Optimising the management of dysplastic lesions in the oesophagus with photodynamic therapy

The outcome of patients suffering from adeno and squamous carcinoma of the oesophagus remains poor. In the west, the incidence of adenocarcinoma has increased dramatically, with most cases occurring in association with Barrett's oesophagus (BE). Both adeno and squamous carcinoma are believed to progress through worsening degrees of dysplasia. This thesis assesses the role of Elastic Scattering Spectroscopy (ESS) as an objective diagnostic test for dysplasia and Photodynamic Therapy (PDT) with 5-aminolevulinic acid (ALA) as a less invasive treatment option. It also looks for a better understanding of the factors influencing mucosal healing after PDT. Using ESS, the sensitivity and specificity was 83% for distinguishing HGD/cancer from LGD/non dysplastic BE. Low dose ALA (30mg/kg) PDT eradicated 38% of HGD in BE compared with 67% eradication with a higher dose (60mg/kg). The higher dose also decreased the length of BE. In a study comparing red with green light (fixed light doses) for treating HGD, at 30 mg/kg ALA, 63% and 13 % of patients were clear of HGD with red and green laser respectively. At 60 mg/kg, the corresponding figures were 78% and 33% for the same light dose. 5 of 5 patients with LGD in BE and 4 of 5 patients with HGD in squamous mucosa had their dysplasia eradicated with ALA PDT. Successful PDT involves healing by regeneration of normal squamous mucosa. My in vitro studies created a PDT wound model using malignant oesophageal cell lines to assess the role of different cytokines in healing. Keratinocyte Growth Factor (KGF) was found to promote wound healing after PDT and significantly encouraged (p 0.001) the development of squamous cell lines. In conclusion: 1. ESS can differentiate dysplasia and early cancer from non-dysplastic and normal mucosa (sensitivity and specificity 83%). 2. PDT using high dose (60mg/kg) ALA (but not low dose) is effective in eradicating HGD in BE using red light. 3. The cytokine, KGF may promote healing with squamous mucosa after PDT. 4. Larger scale clinical trials are now required to confirm these results

A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

<p>Abstracts</p> <p>Background</p> <p>Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults.</p> <p>Methods/Design</p> <p>We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale.</p> <p>Discussion</p> <p>This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01478009">NCT01478009</a>.</p

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Production of Coumaroylserotonin and Feruloylserotonin in Transgenic Rice Expressing Pepper Hydroxycinnamoyl-Coenzyme A:Serotonin N-(Hydroxycinnamoyl)transferase

Transgenic rice (Oryza sativa) plants were engineered to express a N-(hydroxycinnamoyl)transferase from pepper (Capsicum annuum), which has been shown to have hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase activity, a key enzyme in the synthesis of hydroxycinnamic acid amides, under the control of constitutive maize (Zea mays) ubiquitin promoter. The transgenic rice plants require foliar application of amines to support synthesis of hydroxycinnamic acid amides, suggestive of limiting amine substrates in rice shoots. In addition, when T(2) homozygous transgenic rice plants were grown in the presence of amines or phenolic acids, two novel compounds were exclusively identified in the leaves of the transgenic plants. These compounds eluted earlier than p-coumaroyltyramine and feruloyltyramine during HPLC chromatography and were identified as p-coumaroylserotonin and feruloylserotonin by liquid chromatography/mass spectrometry and other methods. To test whether the unpredicted production of serotonin derivatives is associated with the pepper N-(hydroxycinnamoyl)transferase, the substrate specificity of the pepper enzyme was analyzed again. Purified recombinant pepper N-(hydroxycinnamoyl)transferase exhibited a serotonin N-hydroxycinnamoyltransferase (SHT) activity, synthesized p-coumaroylserotonin and feruloylserotonin in vitro, and demonstrated a low K(m) for serotonin. SHT activity was inhibited by 10 to 50 mm tyramine. In addition, SHT activity was predominantly found in the root tissues of wild-type rice in parallel with the synthesis of serotonin derivatives, suggesting that serotonin derivatives are synthesized in the root of rice. This is the first report of SHT activity and the first demonstration, to our knowledge, that serotonin derivatives can be overproduced in vivo in transgenic rice plants that express serotonin N-(hydroxycinnamoyl)transferase