In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction

Studies were performed to investigate the UDP-glucuronosyltransferase enzyme( s) responsible for the human liver microsomal N2-glucuronidation of the anticonvulsant drug lamotrigine ( LTG) and the mechanistic basis for the LTG-valproic acid ( VPA) interaction in vivo. LTG N2-glucuronidation by microsomes from five livers exhibited atypical kinetics, best described by a model comprising the expressions for the Hill ( 1869 +/- 1286 mu M, n = 0.65 +/- 0.16) and Michaelis-Menten ( Km 2234 +/- 774 mu M) equations. The UGT1A4 inhibitor hecogenin abolished the Michaelis-Menten component, without affecting the Hill component. LTG N2-glucuronidation by recombinant UGT1A4 exhibited Michaelis-Menten kinetics, with a K-m of 1558 mu M. Although recombinant UGT2B7 exhibited only low activity toward LTG, inhibition by zidovudine and fluconazole and activation by bovine serum albumin ( BSA) ( 2%) strongly suggested that this enzyme was responsible for the Hill component of microsomal LTG N2-glucuronidation. VPA ( 10 mM) abolished the Hill component of microsomal LTG N2-glucuronidation, without affecting the Michaelis-Menten component or UGT1A4-catalyzed LTG metabolism. K-i values for inhibition of the Hill component of LTG N2-glucuronidation by VPA were 2465 +/- 370 mu M and 387 +/- 12 mu M in the absence and presence, respectively, of BSA ( 2%). Consistent with published data for the effect of fluconazole on zidovudine glucuronidation by human liver microsomal UGT2B7, the Ki value generated in the presence of BSA predicted the magnitude of the LTG-VPA interaction reported in vivo. These data indicate that UGT2B7 and UGT1A4 are responsible for the Hill and Michaelis-Menten components, respectively, of microsomal LTG N2-glucuronidation, and the LTG-VPA interaction in vivo arises from inhibition of UGT2B7.

Beach face and berm morphodynamics fronting a coastal lagoon

This study documents two different modes of berm development: (I) vertical growth at spring tides or following significant beach cut due to substantial swash overtopping, and (2) horizontal progradation at neap tides through the formation of a proto-berm located lower and further seaward of the principal berm. Concurrent high-frequency measurements of bed elevation and the associated wave runup distribution reveal the details of each of these berm growth modes. In mode I sediment is eroded from the inner surf and lower swash zone where swash interactions are prevalent. The net transport of this sediment is landward only, resulting in accretion onto the upper beach face and over the berm crest. The final outcome is a steepening of the beach face gradient, a change in the profile shape towards concave and rapid vertical and horizontal growth of the berm. In mode 2 sediment is eroded from the lower two-thirds of the active swash zone during the rising tide and is transported both landward and seaward. On the falling tide sediment is eroded from the inner surf and transported landward to backfill the zone eroded on the rising tide. The net result is relatively slow steepening of the beach face, a change of the profile shape towards convex, and horizontal progradation through the formation of a neap berm. The primary factor determining which mode of berm growth occurs is the presence or absence of swash overtopping at the time of sediment accumulation on the beach face. This depends on the current phase of the spring-neap tide cycle, the wave runup height (and indirectly offshore wave conditions) and the height of the pre-existing berm. A conceptual model for berm morphodynamics is presented, based on sediment transport shape functions measured during the two modes of berm growth. (c) 2006 Elsevier B.V. All rights reserved.

Parthenium weed: a potential major weed for agro-ecosystems in Pakistan

Parthenium weed (Parthenium hysterophorus L.) is a new and potentially major weed in Pakistan. This weed, originating from central America, is now a major weed in many regions of the world including Eastern Africa, India, parts of South East Asia and Australia. Presumably its recent arrival in Pakistan has been due to its movement from India, but this has yet to be established. In Australia it has been present for about 50 years, in which time it has spread from isolated infestations to establish core populations in central Queensland with scattered and isolated plants occurring south into New South Wales and north-west into the Northern Territory. Its spread in Pakistan is likely to be much more rapid, but lessons learnt in Australia will be of great value for weed managers in Pakistan. This annual herb has the potential to spread to all medium rainfall rangeland, dairy and summer cropping areas in Pakistan. In Australia its main effect is upon livestock production, but it is also causing health concerns in regional communities. However, in India it has also had a significant impact in cropping systems. To help coordinate actions on its management in Australia, a National Weeds Program has created a Parthenium Weed Management Group (PWMG) and under this group a Parthenium Weed Research Group (PWRG) has been formed. Funding coming from this national program and other sources has supported the PWRG to undertake a collaborative and technology exchange research program in two main areas: 1) biology and ecology and 2) management; while the PWMG has focused on community awareness and the production of various extension and management packages. Research in the area of biology and ecology has included studies on the evaluation of competitive plants to displace parthenium weed, the use of process-based simulation models to monitor and predict future spread and abundance under present and future climate conditions, the effect of the weed on human health and the ecology of its seed bank. Management research has focussed on the development of biological control approaches using plant-feeding insects and pathogens. The effectiveness of biological control is also being monitored through long term studies on seed bank size and dynamics. The use of fire as another potential management tool is also being evaluated. In addition to this important research, an effort has also been made to spread the most important findings and management outcomes to the wider community through an extension and education program driven by the PWMG. These developments within Australia, in parthenium weed management, will be of great help to P

Career development: A project for the 21st century

This article reports of the papers present at the International Symposium 2006 'Shaping the future: connecting career development and workforce development'. The International Symposium 2006 provided an opportunity to move the project forward by considering career development in relation to the workforce development issues of human capital, labour supply, employability skills and older workers. In addition to these specific issues, it examined the broader issues of how career development services might contribute to workforce development and the career development information base needed to support public policy making. By way of background to this special issue on the International Symposium 2006, this paper briefly examines the context and the reasons behind career development's rise to a more prominent position on the public policy arena. Following this, the process of the International Symposium 2006 that resulted in the writing of the documents contained in the special issue are briefly outlined.

International symposium on career development and public policy: Synthesis of country papers

During the conference, country teams were asked to select and address selection of six themes: human capital, labour supply, employability skills, carer development services for workforce development, older workers or evidence based research. This synthesis of country papers covers the conceptual links between these themes. It then goes on to cover three reframed themes focusing on career development policies and services, but distinguishing three levels of such policies and services: workforce preparation, workforce adaptability and workforce re-integration.

Dominance hierarchies and health: Constructing personal zones of spiritual power and healing in modern medicine

Ethological studies of animals in groups and sociobiology indicate that hierarchies of dominance amongst some species ensure the survival of the group. When transferred to human groups, dominance hierarchies suggest a crucial role played by recasting the scope of such hierarchies of dominant and subordinate members to included hyper-dominant beings. A recognition of such beings as even more dominant than the socially dominant members of a hierarchy facilitates the empowerment of the socially subordinate members. Religious belief and practice works to establish such hyper-dominant beings (gods, goddesses, and so forth) as superior members of human groups. Doing so is a means of ensuring the survival of the species and, thus, enhancing healing and human health. The doctor-patient relationship is examined from such a point of view, with an emphasis on whether the hierarchy created by the relationship allows consideration of alternative and complementary forms of medical treatment.

Detection of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2(PAI-2) in gingival crevicular fluid from healthy, gingivitis and periodontitis patients

Background: The regulation of plasminogen activation is a key element in controlling proteolytic events in the extracellular matrix. Our previous studies had demonstrated that in inflamed gingival tissues, tissue-type plasminogen activator (t-PA) is significantly increased in the extracellular matrix of the connective tissue and that interleukin 1 beta (IL-1 beta) can up regulate the level of t-PA and plasminogen activator inhibitor-2 (PAI-2) synthesis by human gingival fibroblasts. Method: In the present study, the levels of t-PA and PAI-2 in gingival crevicular fluid (GCF) were measured from healthy, gingivitis and periodontitis sites and compared before and after periodontal treatment. Crevicular fluid from 106 periodontal sites in 33 patients were collected. 24 sites from 11 periodontitis patients received periodontal treatment after the first sample collection and post-treatment samples were collected 14 days after treatment. All samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for t-PA and PAI-2. Results: The results showed that significantly high levels of t-PA and PAI-2 in GCF were found in the gingivitis and periodontitis sites. Periodontal treatment led to significant decreases of PAI-2, but not t-PA, after 14 days. A significant positive linear correlation was found between t-PA and PAI-2 in GCF (r=0.80, p

The handbook of physical education

What is the current condition of the field of physical education? How has it adapted to the rise of kinesiology, sport and exercise science and human movement studies over the last thirty years? This Handbook provides an authoritative critical overview of the field and identifies future challenges and directions. The Handbook is divided in to six parts: - Perspectives and Paradigms in Physical Education Pedagogy Research; - Cross-disciplinary Contributions to Research on Physical Education; - Learners and Learning in Physical Education; - Teachers, Teaching and Teacher Education in Physical Education; - Physical Education Curriculum; - Difference and Diversity in Physical Education. This benchmark work is essential reading for educators and students in the field of physical education.