One of the major causes of interindividual variation of drug effects is genetic variation of drug metabolism. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions. Polymorphisms are generated by mutations in the genes for these enzymes, which cause decreased, increased, or absent enzyme expression or activity by multiple molecular mechanisms. Moreover, the variant alleles exist in the population at relatively high frequency. Genetic polymorphisms have been described for most drug metabolizing enzymes. The molecular mechanisms of three polymorphisms are reviewed here. The acetylation polymorphism concerns the metabolism of a variety of arylamine and hydrazine drugs, as well as carcinogens by the cytosolic N-acetyltransferase NAT2. Seven mutations of the NAT2 gene that occur singly or in combination define numerous alleles associated with decreased function. The debrisoquine-sparteine polymorphism of drug oxidation affects the metabolism of more than 40 drugs. The poor metabolizer phenotype is caused by several “loss of function” alleles of the cytochrome P450 CYP2D6gene. On the other hand, “ultrarapid” metabolizers are caused by duplication or amplification of an active CYP2D6gene. Intermediate metabolizers are often heterozygotes or carry alleles with mutations that decrease enzyme activity only moderately. The mephenytoin polymorphism affects the metabolism of mephenytoin and several other drugs. Two mutant alleles of CYP2C19have so far been identified to cause this polymorphism.

http://www3.uah.es/farmamol/Public/AnnReviews/PDF/Pharma_Toxicol/Drug_metab_polymorph.pdf

Molecular mechanisms of genetic polymorphisms of drug metabolism.

1. The status of small cetaceans in the North Sea and adjacent waters has been of concern for many years. Shipboard and aerial line transect surveys were conducted to provide accurate and precise estimates of abundance as a basis for conservation strategy in European waters. 2. The survey, known as SCANS (Small Cetacean Abundance in the North Sea), was conducted in summer 1994 and designed to generate precise and unbiased abundance estimates. Thus the intensity of survey was high, and data collection and analysis methods allowed for the probability of detection of animals on the transect line being less than unity and, for shipboard surveys, also allowed for animal movement in response to the survey platform. 3. Shipboard transects covered 20 000 km in an area of 890 000 km2. Aerial transects covered 7000 km in an area of 150 000 km2. 4. Three species dominated the data. Harbour porpoise Phocoena phocoena were encountered throughout the survey area except in the Channel and the southern North Sea. Whitebeaked dolphin Lagenorhynchus albirostris and minke whale Balaenoptera acutorostrata were found mainly in the north-western North Sea. 5. Phocoena phocoena abundance for the entire survey area was estimated as 341 366 [coefficient of variation (CV) = 0.14; 95% confidence interval (CI) = 260 000-449 000]. The estimated number of B. acutorostrata was 8445 (CV = 0.24; 95% CI 5000-13 500). The estimate for L. albirostris based on confirmed sightings of this species was 7856 (CV = 0.30; 95% CI = 4000-13 000). When Atlantic whitesided dolphin Lagenorhynchus acutus and Lagenorhynchus spp. sightings were included, this estimate increased to 11 760 (CV = 0.26; 95% CI 5900-18 500). 6. Shortbeaked common dolphin Delphinus delphis were found almost exclusively in the Celtic Sea. Abundance was estimated as 75 450 (CV = 0.67; 95% CI = 23 000-149 000). 7. Current assessments and recommendations by international fora concerning the impact on P. phocoena of bycatch in gillnet fisheries in the North Sea and adjacent waters are based on these estimates.

/pdf/abundance-of-harbour-porpoise-and-other-cetaceans-in-the-23kyaqspxq.pdf

Abundance of harbour porpoise and other cetaceans in the North Sea and adjacent waters

Cetacean-habitat modeling, although still in the early stages of development, represents a potentially powerful tool for predicting cetacean distributions and understanding the ecological processes determining these distributions. Marine ecosystems vary temporally on diel to decadal scales and spatially on scales from several meters to 1000s of kilometers. Many cetacean species are wide- ranging and respond to this variability by changes in distribution patterns. Cetacean-habitat models have already been used to incorporate this variability into management applications, including im- provement of abundance estimates, development of marine protected areas, and understanding cetacean-fisheries interactions. We present a review of the development of cetacean-habitat models, organized according to the primary steps involved in the modeling process. Topics covered include purposes for which cetacean-habitat models are developed, scale issues in marine ecosystems, cetacean and habitat data collection, descriptive and statistical modeling techniques, model selection, and model evaluation. To date, descriptive statistical techniques have been used to explore cetacean-habitat relationships for selected species in specific areas; the numbers of species and geographic areas exam- ined using computationally intensive statistic modeling techniques are considerably less, and the de- velopment of models to test specific hypotheses about the ecological processes determining cetacean distributions has just begun. Future directions in cetacean-habitat modeling span a wide range of possibilities, from development of basic modeling techniques to addressing important ecological questions.

/pdf/techniques-for-cetacean-habitat-modeling-5d5go6zomh.pdf

Techniques for cetacean-habitat modeling

Consistent evaluation and new recommendations for action are required of protective measures to address threats that were unrecognised or non-existent until recently. Global warming, noise pollution and reduced availability of prey are now of great concern. The all too familiar threats of accidental killing in fishing gear and exposure to toxic chemicals remain almost intractable. This Action Plan reviews threats and offers possible solutions. It also contains a thorough review of the status of species and a list of 57 recommended research projects and education initiatives

/pdf/dolphins-whales-and-porpoises-2002-2010-conservation-action-4eu3kcsdgo.pdf

Dolphins, whales and porpoises : 2002-2010 conservation action plan for the world's cetaceans

We introduce CrossY, a simple drawing application developed as a benchmark to demonstrate the feasibility of goal-crossing as the basis for a graphical user interface. While crossing was previously identified as a potential substitute for the classic point-and-click interaction, this work is the first to report on the practical aspects of implementing an interface solely based on goal-crossing.

CrossY: a crossing-based drawing application

Arylamine N-acetyltransferase in human red blood cells.

Samples of sperm whale skin, useful for modern molecular analyses of DNA, can be obtained from living animals either by collecting skin sloughed naturally by the whales, or by using biopsy darts fired from crossbows or compound bows. Sloughed skin was found frequently in warm waters, and particular samples could often be linked to photographs which enabled individuals to be identified. However, sloughed skin seemed less available at higher latitudes. Two types of darts were found to collect skin but collected samples were very small (<4 mm2) and insufficient for repeated DNA fingerprinting analyses. Sperm whales always reacted to darting by “startling” and showing changes of behavior over the next few minutes, but we found no indications of longer-term effects. In warm water studies, collection of sloughed skin seems to be generally effective, but for samples of sperm whale tissue at high latitudes modifications could probably be made to either of the darts in order to obtain larger-sized samples.

Obtaining skin samples from living sperm whales

Population estimate and inter-island movement of sperm whales, Physeter macrocephalus, in the Eastern Caribbean Sea

Drug metabolising N-acetyltransferase activity in human cell lines

There is evidence that active sonar exposure can have significant impacts on some cetacean species at relatively low levels (Evans and England, 2003; Evans and Miller, 2004). Beaked whales in particular are vulnerable to serious impacts including mortality from exposure to mid-frequency active sonar (1-10 kHz) (Jepson et al., 2003; Fernandez et al., 2004, 2005; Jaber et al., 2005; Fernandez, 2006; Cox et al., 2006). This year, the ECS reaffirmed its 2003 Statement of Concern on Marine Mammals and Noise, noting further that the development of scientific knowledge since 2003 underscores the need for taking urgent action on sonar mitigation. Current mitigation efforts are generally untested and insufficient for beaked whales.

/pdf/technical-report-on-effective-mitigation-for-active-sonar-5e8yy0nkj7.pdf

Technical Report on Effective Mitigation for Active Sonar & Beaked Whales

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