Electrochemical detection of dopamine and cytochrome c at a nanostructured gold electrode

A nanostructured gold surface consisting of closely packed outwardly growing spikes is investigated for the electrochemical detection of dopamine and cytochrome c. A significant electrocatalytic effect for the electrooxidation of both dopamine and ascorbic acid at the nanostructured electrode was found due to the presence of surface active sites which allowed the detection of dopamine in the presence of excess ascorbic acid to be achieved by differential pulse voltammetry. By simple modification with a layer of Nafion, the enhanced electrocatalytic properties of the nanostructured surface was maintained while increasing the selectivity of dopamine detection in the presence of interfering species such as excess ascorbic and uric acids. Also, upon modification of the nanostructured surface with a monolayer of cysteine, the electrochemical response of immobilised cytochrome c in two distinct conformations was observed. This opens up the possibility of using such a nanostructured surface for the characterisation of other biomolecules and in bio-electroanalytical applications.

The facile formation of silver dendritic structures in the absence of surfactants and their electrochemical and SERS properties

In this work a simple approach to the creation of highly dispersed electrocatalytically active silver microstructured dendrites on indium tin oxide in the absence of any surface modification or surfactant is presented. It is found that the addition of low concentrations of supporting electrolyte to the AgNO3 solution dramatically influences the morphology of electrodeposited silver which is independent of both the anion and the cation employed. The silver dendrites are characterized by SEM, XRD, XPS as well as by cyclic voltammetry under alkaline conditions. It is found that the surface oxide formation and removal processes are significantly influenced by the microstructured morphology of the silver electrodeposits compared to a smooth macrosized silver electrode. The facile formation of dendritic silver microstructures is also shown to be beneficial for the electrocatalytic oxidation of both formaldehyde and hydrazine and oxygen reduction. The formation of a continuous film of dendritic silver is also investigated for its SERS activity where the connectivity between the individual dendrites is found to be particularly important.

Monitoring cuprous ion transport by scanning electrochemical microscopy during the course of copper electrodeposition

Scanning electrochemical microscopy (SECM), in the substrate generation–tip collection (SG-TC) mode, has been used to detect the cuprous ion intermediate formed during the course of electrodeposition of Cu metal from aqueous solution. Addition of chloride is confirmed to strongly stabilize the ion in aqueous solution and enhance the rate of Cu electrodeposition. This SECM method in the SG-TC mode offers an alternative to the rotating ring disk electrode (RRDE) technique for in situ studies on the effect of plating bath additives in metal electrodeposition. An attractive feature of the SECM relative to the RRDE method is that it allows qualitative aspects of the electrodeposition process to be studied in close proximity to the substrate in a simple and direct fashion using an inexpensive probe, and without the need for forced convection.

Scanning electrochemical microscopy study of the solid--solid interconversion of TCNQ to phase I and phase II CuTCNQ

The reduction of 7,7,8,8-tetracyanoquinodimethane (TCNQ) crystals attached to a glassy carbon electrode in the presence of Cu2+(aq) to form CuTCNQ(s) has been investigated using scanning electrochemical microscopy in the substrate generation tip collection mode and shown to involve a generation of soluble TCNQ−(aq). The subsequent oxidation of CuTCNQ does not involve simple expulsion of Cu+ into solution but a soluble complex attributed to Cu2+TCNQ−(aq). Mechanistic insights relative to the electrochemical conversion of CuTCNQ phase I into phase II by repetitive cycling of potential and electrochemical formation of KTCNQ have also been established

Electrochemical formation of porous copper 7, 7, 8, 8-tetracyanoquinodimethane and copper 2, 3, 5, 6-tetrafluoro-7, 7, 8, 8-tetracyanoquinodimethane honeycomb surfaces with superhydrophobic properties

The electrochemical formation of highly porous CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane) and CuTCNQF4 (TCNQF4 = 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) materials was undertaken via the spontaneous redox reaction between a porous copper template, created using a hydrogen bubbling template technique, and an acetonitrile solution containing TCNQ or TCNQF4. It was found that activation of the surface via vigorous hydrogen evolution that occurs during porous copper deposition and TCNQ mass transport being hindered through the porous network of the copper template influenced the growth of CuTCNQ and CuTCNQF4. This approach resulted in the fabrication of a honeycomb layered type structure where the internal walls consist of very fine crystalline needles or spikes. This combination of microscopic and nanoscopic roughness was found to be extremely beneficial for anti-wetting properties where superhydrophobic materials with contact angles as high as 177° were created. Given that CuTCNQ and CuTCNQF4 have shown potential as molecular based electronic materials in the area of switching and field emission, the creation of a surface that is moisture resistant may be of applied interest.

A combined scanning electron micrograph and electrochemical study of the effect of chemical interaction on the cyclability of lithium electrodes in an ionic liquid electrolyte

The effect of storage time on the cyclability of lithium electrodes in an ionic liquid electrolyte, namely 0.5 m LiBF4 in N-methyl-N-propyl pyrrolidinium bis(fluorosulfonyl)imide, [C3mpyr+][FSI–], was investigated. A chemical interaction was observed which is time dependent and results in a morphology change of the Li surface due to build up of passivation products over a 12-day period. The formation of this layer significantly impacts on the Li electrode resistance before cycling and the charging/discharging process for symmetrical Li|0.5 m LiBF4 in [C3mpyr+][FSI–]|Li coin cells. Indeed it was found that introducing a rest period between cycling, and thereby allowing the chemical interaction between the Li electrode and electrolyte to take place, also impacted on the charging/discharging process. For all Li surface treatments the electrode resistance decreased after cycling and was due to significant structural rearrangement of the surface layer. These results suggest that careful electrode pretreatment in a real battery system will be required before operation.

Aqueous phase synthesis of copper nanoparticles : a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems

We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii. This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase. Electrochemical analysis of bacterial cells exposed to Cu2+ ions provides new insights into the mechanistic aspect of Cu2+ ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction. The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.

The electrochemical corrosion behaviour of quaternary gold alloys when exposed to 3.5% NaCl solution

Lower carat gold alloys, specifically 9 carat gold alloys, containing less than 40 % gold, and alloying additions of silver, copper and zinc, are commonly used in many jewellery applications, to offset high costs and poor mechanical properties associated with pure gold. While gold is considered to be chemically inert, the presence of active alloying additions raises concerns about certain forms of corrosion, particularly selective dissolution of these alloys. The purpose of this study was to systematically study the corrosion behaviour of a series of quaternary gold–silver–copper–zinc alloys using dc potentiodynamic scanning in saline (3.5 % NaCl) environment. Full anodic/cathodic scans were conducted to determine the overall corrosion characteristics of the alloy, followed by selective anodic scans and subsequent morphological and compositional analysis of the alloy surface and corroding media to determine the extent of selective dissolution. Varying degrees of selective dissolution and associated corrosion rates were observed after anodic polarisation in 3.5 % NaCl, depending on the alloy composition. The corrosion behaviour of the alloys was determined by the extent of anodic reactions which induce (1) formation of oxide scales on the alloy surface and or (2) dissolution of Zn and Cu species. In general, the improved corrosion characteristics of alloy #3 was attributed to the composition of Zn/Cu in the alloy and thus favourable microstructure promoting the formation of protective oxide/chloride scales and reducing the extent of Cu and Zn dissolution.

Surgical resection for non-small cell lung cancer : clinical features and outcomes for a consecutive series at an Irish tertiary referral centre

Background: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. Methods: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. Results: A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. Conclusion: We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres. © 2012 Royal Academy of Medicine in Ireland.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer

Purpose: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. Patients and Methods: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. Results: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. Conclusion: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC. © 2005 by American Society of Clinical Oncology.

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/ cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer : a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)

Background: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients and methods: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m 2, carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2 and cisplatin 50 mg/m 2 or mitomycin 6 mg/ m 2, vinblastine 6 mg/m 2 and cisplatin 50 mg/m 2, respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. Results: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. Conclusions: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained. © 2006 European Society for Medical Oncology.

Quantifying alterations in cell migration : tracking fluorescently-tagged migrating cells by FACs and live-imaging

Cell migration is fundamental to many different physiological processes including embryonic development, inflammation and wound healing. Given the range and importance cell migration plays a number of assays have been developed to measure different aspects of cell migration. Here we describe two different methods to analyze cell migration. The first method analyzes the migration of fluorescently tagged cells using Boyden chambers and FACs and the second looks at migration properties using time-lapse microscopy.