging and humidity present in the IL. Therefore, we performed force versus distance profiles using atomic force microscopy and the surface forces apparatus. Our results support models of disperse low-density bilayer formation in confined situations, at high surface charging and/or in the presence of water. Conversely, interfacial structuring of long-chain ILs in dry environments and at low surface charging is disordered and dominated by bulk structuring. Our results demonstrate that boundary conditions such as charging, confinement and doping by impurities have decisive influence on structure formation of ILs at interfaces. As such, these results have important implications for understanding the behavior of solid/IL interfaces as they significantly extend previous interpretations.

Low-dose dopamine induces early recovery of recombinant interleukin-2--impaired renal function.

Recombinant interleukin-2 (rIL-2) can produce impairment of renal function with hypotension, fluid retention, elevated blood urea nitrogen, oliguria and low fractional sodium excretion; these side-effects are a common cause of reduction or interruption of rIL-2 infusion. The aim of this study was to investigate the control and treatment of renal toxicity induced by rIL-2 therapy. Here we show that dopamine, at a low dose of 2 micrograms/kg/min, completely prevented renal toxicity induced by rIL-2. While continuing rIL-2 therapy, 24-h continuous infusion of low-dose dopamine produced a rapid normalisation of urine output and a significant decrease in serum creatinine levels and body weight (P < 0.01), with an early and complete recovery of the rIL-2--impaired renal function: mean recovery time of renal function in patients treated with dopamine was significantly lower (P < 0.05) than in nontreated patients (4.8 days vs. 10 days, respectively).

Probing for nasolacrimal duct obstruction with intravenous propofol sedation.

BACKGROUND: Nasolacrimal duct obstruction occurs in 5% to 6% of neonates. Many studies advocate the probing of nasolacrimal duct obstruction under general inhalational anesthesia in patients at a late age (12 to 13 months) because a high percentage will resolve spontaneously. Others support early surgical intervention in patients aged younger than 6 to 9 months without anesthesia. We present late nasolacrimal duct probing under intravenous propofol sedation as an alternative approach to the treatment of nasolacrimal duct obstruction with a decrease in cost and time compared with probing under general inhalational anesthesia. METHODS: We made a retrospective review of patient charts of children who underwent nasolacrimal duct probing with intravenous propofol sedation from April 1996 to September 1997. Procedure time and cost of procedure were compared for patients who had probings under propofol sedation to patients who had probings under general anesthesia. RESULTS: A total of 22 patients (31 eyes) underwent nasolacrimal duct probing with propofol sedation; the patients' ages ranged from 11.5 to 39 months (average age, 17.8 months). Twenty-six (84%) of 31 eyes had resolution of the symptoms. The average total time for procedure under propofol sedation was 10.5 minutes, compared with 43.6 minutes under general inhalational anesthesia. The average total recovery time under propofol sedation was 13.6 minutes, compared with 121.1 minutes with general inhalational anesthesia. The cost of probing under propofol sedation was one third less than the cost of probing under general inhalational anesthesia. DISCUSSION: Late probing for nasolacrimal duct obstruction under intravenous propofol sedation is comparable in efficacy to late probing under general inhalational anesthesia with a shorter time for the procedure and decreased expense.

An audit of adverse events in children sedated with chloral hydrate or propofol during imaging studies.

We examined records of sedations provided by the paediatric anaesthesiology staff for 455 children (ages 1 mo-17 yr) undergoing MRI or CT scans at our institution over a twelve-month period with regard to the monitoring of adverse events: excessive sedation, agitation, vomiting, hypoxaemia, and major airway compromise. One hundred-and-thirty-one patients (29%) received chloral hydrate; 324 patients (71%) received propofol. All patients were monitored with continuous noninvasive pulse oximetry and received supplemental oxygen via nasal cannulae. Of the patients who received chloral hydrate, 64 (49%) were over one year of age; of the patients who received propofol, 318 (98%) were one year of age or older. In the chloral hydrate group, 23 patients (19%) were deemed excessively sedated and four patients (3%) were agitated; no patients in the propofol group experienced any of the adverse outcomes reviewed. Furthermore, no patients in either group had significant airway compromise and none was admitted to the hospital as a result of the sedation.