Aims The aim of this study was to compare the effects of aspirin on platelet function as measured by the 'classical' template bleeding time with a new ex vivo method measuring closure times using the PFA-100@ machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo. Methods The trial was a randomized, double-blind, placebo-controlled crossover design, with each volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days, with an 18 day wash-out period between treatments. Bleeding times and closure times were measured before the first dose on the first day and 0.5 h after the last dose on the fifth day of each treatment period. They were also measured 2 weeks after the last day of the trial. Results Baseline bleeding times ( pre-placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s using the PFA-100@. Aspirin treatment caused an increase of both the template bleeding time (61%) and the closure time of the PFA-100@ (79%) when compared with the effects of placebo. The platelet aggregatory response to arachidonic acid was completely inhibited following aspirin treatment and was unaffected following placebo. Two weeks after the end of the trial, all values had returned to pre-treatment levels. The template bleeding time was unaltered in 1 of the 12 volunteers during aspirin treatment and was significantly prolonged in 3 of the 12 volunteers during placebo treatment. The PFA-100@ closure time was unaltered in 1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject during placebo treatment. Conclusions The change in closure time using the PFA-100@ is as sensitive and reproducible to the effects of aspirin on platelet function as is the template bleeding time test. However, the PFA-100@ produced less variable effects with fewer false positive results.
To investigate developmental responses to chronic hypoxia, we incubated alligator eggs at 17% O2 and 21% O2 for the entire course of embryonic development and for 5 months post-hatching. Hypoxic-incubated alligators hatched later and at a smaller size. Hematocrit was significantly higher in hypoxic-incubated animals immediately post-hatch. Allosteric modification of hemoglobin oxygen affinity did not appear to play a role in the adaptation to hypoxia, given equal nucleotide triphosphate-to-hemoglobin ratios in the hypoxic and normoxic groups. When acutely exposed to 21% O2, hypoxic-incubated alligators maintained oxygen consumption relative to their normoxic siblings despite their lower mass.
The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."
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