The pearl oysters, Pinctada maxima and P margaritifera, respond in different ways to culture in dissimilar environments

Growth, Condition Index (CI) and survival of the pearl oysters, Pinctada maxima and R margaritifera, were measured in three size groups of oysters over 14 months at two dissimilar environments in the Great Barrier Reef lagoon. These were the Australian Institute of Marine Science (AIMS) in a mainland bay and Orpheus Island Research Station (OIRS) in coral reef waters. Temperature, suspended particulate matter (SPM) and particulate organic matter (POM) were monitored during the study. Temperature at AIMS fluctuated more widely than at OIRS both daily and seasonally, with annual ranges 20-31 degrees C and 22-30 degrees C, respectively. Mean SPM concentration at AIMS (11.1 mg l(-1)) was much higher than at OIRS (1.4 mg l(-1)) and fluctuated widely (2-60 mg l(-1)). Mean POM level was also substantially higher at AIMS, being 2.1 mg l(-1) compared with 0.56 mg l(-1) at OIRS. Von Bertalatiffy growth curve analyses showed that P. maxima grew more rapidly and to larger sizes than P. margaritifera at both sites. For the shell height (SH) of R maxima, growth index phi'=4.31 and 4.24, asymptotic size SHinfinity = 229 and 205 mm, and time to reach 120 mm SH (T-(120))= 1.9 and 2.1 years at AIMS and OIRS, respectively. While for P margaritifera, phi'=4.00 and 4.15, SHinfinity = 136 and 157 mm, and T-(120) = 2.5 and 3.9 years at AIMS and OIRS, respectively. R maxima had significantly lower growth rates and lower survival of small oysters during winter compared with summer. There were, however, no significant differences between the two sites in growth rates of P. maxima and final Cl values. In contrast, P. margaritifiera showed significant differences between sites and not seasons, with lower growth rates, survival of small oysters, final Cl values and asymptotic sizes at AIMS. The winter low temperatures, but not high SPM at AIMS, adversely affected P. maxima. Conversely, the high SPM levels at AIMS, but not temperature, adversely affected P. margaritifera. This was in accordance with earlier laboratory-based energetics studies of the effects of temperature and SPM on these two species. P maxima has potential to be commercially cultured in ca. > 25 degrees C waters with a wide range of SPM levels, including oligotrophic coral reef waters with appropriate particle sizes. It is possible to culture R margaritifera in turbid conditions, but its poor performance in these conditions makes commercial culture unlikely. (c) 2005 Elsevier B.V. All rights reserved.

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.

Reply to comment by A. G. J. Hilberts and P. A. Troch on "Influence of capillarity on a simple harmonic oscillating water table: Sand column experiments and modeling"

We thank Hilberts and Troch [2006] for their comment on our paper [Cartwright et al, 2005]. Before proceeding with our specific replies to the comments we would first like to clarify the definitions and meanings of equations (1)-(3) as presented by Hilberts and Troch [2006]. First, equation (1) is the fundamental definition of the (complex) effective porosity as derived by Nielsen and Perrochet [2000]. Equations (2) and (3), however, represent the linear frequency response function of the water table in the sand column responding to simple harmonic forcing. This function, which was validated by Nielsen and Perrochet [2000], provides an alternative method for estimating the complex effective porosity from the experimental sand column data in the absence of direct measurements of h_(tot) (which are required if equation (1) is to be used).

Investigation of the coordinated functional activities of cytochrome P450 3A4 and P-glycoprotein in limiting the absorption of xenobiotics in Caco-2 cells

The coordination of the functional activities of intestinal CYP3A4 and P-gp in limiting the absorption of xenobiotics in Caco-2 cells was investigated. Growing Caco-2 cells were exposed to increasing concentrations of doxorubicin (1-2 μM) in plastic flasks to encourage a subpopulation of cells, that displayed an intrinsically higher multidrug resistance (mdr) phenotype than the parent cells, to survive and grow. Doxorubicin-exposed (hereinafter referred to as type I cells) and nonexposed Caco-2 cells (parent cells) on collagen-coated inserts were also treated with either 0 (control) or 0.25 μM 1α,25-dihydroxyvitamin D3 to promote cellular CYP3A4 expression. Increased P-gp protein expression, as detected by Western blotting, was noted in type I cells (213±54.35%) compared to that of parent cells (100±6.05%). Furthermore, they retained significantly less [3H]vincristine sulphate (p<0.05), a P-gp substrate, after efflux (272.89±11.86 fmol/mg protein) than the parent cells (381.39±61.82 fmol/mg protein). The expression of CYP3A4 in parental cells after 1α,25-dihydroxyvitamin D3 treatment was quantified to be 76.2±7.6 pmol/mg protein and comparable with that found in human jejunal enterocytes (70.0±20.0 pmol/mg protein). Type I cells, however, expressed a very low quantity of CYP3A4 both before and after the treatment that was beyond the minimum detection limit of Western blotting. Functionally, the rates of 1-hydroxylation of midazolam by CYP3A for both cell types ranged from 257.0±20.0 to 1057.0±46.0 pmol/min/mg protein. Type I cells, although having a higher P-gp expression and activity comparatively, metabolized midazolam less extensively than the parent cells. The results suggested that there were noncoordinated functional activities of intestinal CYP3A4 and P-gp in Caco-2 cells, although they both functioned independently to minimize intestinal epithelial absorption of xenobiotics. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.

Pulse compression applied to the detection of F.S.K. and P.S.K. signals

The matched filter detector is well known as the optimum detector for use in communication, as well as in radar systems for signals corrupted by Additive White Gaussian Noise (A.W.G.N.). Non-coherent F.S.K. and differentially coherent P.S.K. (D.P.S.K.) detection schemes, which employ a new approach in realizing the matched filter processor, are investigated. The new approach utilizes pulse compression techniques, well known in radar systems, to facilitate the implementation of the matched filter in the form of the Pulse Compressor Matched Filter (P.C.M.F.). Both detection schemes feature a mixer- P.C.M.F. Compound as their predetector processor. The Compound is utilized to convert F.S.K. modulation into pulse position modulation, and P.S.K. modulation into pulse polarity modulation. The mechanisms of both detection schemes are studied through examining the properties of the Autocorrelation function (A.C.F.) at the output of the P.C.M.F.. The effects produced by time delay, and carrier interference on the output A.C.F. are determined. Work related to the F.S.K. detection scheme is mostly confined to verifying its validity, whereas the D.P.S.K. detection scheme has not been reported before. Consequently, an experimental system was constructed, which utilized combined hardware and software, and operated under the supervision of a microprocessor system. The experimental system was used to develop error-rate models for both detection schemes under investigation. Performances of both F. S. K. and D.P. S. K. detection schemes were established in the presence of A. W. G. N. , practical imperfections, time delay, and carrier interference. The results highlight the candidacy of both detection schemes for use in the field of digital data communication and, in particular, the D.P.S.K. detection scheme, which performed very close to optimum in a background of A.W.G.N.

Methodology for development of a physiological model incorporating CYP3A and P-glycoprotein for the prediction of intestinal drug absorption

The small intestine poses a major barrier to the efficient absorption of orally administered therapeutics. Intestinal epithelial cells are an extremely important site for extrahepatic clearance, primarily due to prominent P-glycoprotein-mediated active efflux and the presence of cytochrome P450s. We describe a physiologically based pharmacokinetic model which incorporates geometric variations, pH alterations and descriptions of the abundance and distribution of cytochrome 3A and P-glycoprotein along the length of the small intestine. Simulations using preclinical in vitro data for model drugs were performed to establish the influence of P-glycoprotein efflux, cytochrome 3A metabolism and passive permeability on drug available for absorption within the enterocytes. The fraction of drug escaping the enterocyte (F(G)) for 10 cytochrome 3A substrates with a range of intrinsic metabolic clearances were simulated. Following incorporation of P-glycoprotein in vitro efflux ratios all predicted F(G) values were within 20% of observed in vivo F(G). The presence of P-glycoprotein increased the level of cytochrome 3A drug metabolism by up to 12-fold in the distal intestine. F(G) was highly sensitive to changes in intrinsic metabolic clearance but less sensitive to changes in intestinal drug permeability. The model will be valuable for quantifying aspects of intestinal drug absorption and distribution.