Syntheses of polycationic dendrimers on lipophilic peptide core for complexation and transport of oligonucleotides

Synthesis of novel polycationic lipophilic peptide core(s) was accomplished and these agents successfully transfected human retinal pigment epithelium cells with ODN1 upon complexation with the oligonucleotide. The level of transfection was indirectly measured by the decreased production of the protein hVEGF (human vascular endothelial growth factor) in comparison to the transfection agent cytofectin GSV(TM). (C) 2002 Elsevier Science Ltd. All rights reserved.

Experimental investigation of contaminant transport in coastal groundwater

Contaminant transport in coastal aquifers is of increasing interest since, with the development of coastal areas, contaminants from surface sources may enter coastal aquifers and pollute the groundwater flow. Coastal groundwater flow is complicated because of the presence of a freshwater-saltwater diffusion zone and the tidal variation of sea level at the seaward end. This paper investigates experimentally the behaviour of contaminant plumes with different densities in an unconfined coastal aquifer. Experiments were performed in a flow tank filled with glass beads as the porous medium. Results show that the dense contaminant has a more diffusive front than the less dense one in the seaward direction towards the coastline. The plume becomes more diffusive when it travels closer to the saltwater interface. On the contrary, the less dense contaminant presents a relatively sharp outline. It tends to migrate in the upper portion of the aquifer and exits in a concentrated manner over a small discharge area at the coastline, not further seaward under the sea. Non-dimensional parameters show that instabilities occur in our experiments for a density difference of 1.2% or larger between the contaminant and the ambient water. The experimental results provide guidance for field monitoring and numerical modelling. (C) 2002 Elsevier Science Ltd. All rights reserved.

Attitudes and practices of general practitioners in the diagnosis and management of attention-deficit/hyperactivity disorder

Objective: To assess understanding of, and actual and potential roles in management of attention-deficit/hyperactivity disorder (ADHD) among GPs. Methods: A cross-sectional questionnaire survey of Queensland GPs selected randomly from the Royal Australian College of General Practitioners directory of members was carried out. Main outcome measures were knowledge levels of ADHD, current management practices, referral patterns and self-perceived information and training needs. Results: Three hundred and ninety-nine GPs returned a completed questionnaire (response rate 76%). Roles identified by GPs were: the provisional diagnosis of ADHD and referral to specialist services for confirmation of the diagnosis and initiation of management; assistance with monitoring progress once a management plan was in place; education of the child and their family regarding the disorder; and liaison with the school where necessary. Perceived barriers to increased involvement of GPs were: time and resource constraints of general practice; concerns regarding abuse and addiction liability of prescription stimulants; complex diagnostic issues associated with childhood behavioural problems; and lack of training and education regarding ADHD. Conclusions: General practitioners identify a role for themselves in ADHD care that is largely supportive in nature and involves close liaison with specialist services.

Numerical modelling of contaminant transport in coastal aquifers

This paper employs a two-dimensional variable density flow and transport model to investigate the transport of a dense contaminant plume in an unconfined coastal aquifer. Experimental results are also presented to show the contaminant plume in a freshwater-seawater flow system. Both the numerical and experimental results suggest that the neglect of the seawater interface does not noticeably affect the horizontal migration rate of the plume before it reaches the interface. However, the contaminant will travel further seaward and part of the solute mass will exit under the sea if the higher seawater density is not included. If the seawater density is included, the contaminant will travel upwards towards the beach along the freshwater-saltwater interface as shown experimentally. Neglect of seawater density, therefore, will result in an underestimate of solute mass rate exiting around the coastline. (C) 2002 IMACS. Published by Elsevier Science B.V. All rights reserved.

Transport safety for older people: A study of their experiences, perceptions and management needs

With evidence of increasing accident risk due to age-related declines in health and cognition affecting driver performance, there is a need for research promoting safe mobility of older people. The present study aimed to identify transport options and licensing issues for a group of older people in an Australian community. Ninety-five participants aged 75 and over were interviewed about their driving status and accident record and tested for cognitive ability. After stratification on cognitive level and driver status (current, ex-driver or non-driver), 30 were selected for further in-depth interviews concerning demographics, licence status and impact of change, travel options available and used, and travel characteristics. Considerable reliance on the motor vehicle as the mode of transport and the decision to cease driving were major quality-of-life issues. There was little evidence of planning and support in making the decision to stop driving. Some differences in transport decisions on the basis of cognitive level were evident; however, people with severely compromised cognitive ability (and, therefore, unable to give informed consent) had been excluded. The study suggested the need for resources to assist older people/carers/health professionals to plan for the transition from driver to non-driver and to manage alternative transport options more effectively

Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.

Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20degreesC. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection.

Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ

Neuronal and glial high-affinity transporters regulate extracellular glutamate concentration, thereby terminating synaptic transmission and preventing neuronal excitotoxicity. Glutamate transporter activity has been shown to be modulated by protein kinase C (PKC) in cell culture. This is the first study to demonstrate such modulation in situ, by following the fate of the non-metabolisable glutamate transporter substrate, D-aspartate. In the rat retina, pan-isoform PKC inhibition with chelerythrine suppressed glutamate uptake by GLAST (glutamate/aspartate transporter), the dominant excitatory amino acid transporter localized to the glial Muller cells. This effect was mimicked by rottlerin but not by Go6976, suggesting the involvement of the PKCdelta isoform, but not PKCalpha, beta or gamma. Western blotting and immunohistochemical labeling revealed that the suppression of glutamate transport was not due to a change in transporter expression. Inhibition of PKCdelta selectively suppressed GLAST but not neuronal glutamate transporter activity. These data suggest that the targeting of specific glutamate transporters with isoform-specific modulators of PKC activity may have significant implications for the understanding of neurodegenerative conditions arising from compromised glutamate homeostasis, e.g. glaucoma and amyotrophic lateral sclerosis.

Electrolyte transport in the mouse trachea: No evidence for a contribution of luminal K+ conductance

Recent studies on frog skin acini have challenged the question whether Cl- secretion or Na+ absorption in the airways is driven by luminal K+ channels in series to a basolateral K+ conductance. We examined the possible role of luminal K+ channels in electrolyte transport in mouse trachea in Ussing-chamber experiments. Tracheas of both normal and CFTR (-/-) mice showed a dominant amiloride-sensitive Na+ absorption under both, control conditions and after cAMP-dependent stimulation. The lumen-negative transepithelial voltage was enhanced after application of IBMX and forskolin and Cl- secretion was activated. Electrolyte secretion induced by IBMX and forskolin was inhibited by luminal glibenclamide and the blocker of basolateral Na(+)2Cl(-)K(+) cotransporter azosemide. Similarly, the compound 29313, a blocker of basolateral KCNQ1/KCNE3 K+ channels effectively blocked Cl- secretion when applied to either the luminal or basolateral side of the epithelium. RT-PCR analysis suggested expression of additional K+ channels in tracheal epithelial cells such as Slo1 and Kir6.2. However, we did not detect any functional evidence for expression of luminal K+ channels in mouse airways, using luminal 29313, clotrimazole and Ba2+ or different K+ channel toxins such as charybdotoxin, apamin and alpha-dendrotoxin. Thus, the present study demonstrates Cl- secretion in mouse airways, which depends on basolateral Na(+)2Cl(-)K(+) cotransport and luminal CFTR and non-CFTR Cl- channels. Cl- secretion is maintained by the activity of basolateral K+ channels, while no clear evidence was found for the presence of a luminal K+ conductance.

Ion transport induced by proteinase-activated receptors (PAR2) in colon and airways

Protease-activated receptors type 2 (PAR2) are activated by serine proteases like trypsin and mast cell tryptase. The function and physiological significance of PAR2 receptors is poorly understood, but recent studies suggest a role during inflammatory processes in both airways and intestine. PAR2 receptors are also likely to participate in the control of ion transport in these tissues. We demonstrate that stimulation of PAR2 in airways and intestine significantly enhanced ion transport. Trypsin induced CI- secretion in both airways and intestine when added to the basolateral but not to the luminal side of these tissues. In both airways and intestine, stimulation of ion transport was largely dependent on the increase in intracellular Ca2+. Effects of trypsin were largely reduced by basolateral bumetanide and barium and by trypsin inhibitor. Thrombin, an activator of proteinase-activated receptors types 1, 3, and 4 had no effects on equivalent short-circuit current in either airways or intestine. Expression of PAR2 in colon and airways was further confirmed by reverse transcription-polymerase chain reaction. We postulate that these receptors play a significant role in the regulation of electrolyte transport, which might be important during inflammatory diseases of airways and intestine.

Practices and attitudes to derivatives use in Australian commonwealth organisations

Little is known about risk management in the public sector This study reports on a survey of senior officers in Australian Commonwealth companies and statutory authorities concerning their practice and attitudes towards the use of derivative instruments for risk management. Using a variety of tests, the most important issue identified by respondents concerning the use of derivatives is for budgeting purposes. Of note, respondents rank commonly cited reasons advanced in the private sector such as reduced bankruptcy costs and taxation, as being relatively unimportant, which is consistent with arguments advanced in the paper The results also indicate that there are significant differences in the level of importance in some issues regarding derivatives use across public sector organisations, particularly those differentiated by a documented risk management plan. The study also documents for the first time the extent of derivatives use in the Australian public sector.