Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia

Weight loss in advanced cancer patients is refractory to conventional nutritional support. This may be due to metabolic changes mediated by proinflammatory cytokines, hormones, and tumor-derived products. We previously showed that a nutritional supplement enriched with fish oil will reverse weight loss in patients with pancreatic cancer cachexia. The present study examines the effect of this supplement on a number of mediators thought to play a role in cancer cachexia. Twenty weight-losing patients with pancreatic cancer were asked to consume a nutritional supplement providing 600 kcal and 2 g of eicosapentaenoic acid per day. At baseline and after 3 wk, patients were weighed and samples were collected to measure serum concentrations of interleukin (IL)-6 and its soluble receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin, peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor necrosis factor, and urinary excretion of proteolysis inducing factor. After 3 wk of consumption of the fish oil-enriched nutritional supplement, there was a significant fall in production of IL-6 (from median 16.5 to 13.7 ng/ml, P = 0.015), a rise in serum insulin concentration (from 3.3 to 5.0 mU/l, P = 0.0064), a fall in the cortisol-to-insulin ratio (P = 0.0084), and a fall in the proportion of patients excreting proteolysis inducing factor (from 88% to 40%, P = 0.008). These changes occurred in association with weight gain (median 1 kg, P = 0.024). Various mediators of catabolism in cachexia are modulated by administration of a fish oil-enriched nutritional supplement in pancreatic cancer patients. This may account for the reversal of weight loss in patients consuming this supplement.

Fluorescent probe:complexation of Fe3+ with the myo-inositol 1,2,3-trisphosphate motif

Natural myo-inositol phosphate antioxidants containing the 1,2,3-trisphosphate motif bind Fe3+ in the unstable penta-axial conformation.

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection.

Synthesis of a PbTx-2 photoaffinity and fluorescent probe and an alternative synthetic route to photoaffinity probes

A natural phenomenon characterized by dense aggregations of unicellular photosynthetic marine organisms has been termed colloquially as red tides because of the vivid discoloration of the water. The dinoflagellate Karenia brevis is the cause of the Florida red tide bloom. K. brevis produces the brevetoxins, a potent suite of neurotoxins responsible for substantial amounts of marine mammal and fish mortalities. When consumed by humans, the toxin causes Neurotoxic Shellfish Poisoning (NSP). The native function of brevetoxin within the organism has remained mysterious since its discovery. There is a need to identify factors which contribute to and regulate toxin production within K. brevis. These toxins are produced and retained within the cell implicating a significant cellular role for their presence. Localization of brevetoxin and identification of a native receptor may provide insight into its native role as well as other polyether ladder type toxins such as the ciguatoxins, maitotoxins, and yessotoxins. In higher organisms these polyether ladder molecules bind to transmembrane proteins with high affinity. We anticipated the native brevetoxin receptor would also be a transmembrane protein. Photoaffinity labeling has become increasingly popular for identifying ligand receptors. By attaching ligands to these photophors, one is able to activate the molecule after the ligand binds to its receptor to obtain a permanent linkage between the two. Subsequent purification provides the protein with the ligand directly attached. A molecule that is capable of fluorescence is a fluorophore, which upon excitation is capable of re-emitting light. Fluorescent labeling uses fluorophores by attaching them covalently to biologically active compounds. The synthesis of a brevetoxin photoaffinity probe and its application in identifying a native brevetoxin receptor will be described. The preparation of a fluorescent derivative of brevetoxin will be described and its use in localizing the toxin to an organelle within K. brevis. In addition, the general utility of a synthesized photoaffinity label with other toxins having similar functionality will be described. An alternative synthetic approach to a general photoaffinity label will also be discussed whose goal was to accelerate the preparation and improve the overall synthetic yields of a multifunctional label.

Seawater carbonate chemistry and biological processes during experiments with clownfish Amphiprion percula, 2009

The persistence of most coastal marine species depends on larvae finding suitable adult habitat at the end of an offshore dispersive stage that can last weeks or months. We tested the effects that ocean acidification from elevated levels of atmospheric carbon dioxide (CO2) could have on the ability of larvae to detect olfactory cues from adult habitats. Larval clownfish reared in control seawater (pH 8.15) discriminated between a range of cues that could help them locate reef habitat and suitable settlement sites. This discriminatory ability was disrupted when larvae were reared in conditions simulating CO2-induced ocean acidification. Larvae became strongly attracted to olfactory stimuli they normally avoided when reared at levels of ocean pH that could occur ca. 2100 (pH 7.8) and they no longer responded to any olfactory cues when reared at pH levels (pH 7.6) that might be attained later next century on a business-as-usual carbon-dioxide emissions trajectory. If acidification continues unabated, the impairment of sensory ability will reduce population sustainability of many marine species, with potentially profound consequences for marine diversity.

Plasticity varies with boldness in a weakly-electric fish

The expression of animal personality is indicated by patterns of consistency in  individual behaviour. Often, the differences exhibited between individuals are consistent across situations. However, between some situations, this can be biased by variable levels of individual plasticity. The interaction between individual plasticity and animal personality can be illustrated by examining situation-sensitive personality traits such as boldness (i.e. risk-taking and exploration tendency). For the weakly electric fish Gnathonemus petersii, light condition is a major factor influencing behaviour. Adapted to navigate in low-light conditions, this species chooses to be more active in dark environments where risk from visual predators is lower. However, G. petersii also exhibit individual differences in their degree of behavioural change from light to dark. The present study, therefore, aims to  examine if an increase of motivation to explore in the safety of the dark, not only affects mean levels of boldness, but also the variation between individuals, as a result of differences  in individual plasticity.  Results: Boldness was consistent between a novel-object and a novel-environment situation in bright light. However, no consistency in boldness was noted between a bright (risky) and a  dark (safe) novel environment. Furthermore, there was a negative association between boldness and the degree of change across novel environments, with shier individuals  exhibiting greater behavioural plasticity.  Conclusions: This study highlights that individual plasticity can vary with personality. In  addition, the effect of light suggests that variation in boldness is situation specific. Finally,  there appears to be a trade-off between personality and individual plasticity with shy but  plastic individuals minimizing costs when perceiving risk and bold but stable individuals  consistently maximizing rewards, which can be maladaptive.

‘Probing with the prototype’: using a prototype e-participation platform as a digital cultural probe to investigate youth engagement with the environment

This study describes how we used a prototype e-participation plat-form as a digital cultural probe to investigate youth motivation and engagement strategies. This is a novel way of considering digital cultural probes which can contribute to the better creation of e-participation platforms. This probe has been conducted as part of the research project STEP which aims at creating an e-participation platform to engage young European Citizens in environmental decision making. Our probe technique has given an insight into the environ-mental issues concerning young people across Europe as well as possible strat-egies for encouraging participation. How the e-participation platform can be utilised to support youth engagement through opportunities for social interac-tion and leadership is discussed. This study leads to a better understanding of how young people can co-operate with each other to provide collective intelli-gence and how this knowledge could contribute to effective e-participation of young people.

Studies on Mahshahr Creeks macrobenthos with emphasis on their importance in fish feeding

To study the macrobenthic community at Mahshahr creek four Creeks namely Bihad, Doragh, Ghazaleh and Ghanam were chosen. Sampling was conducted on bimonthly basis and carried out from August 1996 to June 1997, 216 sediment samples were collected from 12 stations using 0.1 m^2 Van Veen Grab, The stations were located at the mouth, middle and the end of each Creek. In situ measurements of temperature pH, DO and salinity were done using different sensors. The samples for the measurements of TOM, grain size were collected and analysed in vitro. The results indicate spatial and temporal heterogeneity in the structure of macro faunal assemblages of the creeks. A total of 12 macrofaunal groups were identified within the study area. Amphipods were the most dominant group (43%) followed by polychaetes (42%), copepods (3.5%), tanaids (3.1%) and other groups (8.4%). The range for the numerical abundance of macrobenthos was between 12583 to 3648 individual per m2 and the variation was done to different bottom texture the variable environment conditions governing the different parts of each creek as well as within creeks. Application of diversity indices (Shannon H and Simpson indices) on the dominant macrobenthic assemblages (crustaceans & polychaetes) was varied between 1 to 2.5 being higher in Bihad and Ghanarn and much reduced Shannon H index or a higher Simpson in Ghazaleh. Probably brought about activities in this creek. Gut content analysis of four species of fish showed that the main food items consist of Crab, Shrimps and other crustacean species, The secondary production of macrobenthic fauna and hence a fish production were assessed. To do this first the production of most dominant species Apseudes sp. was computed through Cohort analysis. The total macrobenthic production was estimated and from this fish production was computed. The macrobenthic and fish secondary productions were 24300 tons/year) and 24300 (tons/year) respectively. These values were lower than those with similar areas in the Indian Ocean.

Interaction between mercury (Hg), arsenic (As) and selenium (Se) affects the activity of glutathione S-transferase in breast milk: possible relationship with fish and shellfish intake

Breast milk is regarded as an ideal source of nutrients for the growth and development of neonates, but it can also be a potential source of pollutants. Mothers can be exposed to different contaminants as a result of their lifestyle and environmental pollution. Mercury (Hg) and arsenic (As) could adversely affect the development of fetal and neonatal nervous system. Some fish and shellfish are rich in selenium (Se), an essential trace element that forms part of several enzymes related to the detoxification process, including glutathione S-transferase (GST). The goal of this study was to determine the interaction between Hg, As and Se and analyze its effect on the activity of GST in breast milk. Milk samples were collected from women between day 7 and 10 postpartum. The GST activity was determined spectrophotometrically; total Hg, As and Se concentrations were measured by atomic absorption spectrometry. To explain the possible association of Hg, As and Se concentrations with GST activity in breast milk, generalized linear models were constructed. The model explained 44% of the GST activity measured in breast milk. The GLM suggests that GST activity was positively correlated with Hg, As and Se concentrations. The activity of the enzyme was also explained by the frequency of consumption of marine fish and shellfish in the diet of the breastfeeding women.

On the interaction of bovine serum albumin with ionic surfactants: Temperature induced EPR changes of a maleimide nitroxide reflect local protein dynamics and probe solvent accessibility

The interaction of bovine serum albumin (BSA) with the ionic surfactants sodium dodecylsulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) was studied by electron paramagnetic resonance (EPR) spectroscopy of spin label covalently bound to the single free thiol group of the protein. EPR spectra simulation allows to monitor the protein dynamics at the labeling site and to estimate the changes in standard Gibbs free energy, enthalpy and entropy for transferring the nitroxide side chain from the more motionally restricted to the less restricted component. Whereas SDS and CTAC showed similar increases in the dynamics of the protein backbone for all measured concentrations. HPS presented a smaller effect at concentrations above 1.5 mM. At 10 mM of surfactants and 0.15 mM BSA, the standard Gibbs free energy change was consistent with protein backbone conformations more expanded and exposed to the solvent as compared to the native protein, but with a less pronounced effect for HPS. In the presence of the surfactants, the enthalpy change, related to the energy required to dissociate the nitroxide side chain from the protein, was greater, suggesting a lower water activity. The nitroxide side chain also detected a higher viscosity environment in the vicinity of the paramagnetic probe induced by the addition of the surfactants. The results suggest that the surfactant-BSA interaction, at higher surfactant concentration, is affected by the affinities of the surfactant to its own micelles and micelle-like aggregates. Complementary DLS data suggests that the temperature induced changes monitored by the nitroxide probe reflects local changes in the vicinity of the single thiol group of Cys-34 BSA residue. (C) 2011 Elsevier B.V. All rights reserved.

Control of Fusarium in chrysanthemum with sewage sludge, biofertilizer, hydrolyzed fish, chitosan and Trichoderma.

2009