Interactions of iodoperfluorobenzene compounds with gold nanoparticles

Understanding the interactions of small molecules with gold nanoparticles is important for controlling their surface chemistry and, hence, how they can be used in specific applications. The interaction of iodoperfluorobenzene compounds with gold nanoparticles was investigated by UV-Vis difference spectroscopy, surface enhanced Raman spectroscopy (SERS) and Synchrotron X-ray photoelectron spectroscopy (XPS). Results from UV-Vis difference spectroscopy demonstrated that iodoperfluorobenzene compounds undergo charge transfer complexation with gold nanoparticles. SERS of the small molecule–gold nanoparticle adducts provided further evidence for formation of charge transfer complexes, while Synchrotron X-ray photoelectron spectroscopy provided evidence of the binding mechanism. Demonstration of interactions of iodoperfluorobenzene compounds with gold nanoparticles further expands the molecular toolbox that is available for functionalising gold nanoparticles and has significant potential for expanding the scope for generation of hybrid halogen bonded materials.

Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-3,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer?

Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B1*3) and Asn453Ser (CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

PSMA-targeting iron oxide magnetic nanoparticles enhance MRI of preclinical prostate cancer

Aim Evaluate potential of newly-developed, biocompatible iron oxide magnetic nanoparticles (MNPs) conjugated with J591, an antibody to an extracellular epitope of prostate specific membrane antigen (PSMA), to enhance MRI of prostate cancer (PCa). Materials & Methods Specific binding to PSMA by J591-MNP was investigated in vitro. MRI studies were performed on orthotopic tumor-bearing NOD.SCID mice 2h and 24hr after intravenous injection of J591-MNPs, or non-targeting MNPs. Results and Conclusions In vitro, MNPs did not affect PCa cell viability, and conjugation to J591 did not compromise antibody specificity and enhanced cellular iron uptake. In vivo, PSMA-targeting MNPs increased MR contrast of tumors, but not by non-targeting MNPs. This provides proof-of-concept that PSMA-targeting MNPs have potential to enhance MR detection/localization of PCa.,

Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

Health Information Exchange in the wake of ‘big data’ paradigm – the theme is from ‘quality of information to quality of life’

Health Information Exchange (HIE) is an interesting phenomenon. It is a patient centric health and/or medical information management scenario enhanced by integration of Information and Communication Technologies (ICT). While health information systems are repositioning complex system directives, in the wake of the ‘big data’ paradigm, extracting quality information is challenging. It is anticipated that in this talk, ICT enabled healthcare scenarios with big data analytics will be shared. In addition, research and development regarding big data analytics, such as current trends of using these technologies for health care services and critical research challenges when extracting quality of information to improve quality of life will be discussed.

Functional magnetic resonance brain imaging of executive cognitive performance in young first-episode schizophrenia patients and age-matched long-term cannabis users

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like “negative” symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Positive magnetic resonance imaging findings in the asymptomatic wrist

BACKGROUND: Magnetic resonance imaging (MRI) is being increasingly utilized to define pathology and guide treatment in patients presenting with wrist pain. The clinical relevance of MRI identified or confirmed pathology has not been established, and the prevalence of asymptomatic MRI pathology is not known. METHODS: Twenty volunteers with no previous wrist injury or symptoms underwent bilateral MRI wrist studies in this exploratory diagnostic study. The scans were reported by an experienced musculoskeletal radiologist and an experienced wrist surgeon, with a consensus reached on each report. RESULTS: There were 3.15 positive MRI findings per wrist. There were 126 positive findings (range 1-6 per wrist). Sixty-eight ganglia were identified. Eleven ligament tears or perforations were also identified. Increased joint fluid was seen at many sites, most frequently adjacent to the piso-triquetral joint. CONCLUSION: The accuracy of MRI in identifying triangular fibrocartilage complex tears, intercarpal ligament tears and carpal bone osteonecrosis is rapidly being refined. Positive MRI findings are common and may be coincidental in patients with wrist pain. MRI findings need to be correlated closely with clinical examination and history.

Effect of rod-cone interactions on mesopic visual performance mediated by chromatic and luminance pathways

We studied the effect of rod–cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod–cone interactions increase the cone-mediated RTs; (2) the rod–cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (+L-M, S-cone) and luminance (L+M+S) RTs independent of the level of rod activity. The results demonstrate that lateral rod–cone interactions must be considered when deriving mesopic luminous efficiency using RT.