Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis

The role of histone hyperacetylation in regard to growth, differentiation, and apoptosis in colon cancer cells was assessed in an in vitro model system. HT-29 cells were grown in +/-10% fetal bovine serum with either 5 mM sodium butyrate or 0.3 microM trichostatin A [single dose (T) or 3 doses 8 h apart (TR)] for 24 h. Serum-starved HT-29 cells were further treated with epidermal growth factor or insulin-like growth factor I for an additional 24 h. Apoptosis was quantified with propidium iodide and characterized by electron microscopy. Northern blot analyses were performed with cDNA probes specific for intestinal alkaline phosphatase, Na-K-2Cl cotransporter, the cell cycle inhibitor p21, and the actin control. Flow cytometric analysis revealed a time-dependent growth suppression along with early induction of p21 mRNA in the butyrate, T, and TR groups. Histone hyperacetylation, assessed by acid-urea-triton gel electrophoresis, was transient in the T group but persisted for up to 24 h in the butyrate and TR groups. Induction of apoptosis, growth factor unresponsiveness, and differentiation occurred in the butyrate- and TR-treated cells but not those treated with a single dose of trichostatin A. Thus transient hyperacetylation of histones is sufficient to induce p21 expression and produce cellular growth arrest, but prolonged histone hyperacetylation is required for induction of the programs of differentiation, apoptosis, and growth factor unresponsiveness.     

Expanding networks: Signaling components in and a hypothesis for the evolution of metamorphosis

Metamorphosis is a substantial morphological transition between2 multicellular phases in an organism's life cycle, often markingthe passage from a prereproductive to a reproductive life stage.It generally involves major physiological changes and a shiftin habitat and feeding mode, and can be subdivided into an extendedphase of substantial morphological change and/or remodeling,and a shorter-term phase (for example, marine invertebrate "settlement,"insect "adult eclosion," mushroom fruiting body emergence) wherethe actual habitat shift occurs. Disparate metamorphic taxadiffer substantially with respect to when the habitat shiftoccurs relative to the timing of the major events of morphogeneticchange. I will present comparative evidence across a broad taxonomicscope suggesting that longer-term processes (morphogenetic changes)are generally hormonally regulated, whereas nitric oxide (NO)repressive signaling often controls the habitat shift itself.Furthermore, new evidence from echinoids (sea urchins, sanddollars) indicates a direct connection between hormonal andNO signaling during metamorphosis. I incorporate 2 hypothesesfor the evolution of metamorphosis—one involving heterochrony,the other involving phenotypic integration and evolutionarilystable configurations (ESCs)—into a network model formetamorphosis in echinoderms (sea urchins, starfish, and theirkin). Early indications are that this core regulatory networkcan be acted upon by natural selection to suit the diverse ecologicalneeds of disparate metamorphic organisms, resulting in evolutionaryexpansions and contractions in the core network. I briefly speculateon the ways that exposure to xenobiotic pollutants and othercompounds might influence successful settlement of juvenilesin the wild. Indeed, environmentally regulated life historytransitions—such as settlement, metamorphosis, and reproductivematuration—may be developmental periods that are especiallysensitive to such pollutants.     

Plasticity and constraints in development and evolution

Morphological similarities between organisms may be due to either homology or homoplasy. Homologous structures arise by common descent from an ancestral form, whereas homoplasious structures are independently derived in the respective lineages. The finding that similar ontogenetic mechanisms underlie the production of the similar structures in both lineages is not sufficient evidence of homology, as such similarities may also be due to parallel evolution. Parallelisms are a class of homoplasy in which the two lineages have come up with the same solution independently using the same ontogenetic mechanism. The other main class of homoplasy, convergence, is superficial similarity in morphological structures in which the underlying ontogenetic mechanisms are distinct. I argue that instances of convergence and parallelism are more common than is generally realized. Convergence suggests flexibility in underlying ontogenetic mechanisms and may be indicative of developmental processes subject to phenotypic plasticity. Parallelisms, on the other hand, may characterize developmental processes subject to constraints. Distinguishing between homology, parallelisms and convergence may clarify broader taxonomic patterns in morphological evolution.