NORMAL COORDINATE TREATMENT OF LEU(5)-ENKEPHALIN IN THE CRYSTAL-STATE

Vibrational studies on the neuropentapeptide Leu5-enkephalin were performed for the crystal state where different specific conformations can arise. In the present case, the peptide adopts a double fused folded conformation (beta-turn), the presence of which in the crystal state is directly related to the nature of the solvent used for its crystallization. This study completes other work relating to similar conformations of isolated molecules. It can be seen that specific interactions in the crystal state perturb to a large extent the vibrational relationships between the amide frequencies and the specific sets of dihedral angles characteristic of the particular type of turn. The tyrosyl moiety and its frequency dependence on its hydrogen bond state was especially investigated both for the Fermi resonance and the hydroxyl bending modes.

AN EXPERIMENTAL-STUDY ON MEMBRANE DISTILLATION FOR TREATMENT OF GINSENG DEW AND GINSENG WASHING WATER

Membrane distillation is a new membrane separation process which has been developed in the last few years. When a piece of microporous hydrophobic membrane separates two kinds of aqueous solutions different in temperature, the solutions cannot transport through the pores of membrane in any directions because of the hydrophobicity of membrane. However, vapor can readily penetrate through the

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximate to 20,000 microbial extracts, 12 hits were identified with broadspectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.

Alkaline treatment of the cellulose fiber affecting membrane column behaviour for high-performance immunoaffinity chromatography

The original cellulose fibers and those treated by alkaline solution were both used to prepare the acrylic membranes. The two kinds of membranes were packed into the columns for high-performance immunoaffinity chromatography by the immobilization of protein A on them. It was observed that the alkaline treatment of the cellulose fiber decreased the pressure resistance of the membrane to the mobile phases and greatly increased the accessible volume to the proteins, but affected the adsorption capacity of human IgG on the protein A membrane columns less. There is little difference between those two kinds of membranes on the adsorption capacities of HIgG, which means that the alkaline treatment of the cellulose fiber only significantly changes the void volume inter-membrane, and the porosity and surface area of membrane less. Alkaline treatment of the cellulose fiber reduced the membrane-column efficiency significantly. Some typical examples for the immunoaffinity analysis of IgG from human and dog plasma on the protein A membrane columns are illustrated. Copyright (C) 2000 John Wiley & Sons, Ltd.

Enhancement of boron removal in treatment of spent rinse from a plating operation using RO

Boron removal is a critical issue in the production of drinking water and of ultra-pure water in the electronics industry. Boron rejection in a RO process is typically in the range of 40-60%. The objective of this study was to distinguish the factor contributing to enhanced boron rejection in reclamation of a spent rinse stream from a plating operation. The effects of different known components used in the feed on boron removal were investigated in the laboratory. The results indicated that glycolic acid and antifoulants could not individually enhance boron rejection in a RO process. A high boron rejection of 95% was achieved as the concentration of iron in the feed was 10 times higher than that of boron, which might be due to formation of a complex between iron oxide and boron. The finding was confirmed in a pilot study.

Mandibular Manipulation for the Treatment of Temporomandibular Disorder

The aim of this study was to conduct a systematic review to identify the randomized clinical studies that had investigated the following research question: Is the mandibular manipulation technique an effective and safe technique for the treatment of the temporomandibular joint disk displacement without reduction? the systematic search was conducted in the electronic databases: PubMed (Medical Publications), LILACS (Latin American and Caribbean Literature in Health Sciences), EMBASE (Excerpta Medica Database), PEDro (Physiotherapy Evidence Database), BBO (Brazilian Library of Odontology), CENTRAL (Library Cochrane), and SciELO (Scientific Electronic Library Online). the abstracts of presentations in physical therapy meetings were manually selected, and the articles of the ones that meet the requirements were investigated. No language restrictions were considered. Only randomized and controlled clinical studies were included. Two studies of medium quality fulfilled all the inclusion criteria. There is no sufficient evidence to support the effectiveness of the mandibular manipulation therapy, and therefore its use remains questionable. Being minimally invasive, this therapy is attractive as an initial approach, especially considering the cost of the alternative approaches. the analysis of the results suggests that additional high-quality randomized clinical trials are necessary on the topic, and they should focus on methods for data randomization and allocation, on clearly defined outcomes, on a priori calculated sample size, and on an adequate follow-up strategy.

Biological rationale for regular physical exercise as an effective intervention for the prevention and treatment of depressive disorders

Depression is a major medical and social problem. Here we review current body of knowledge on the benefits of exercise as an effective strategy for both the prevention and treatment of this condition. We also analyze the biological pathways involved in such potential benefits, which include changes in neurotrophic factors, oxidative stress and inflammation, telomere length, brain volume and microvessels, neurotransmitters or hormones. We also identify major caveats in this field of research: further studies are needed to identify which are the most appropriate types of exercise interventions (intensity, duration, or frequency) to treat and prevent depression.

Treatment of HIV/AIDS at South Africa's Largest Employers: Myth and Reality

Background: In the past three years, many large employers in South Africa have announced publicly their intention of making antiretroviral treatment (ART) available to employees. Reports of the scope and success of these programs have been mostly anecdotal. This study surveyed the largest private sector employers in South Africa to determine the proportion of employees with access to ART through employer-sponsored HIV/AIDS treatment programs. Methods: All 64 private sector and parastatal employers in South Africa with more than 6,000 employees were identified and contacted. Those that agreed to participate were interviewed by telephone using a structured questionnaire. Results: 52 companies agreed to participate. Among these companies, 63% of employees had access to employer-sponsored care and treatment for HIV/AIDS. Access varied widely by sector, however. Approximately 27% of suspected HIV-positive employees were enrolled in HIV/AIDS disease management programs, or 4.4% of the workforce overall. Fewer than 4,000 employees in the entire sample were receiving antiretroviral therapy. In-house (employer) disease management programs and independent disease management programs achieved higher uptake of services than did medical aid schemes. Conclusions: Publicity by large employers about their treatment programs should be interpreted cautiously. While there is a high level of access to treatment, uptake of services is low and only a small fraction of employees medically eligible for antiretroviral therapy are receiving it.

Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth offers a considerable degree of protection from a wide variety of challenges such as the host immune system or antibiotic therapy. The threat posed by the emergence of chronic pathogens is prompting the development of next generation antimicrobials. The biofilm mode of growth is often central to the establishment of chronic infection and the development of antibiotic resistance. Thus, targeting biofilm formation has emerged as one of the principle strategies for the development of next generation antimicrobials. In this thesis two separate approaches were used to identify potential anti - biofilm targets. The first strategy focused on the identification of novel genes with a role in a biofilm formation. High throughput screening identified almost 300 genes which had a role in biofilm formation. A number of these genes were characterised at a phenotypic and a molecular level. The second strategy focused on the identification of compounds capable of inhibiting biofilm formation. A collection of marine sponge isolated bacteria were screened for the ability to inhibit the central pathway regulating biofilm formation, quorum sensing. A number of distinct isolates were identified that had quorum sensing inhibition activity from which, a Pseudomonas isolate was selected for further characterisation. A specific compound capable of inhibiting quorum sensing was identified using chemical analytical technologies in the supernatant of this marine isolate.

The treatment of landfill leachate using natural systems

Leachate may be defined as any liquid percolating through deposited waste and emitted from or contained within a landfill. If leachate migrates from a site it may pose a severe threat to the surrounding environment. Increasingly stringent environmental legislation both at European level and national level (Republic of Ireland) regarding the operation of landfill sites, control of associated emissions, as well as requirements for restoration and aftercare management (up to 30 years) has prompted research for this project into the design and development of a low cost, low maintenance, low technology trial system to treat landfill leachate at Kinsale Road Landfill Site, located on the outskirts of Cork city. A trial leachate treatment plant was constructed consisting of 14 separate treatment units (10 open top cylindrical cells [Ø 1.8 m x 2.0 high] and four reed beds [5.0m x 5.0m x 1.0m]) incorporating various alternative natural treatment processes including reed beds (vertical flow [VF] and horizontal flow [HF]), grass treatment planes, compost units, timber chip units, compost-timber chip units, stratified sand filters and willow treatment plots. High treatment efficiencies were achieved in units operating in sequence containing compost and timber chip media, vertical flow reed beds and grass treatment planes. Pollutant load removal rates of 99% for NH4, 84% for BOD5, 46% for COD, 63% for suspended solids, 94% for iron and 98% for manganese were recorded in the final effluent of successfully operated sequences at irrigation rates of 945 l/m2/day in the cylindrical cells and 96 l/m2/day in the VF reed beds and grass treatment planes. Almost total pathogen removal (E. coli) occurred in the final effluent of the same sequence. Denitrification rates of 37% were achieved for a limited period. A draft, up-scaled leachate treatment plant is presented, based on treatment performance of the trial plant.

Towards the enantioselective synthesis of Plakortide P and its application to the development of drugs for the treatment of Chagas disease

The primary focus of this thesis was the asymmetric peroxidation of α,β-unsaturated aldehydes and the development of this methodology to include the synthesis of bioactive chiral 1,2-dioxane and 1,2-dioxalane rings. In Chapter 1 a review detailing the new and improved methods for the acyclic introduction of peroxide functionality to substrates over the last decade was discussed. These include a detailed examination of metal-mediated transformations, chiral peroxidation using organocatalytic means and the improvements in methodology of well-established peroxidation pathways. The second chapter discusses the method by which peroxidation of our various substrates was attempted and the optimisation studies associated with these reactions. The method by which the enantioselectivity of our β-peroxyaldehydes was determined is also reviewed. Chapters 3 and 4 focus on improving the enantioselectivity associated with our asymmetric peroxidation reaction. A comprehensive analysis exploring the effect of solvent, concentration and temperature on enantioselectivity was examined. The effect that different catalytic systems have on enantioselectivity and reactivity was also investigated in depth. Chapter 5 details the various transformations that β-peroxyaldehydes can undergo and the manipulation of these transformations towards the establishment of several routes for the formation of chiral 1,2-dioxane and 1,2-dioxalane rings. Chapter 6 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.

Mesenchymal stem cell therapy for the treatment of myocardial infarction

Mesenchymal stem cells (MSCs) are currently under investigation as repair agents in the preservation of cardiac function following myocardial infarction (MI). However concerns have emerged regarding the safety of acute intracoronary (IC) MSC delivery specifically related to mortality, micro-infarction and microvascular flow restriction post cell therapy in animal models. This thesis aimed to firstly identify an optimal dose of MSC that could be tolerated when delivered via the coronary artery in a porcine model of acute MI (AMI). Initial dosing studies identified 25x106 MSC to be a safe MSC cell dose, however, angiographic observations from these studies recognised that on delivery of MSC there was a significant adverse decrease in distal blood flow within the artery. This observation along with additional supportive data in the literature (published during the course of this thesis) suggested MSC may be contributing to such adverse events through the propagation of thrombosis. Therefore further studies aimed to investigate the innate prothrombotic activity of MSC. Expression of the initiator of the coagulation cascade initiator tissue factor (TF) on MSC was detected in high levels on the surface of these cells. MSC-derived TF antigen was catalytically active, capable of supporting thrombin generation in vitro and enhancing platelet-driven thrombus deposition on collagen under flow. Infusion of MSC via IC route was associated with a decreased coronary flow reserve when delivered but not when coadministered with an antithrombin agent heparin. Heparin also reduced MSC-associated in situ thrombosis incorporating platelets and VWF in the microvasculature. Heparin-assisted MSC delivery reduced acute apoptosis and significantly improved infarct size, left ventricular ejection fraction, LV volumes, wall motion and scar formation at 6 weeks post AMI. In addition, this thesis investigated the paracrine factors secreted by MSC, in particular focusing on the effect on cardiac repair of a novel MSC-paracrine factor SPARCL1. In summary this work provides new insight into the mechanism by which MSC may be deleterious when delivered by an IC route and a means of abrogating this effect. Moreover we present new data on the MSC secretome with elucidation of the challenges encountered using a single paracrine factor cardiac repair strategy.