Understanding environmental influences on walking - Review and research agenda

Background: Understanding how environmental attributes can influence particular physical activity behaviors is a public health research priority. Walking is the most common physical activity behavior of adults; environmental innovations may be able to influence rates of participation. Method: Review of studies on relationships of objectively assessed and perceived environmental attributes with walking. Associations with environmental attributes were examined separately for exercise and recreational walking, walking to get to and from places, and total walking. Results: Eighteen Studies were identified. Aesthetic attributes, convenience of facilities for walking (sidewalks, trails); accessibility of destinations (stores, park, beach); and perceptions about traffic and busy roads were found to be associated with walking for particular purposes. Attributes associated with walking for exercise were different front those associated with walking to get to and from places. Conclusions: While few studies have examined specific environment-walking relationships, early evidence is promising. Key elements of the research agenda are developing reliable and valid measures of environmental attributes and walking behaviors, determining whether environment-behavior relationships are causal, and developing theoretical models that account for environmental influences and their interactions with other determinants. (C) 2004 American Journal of Preventive Medicine.

Effects of physical disturbance on infaunal and epifaunal assemblages in subtropical, intertidal seagrass beds

We assessed the impact of large-scale commercial and recreational harvesting of polychaete worms Marphysa spp. on macrobenthic assemblages in a subtropical estuary in Queensland, Australia, by examining: (1) the spatial extent of harvesting activities and the rate of recovery of the seagrass habitat over an 18 to 20 mo period; (2) the recovery of infauna in and around commercial pits of known age; (3) the indirect effects of physical disturbance from trampling and deposition of sediments during harvesting on epibenthos in areas adjacent to commercial and recreational pits; (4) impacts of potential indirect effects through manipulative experimentation. Harvesting caused a loss of seagrass, changes to the topography and compaction of the sediments associated with the creation of walls around commercial pits, and the deposition of rubble dug from within the pit. The walls and rubble were still evident after 1.8 to 20 mo, but comprised only a small proportion of the total area on the intertidal banks. There was a shift from an intertidal area dominated by Zostera capricorni to one with a mixture of Z. capricorni, Halophila spp. and Halodule uninervis, but there was no overall decline in the biomass of seagrass in these areas. There were distinct impacts from harvesting on the abundance of benthic infauna, especially amphipods, polychaetes and gastropods, and these effects were still detectable after 4 mo of potential recovery. After 12 me, there were no detectable differences in the abundances of these infauna between dug areas and reference areas, which suggested that infauna had recovered from impacts of harvesting; however, an extensive bloom of toxic fireweed Lyngbya majsucula may have masked any remaining impacts. There were no detectable impacts of harvesting on epifauna living in the seagrass immediately around commercial or recreational pits.

Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria

Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for drug development. Recent studies have shown that clinically utilized human immunodeficiency virus (HIV) protease inhibitors can inhibit the in vitro growth of Plasmodium falciparum at or below concentrations found in human plasma after oral drug administration. The most potent in vitro antimalarial effects have been obtained for parasites treated with saquinavir, ritonavir, or lopinavir, findings confirmed in this study for a genetically distinct P. falciparum line (3D7). To investigate the potential in vivo activity of antiretroviral protease inhibitors (ARPIs) against malaria, we examined the effect of ARPI combinations in a murine model of malaria. In mice infected with Plasmodium chabaudi AS and treated orally with ritonavir-saquinavir or ritonavir-lopinavir, a delay in patency and a significant attenuation of parasitemia were observed. Using modeling and ligand docking studies we examined putative ligand binding sites of ARPIs in aspartyl proteases of P. falciparum (plasmepsins II and IV) and P. chabaudi (plasmepsin) and found that these in silico analyses support the antimalarial activity hypothesized to be mediated through inhibition of these enzymes. In addition, in vitro enzyme assays demonstrated that P. falciparum plasmepsins II and IV are both inhibited by the ARPIs saquinavir, ritonavir, and lopinavir. The combined results suggest that ARPIs have useful antimalarial activity that may be especially relevant in geographical regions where HIV and P. falciparum infections are both endemic.

Lead compounds for antimalarial chemotherapy: Purine base analogs discriminate between human and P-falciparum 6-oxopurine phosphoribosyltransferases

The malarial parasite Plasmodium falciparum depends on the purine salvage enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) to convert purine bases from the host to nucleotides needed for DNA and RNA synthesis. An approach to developing antimalarial drugs is to use HGXPRT to convert introduced purine base analogs to nucleotides that are toxic to the parasite. This strategy requires that these compounds be good substrates for the parasite enzyme but poor substrates for the human counterpart, HGPRT. Bases with a chlorine atom in the 6-position or a nitrogen in the 8-position exhibited strong discrimination between P. falciparum HGXPRT and human HGPRT. The k(cat)/K-m values for the Plasmodium enzyme using 6-chloroguanine and 8-azaguanine as substrates were 50-80-fold and 336-fold higher than for the human enzyme, respectively. These and other bases were effective in inhibiting the growth of the parasite in vitro, giving IC50 values as low as 1 mu M.

Origin and possible roles of the Sox8 transcription factor gene during sexual development

Sox8 is a member of the Sox family of developmental transcription factor genes and is closely related to Sox9, a critical gene involved in mammalian sex determination and differentiation. Both genes encode proteins with the ability to bind similar DNA target sequences, and to activate transcription in in vitro assays. Expression studies indicate that the two genes have largely overlapping patterns of activity during mammalian embryonic development. A knockout of Sox8 in mice has no obvious developmental phenotype, suggesting that the two genes are able to act redundantly in a variety of developmental contexts. In particular, both genes are expressed in the developing Sertoli cell lineage of the developing testes in mice, and both proteins are able to activate transcription of the gene encoding anti-Mullerian hormone (AMH), through synergistic action with steroidogenic factor I (SF1). We have hypothesized that Sox8 may substitute for Sox9 in species where Sox9 is expressed too late to be involved in sex determination or regulation of Amh expression. However, our studies involving the red-eared slider turtle indicate that Sox8 is expressed at similar levels in males and females throughout the sex-determining period, suggesting that Sox8 is neither a transcriptional regulator for Amh, nor responsible for sex determination or gonad differentiation in that species. Similarly, Sox8 is not expressed in a sexually dimorphic pattern during gonadogenesis in the chicken. Since a functional role(s) for Sox8 is implied by its conservation during evolution, the significance of Sox8 for sexual and other aspects of development will need to be uncovered through more directed lines of experimentation. Copyright (C) 2003 S. Karger AG, Basel.

D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A(2) (IIa) with antiinflammatory activity

Few reported inhibitors of secretory phospholipase A(2) enzymes inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at submicromolar concentrations. Herein, the simple chiral precursor D-tyrosine was derivastised to give a series of potent new inhibitors of hnpsPLA(2)-IIa. A 2.2-Angstrom crystal structure shows an inhibitor bound in the active site of the enzyme, chelated to a Ca2+ ion through carboxylate and amide oxygen atoms, H bonded through an amide NH group to His48, with multiple hydrophobic contacts and a T-shaped aromatic-group-His6 interaction. Antiinflammatory activity is also demonstrated for two compounds administered orally to rats.

Physical activity as a dimension of family life for lower primary school children

While questions of children's engagement in physical activity are being widely debated, little is known about how physical activity is valued and managed within families. This paper reports on qualitative data from a multi-method study on lower primary aged children. The focus of the broader study was to determine the relationships between young children's physical activity patterns, skills, and recreational interests, and their families' location, income, commitment to physical activity, and other responsibilities. Drawing on interviews with 12 purposively selected families, it was found that physical activity was highly valued across different family contexts, that children's engagement was shaped by their interests, friendships, and safety, and that issues such as income, family configuration, parental work commitments, and transport were potential barriers to further engagement.

Drugs to treat inflammation: A historical introduction

Drugs to treat inflammation are discussed under the following headings: (1) random discoveries covering copper, salicylates, heterocyclic diones, ACTH, adrenal steroids and disease-modifying agents (DMARDs); these include Au(I)-thiolates, chloroquine, and hydroxychloroquine, minocycline, cyclosporin, salazopyrine, D-penicillamine and methotrexate; (2) programmed NSAID developments covering salicylates and fenamates, arylalkanoates, diones, non-acidic NSAIDs, clozic, lobenzarit and coxibs; (3) synthetic glucocorticosteroids; and (4) 'Biologicals' for neutralising pro-inflammatory cytokines. Clinical problems are highlighted, particularly unacceptable side-effects affecting the GI tract, skin, liver, etc. that caused many drugs to be withdrawn. Drug combinations may overcome some of these problems. The bibliography has selected reviews and monographs covering 50 years of publications.