Control of ion transport in mammalian airways by protease activated receptors type 2 (PAR-2)

Protease-activated receptors (PARs) are widely distributed in human airways. They couple to G-proteins and are activated after proteolytic cleavage of the N terminus of the receptor. Evidence is growing that PAR subtype 2 plays a pivotal role in inflammatory airway diseases, such as allergic asthma or bronchitis. However, nothing is known about the effects of PAR-2 on electrolyte transport in the native airways. PAR-2 is expressed in airway epithelial cells, where they are activated by mast cell tryptase, neutrophil proteinase 3, or trypsin. Recent studies produced conflicting results about the functional consequence of PAR-2 stimulation. Here we report that stimulation of PAR-2 receptors in mouse and human airways leads to a change in electrolyte transport and a shift from absorption to secretion. Although PAR-2 appears to be expressed on both sides of the epithelium, only basolateral stimulation results in inhibition of amiloride sensitive Na+ conductance and stimulation of both luminal Cl- channels and basolateral K+ channels. The present data indicate that these changes occur through activation of phospholipase C and increase in intracellular Ca2+, which activates basolateral SK4 K+ channels and luminal Ca2+-dependent Cl- channels. In addition, the present data suggest a PAR-2 mediated release of prostaglandin E2, which may contribute to the secretory response. In conclusion, these results provide further evidence for a role of PAR-2 in inflammatory airway disease: stimulation of these receptors may cause accumulation of airway surface liquid, which, however, may help to flush noxious stimuli away from the affected airways. ©2005 FASEB

Spatial and ontogenetic variation in growth of nursery-bound juvenile lemon sharks, Negaprion brevirostris: a comparison of two age-assigning techniques

We compared growth rates of the lemon shark, Negaprion brevirostris, from Bimini, Bahamas and the Marquesas Keys (MK), Florida using data obtained in a multi-year annual census. We marked new neonate and juvenile sharks with unique electronic identity tags in Bimini and in the MK we tagged neonate and juvenile sharks. Sharks were tagged with tiny, subcutaneous transponders, a type of tagging thought to cause little, if any disruption to normal growth patterns when compared to conventional external tagging. Within the first 2 years of this project, no age data were recorded for sharks caught for the first time in Bimini. Therefore, we applied and tested two methods of age analysis: ( 1) a modified 'minimum convex polygon' method and ( 2) a new age-assigning method, the 'cut-off technique'. The cut-off technique proved to be the more suitable one, enabling us to identify the age of 134 of the 642 previously unknown aged sharks. This maximised the usable growth data included in our analysis. Annual absolute growth rates of juvenile, nursery-bound lemon sharks were almost constant for the two Bimini nurseries and can be best described by a simple linear model ( growth data was only available for age-0 sharks in the MK). Annual absolute growth for age-0 sharks was much greater in the MK than in either the North Sound (NS) and Shark Land (SL) at Bimini. Growth of SL sharks was significantly faster during the first 2 years of life than of the sharks in the NS population. However, in MK, only growth in the first year was considered to be reliably estimated due to low recapture rates. Analyses indicated no significant differences in growth rates between males and females for any area.

Plant-based immunocontraceptive control of wildlife - "potentials, limitations, and possums"

Possums (Trichosurus vulpecula), originally introduced from Australia, are spread over 90% of New Zealand and cause major economic and environmental damage. Immunocontraception has been suggested as a humane means to control them. Marsupial-specific reproductive antigens expressed at high levels in edible transgenic plant tissue might provide a safe, effective, and cheap oral delivery bait for immuno-contraceptive control. As proof of concept, female possums vaccinated with immunocontraceptive antigens showed reduced fertility, and possums fed with potato-expressed heat labile toxin-B (LT-B) had mucosal and systemic immune responses to the antigen. This demonstrated that immunocontraception was effective in possums and that oral delivery in edible plant material might be possible. Nuclear transformation with reporter genes showed that transgenic carrot roots accumulate high levels of foreign protein in edible tissues, indicating their potential as a delivery vector. However, prior to attempts at large scale production, more effective immunocontraceptive antigen-adjuvant formulations are probably required before plant-based immunocontraception can become a major tool for immunocontraceptive control of overabundant vertebrate pests. (c) 2004 Elsevier Ltd. All rights reserved.

Role of smoking in global and regional cardiovascular mortality

Background - Smoking is a major cause of cardiovascular disease mortality. There is little information on how it contributes to global and regional cause-specific mortality from cardiovascular diseases for which background risk varies because of other risks. Method and Results - We used data from the American Cancer Society's Cancer Prevention Study II (CPS II) and the World Health Organization Global Burden of Disease mortality database to estimate smoking-attributable deaths from ischemic heart disease, cerebrovascular disease, and a cluster of other cardiovascular diseases for 14 epidemiological subregions of the world by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.62 (95% CI, 1.27 to 2.04) million cardiovascular deaths in the world, 11% of total global cardiovascular deaths, were due to smoking. Of these, 1.17 million deaths were among men and 450 000 among women. There were 670 000 (95% CI, 440 000 to 920 000) smoking-attributable cardiovascular deaths in the developing world and 960 000 (95% CI, 770 000 to 1 200 000) in industrialized regions. Ischemic heart disease accounted for 54% of smoking-attributable cardiovascular mortality, followed by cerebrovascular disease (25%). There was variability across regions in the role of smoking as a cause of various cardiovascular diseases. Conclusions - More than 1 in every 10 cardiovascular deaths in the world in the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality.

Diabetes as a tracer condition in international benchmarking of health systems

OBJECTIVE - To assess the performance of health systems using diabetes as a tracer condition. RESEARCH DESIGN AND METHODS - We generated a measure of case-fatality among young people with diabetes Using the mortalily-to-incidence ratio (M/I ratio) for 29 industrialized countries using published data on diabetes incidence and mortality. Standardized incidence rates for ages 0-14 years were extracted from the World Health Organization DiaMond Study for the period 1990-1994; data on death from diabetes for ages 0-39 years were obtained from the World Health Organization Mortality database and converted into age-standardized death rates for the period 1994-1998, using the European standard population. RESULTS - The MA ratio varied > 10-fold. These relative differences appear similar to those observed in cohort studies of mortality among young people with type I diabetes in five countries. A sensitivity analysis showed that using plausible assumptions about potential overestimation of diabetes as a cause of death and underestimation of incidence rates in the U.S. yields an M/I ratio that would still be twice as high as in the U.K. or Canada. CONCLUSIONS - The M/I ratio for diabetes provides a means of differentiating countries on quality of care for people with diabetes. It is solely an indicator of potential problems, a basis for Stimulating more detailed assessments of whether such problems exist, and what can be done to address them.

Field evaluation of passive samplers: Monitoring polycyclic aromatic hydrocarbons (PAHs) in stormwater

The aim of this study was to evaluate the feasibility of using semipermeable membrane devices (SPMDs) and polyethylene-based passive sampler devices (PSDs) for monitoring PAHs in stormwater. Firstly, SPMDs were deployed at one site and SPMD-derived water concentrations were compared with water concentration measured from grab samples. In a subsequent deployment the performance of SPMDs and PSDs was compared. Finally PSDs of multiple surface area to volume ratios were used to compare PAH concentrations at the two sites. The results obtained in this study show that SPMDs can be used to measure the water concentration of PAHs with reasonable accuracy, when compared with grab samples collected at the same site. Importantly, several PAHs which could not be detected in a 10 L grab sample could be detected in the SPMDs. PSD and SPMD samplers produced similar results when deployed at the same site, with most estimated water concentrations within a factor of 1.5. The use of PSDs in multiple surface area to volume ratios proved to be an effective means of characterizing the uptake kinetics for PAHs in situ. Overall passive water samplers proved to be an efficient technique for monitoring PAHs in stormwater.

The phonological awareness abilities of children with cerebral palsy who do not speak

To investigate the importance of the connection between being able to speak and the emergence of phonological awareness abilities, the performance of children with cerebral palsy (five speakers and six non-speakers) was assessed at syllable, onset-rime, and phoneme levels. The children were matched with control groups of children for non-verbal intelligence. No group differences were found for the identification of syllables, reading non-words, or judging spoken rhyme. The children with cerebral palsy who could speak, however, performed better than the children with cerebral palsy who could not speak and the control group of children without disabilities, judging written words for rhyme. The children with cerebral palsy who could not speak performed poorly in comparison to those who could speak ( but not the control group of children) when segmenting syllables and on the phoneme manipulation task. The findings suggest that non-speaking children with cerebral palsy have phonological awareness performance that varies according to the mental processing demands of the task. The ability to speak facilitates performance when phonological awareness tasks ( written rhyme judgment, syllable segmentation, and phoneme manipulation) require the use of an articulatory loop.