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Greater Resistance (greater + resistance)
Selected AbstractsDesert shrub water relations with respect to soil characteristics and plant functional typeFUNCTIONAL ECOLOGY, Issue 3 2002J. S. Sperry Summary 1.,Soil characteristics influence plant communities in part through water relations. Hypothetically, finer textured soils in arid climates should be associated with more negative plant and soil water potentials during drought, greater resistance of xylem to cavitation, and shallower root systems than coarse soils. 2.,These hypotheses were tested by comparing the water relations of Great Basin shrubs growing in sand versus loam soils. The eight study species (Chrysothamnus nauseosus, Chrysothamnus viscidiflorus, Chrysothamnus parryi, Tetradymia glabrata, Atriplex canescens, Atriplex confertifolia, Grayia spinosa and Sarcobatus vermiculatus) varied in typical rooting depth and vegetative phenology. 3.,Xylem pressures for a species were, on average, 1·1 MPa more negative in the loam versus the sand site, despite greater precipitation at the loam site. Root xylem at the loam site was, on average, 0·9 MPa more resistant to cavitation than at the sand site for the same species. There was a strong trend for shallower rooting depths at the loam versus the sand site. Within a species, roots were consistently more vulnerable to cavitation than stems, and experienced more cavitation during the growing season. 4.,Over most of the summer there was much more cavitation at the loam site than at the sand site. More than 80% loss of xylem conductivity (PLC) was estimated in shallow roots of three species at the loam site by the end of July, with two of the three showing extensive leaf drop and branch mortality. Transpiration rate was negatively correlated with PLC, with a tendency for lower gas-exchange rates in loam versus sand. 5.,At the sand site, cavitation resistance was negatively correlated with estimated rooting depth. Drought-deciduous species had the shallowest root systems and greatest resistance to cavitation. In contrast, two species with phreatophytic tendencies were summer-active and were the most vulnerable to cavitation. 6.,The cavitation resistance of roots determines the minimum water potential permitting hydraulic contact with soil. Differences in cavitation resistance of roots between desert species may contribute to differences in sensitivity of gas exchange to soil drought, ability to perform hydraulic lift, and response to late summer rain pulses. [source] Ecological implications of xylem cavitation for several Pinaceae in the Pacific Northern USAFUNCTIONAL ECOLOGY, Issue 5 2000J. Piñol Abstract 1.,Xylem hydraulic properties and vulnerability to cavitation (determined using the air-injection method) were studied in six Pinaceae of the northern Rocky Mountains: Pinus ponderosa, Pseudotsuga menziesii, Larix occidentalis, Pinus contorta, Pinus albicaulis and Abies lasiocarpa. We tested whether species extending into drier habitats exhibited increased resistance to water stress-induced cavitation, and whether there is a trade-off between xylem transport capacity and resistance to cavitation. 2.,At lower elevations the more drought-tolerant P. ponderosa was much less resistant to cavitation than the codominant P. menziesii. Greater vulnerability to cavitation in P. ponderosa was compensated for, at least in part, by increased stomatal control of water loss (inferred from carbon isotope discrimination) and by increased sapwood to leaf area ratios. Similar differences, but less pronounced, were found in codominant species at higher elevations. 3.,Leaf specific hydraulic conductivity was negatively correlated with mean cavitation pressure. When species were separated into pines and non-pines, sapwood specific conductivity and mean cavitation pressure were also negatively correlated within each of the two groups. 4.,Our results indicate that within the evergreen conifers examined, greater resistance to water stress-induced cavitation is not required for survival in more xeric habitats, and that there is a trade-off between xylem conductance and resistance to cavitation. [source] Resistance to tearing of calf and ostrich pericardium: Influence of the type of suture material and the direction of the suture lineJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2004José María García Páez Abstract The tearing of the valve leaflet of a cardiac bioprosthesis can cause early failure of this device, which is employed to replace a diseased native valve. This report involves the study of the behavior of 312 tissue samples (152 of calf pericardium and 160 of ostrich pericardium) treated with glutaraldehyde and subsequently subjected to tear testing. The samples were cut in the two principal directions: longitudinally, or root to apex, and transversely. They included a series of control samples that were left unsutured, and the remaining samples were repaired with the use of two different suture techniques: a running suture in the direction of the load and a telescoping suture perpendicular to the load. Four commercially available suture materials were employed: Pronova®, nylon, Gore-Tex®, or silk. The unsutured control samples of both types of pericardium exhibited a similar anisotropic behavior in the tear test. The mean resistance to tearing of the calf pericardium was 24.29 kN m in samples cut longitudinally and 34.78 kN m in those cut transversely (p = .03); the values were 28.08 kN m and 37.12 kN m (p = .002), respectively, in ostrich pericardium. The series repaired with the telescoping suture always exhibited greater resistance to tearing, with values that ranged between 44.34 and 64.27 kN for the samples of calf pericardium and from 41.65 to 47.65 kN for those obtained from ostrich. These assays confirm the anisotropic behavior of calf and ostrich pericardium treated with glutaraldehyde when subjected to tear testing, as well as the loss of this behavior in ostrich pericardium after suturing. Suturing techniques, such as the telescoping model, that provide a greater resistance to tearing should be studied for use in the design of the valve leaflets of cardiac bioprostheses made of biological materials. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 125,134, 2004 [source] Dental plaque: biological significance of a biofilm and community life-styleJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2005P. D. Marsh Abstract Background: Most microorganisms in nature attach to surfaces and form matrix-embedded biofilms. Biofilms are highly structured and spatially organized, and are often composed of consortia of interacting microorganisms, termed microbial communities, the properties of which are more than the sum of the component species. Microbial gene expression alters markedly in biofilms; organisms communicate by gene transfer and by secretion of diffusible signalling molecules. Cells in biofilms are less susceptible to antimicrobial agents. Aim and Materials & Methods: To comprehensively review the literature to determine whether dental plaque displays properties consistent with those of a typical biofilm and microbial community. Results: Novel microscopic and molecular techniques have demonstrated that plaque has a structured architecture with an extracellular matrix, and a diverse composition (around 50% of cells are unculturable). The constituent species communicate by gene transfer, by secreted peptides (Gram-positive bacteria) and autoinducer-2 (Gram-positive and Gram-negative bacteria). These organisms are functionally organized for increased metabolic efficiency, greater resistance to stress and for enhanced virulence. Plaque formation has direct and indirect effects on gene expression. Conclusion: Dental plaque displays properties that are typical of biofilms and microbial communities in general, a clinical consequence of which is a reduced susceptibility to antimicrobial agents as well as pathogenic synergism. [source] Evolutionary biology of starvation resistance: what we have learned from DrosophilaJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 5 2007S. RION Abstract Most animals face periods of food shortage and are thus expected to evolve adaptations enhancing starvation resistance (SR). Most of our knowledge of the genetic and physiological bases of those adaptations, their evolutionary correlates and trade-offs, and patterns of within- and among-population variation, comes from studies on Drosophila. In this review, we attempt to synthesize the various facets of evolutionary biology of SR emerging from those studies. Heritable variation for SR is ubiquitous in Drosophila populations, allowing for large responses to experimental selection. Individual flies can also inducibly increase their SR in response to mild nutritional stress (dietary restriction). Both the evolutionary change and the physiological plasticity involve increased accumulation of lipids, changes in carbohydrate and lipid metabolism and reduction in reproduction. They are also typically associated with greater resistance to desiccation and oxidative stress, and with prolonged development and lifespan. These responses are increasingly seen as facets of a shift of the physiology towards a ,survival mode', which helps the animal to survive hard times. The last decade has seen a great progress in revealing the molecular bases of induced responses to starvation, and the first genes contributing to genetic variation in SR have been identified. In contrast, little progress has been made in understanding the ecological significance of SR in Drosophila; in particular it remains unclear to what extent geographical variation in SR reflect differences in natural selection acting on this trait rather than correlated responses to selection on other traits. Drosophila offers a unique opportunity for an integrated study of the manifold aspects of adaptation to nutritional stress. Given that at least some major molecular mechanisms of response to nutritional stress seem common to animals, the insights from Drosophila are likely to apply more generally than just to dipterans or insects. [source] Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenoneAGING CELL, Issue 1 2007James M. Harper Summary Fibroblast cell lines were developed from skin biopsies of eight species of wild-trapped rodents, one species of bat, and a group of genetically heterogeneous laboratory mice. Each cell line was tested in vitro for their resistance to six varieties of lethal stress, as well as for resistance to the nonlethal metabolic effects of the mitochondrial inhibitor rotenone and of culture at very low glucose levels. Standard linear regression of species-specific lifespan against each species mean stress resistance showed that longevity was associated with resistance to death induced by cadmium and hydrogen peroxide, as well as with resistance to rotenone inhibition. A multilevel regression method supported these associations, and suggested a similar association for resistance to heat stress. Regressions for resistance to cadmium, peroxide, heat, and rotenone remained significant after various statistical adjustments for body weight. In contrast, cells from longer-lived species did not show significantly greater resistance to ultraviolet light, paraquat, or the DNA alkylating agent methylmethanesulfonate. There was a strong correlation between species longevity and resistance to the metabolic effects of low-glucose medium among the rodent cell lines, but this test did not distinguish mice and rats from the much longer-lived little brown bat. These results are consistent with the idea that evolution of long-lived species may require development of cellular resistance to several forms of lethal injury, and provide justification for evaluation of similar properties in a much wider range of mammals and bird species. [source] Analysis of the incidence of infectious pancreatic necrosis mortality in pedigreed Atlantic salmon, Salmo salar L., populationsJOURNAL OF FISH DISEASES, Issue 11 2006D R Guy Abstract A total of 77 124 Atlantic salmon post-smolts, representing 197 full-sib families produced by 149 males and 197 females, experienced a field challenge from infectious pancreatic necrosis virus (IPNV), following transfer to three separate seawater sites. The first IPN mortality was observed 45 days after transfer, and the duration of the epidemic varied between 37 and 92 days among sites. Mortalities were traced to their parental families by PIT (Passive Integrated Transpondes) tag records and DNA genotyping. Full-sib family mean incidence of mortality was calculated for each family on each site. Heritabilities were estimated based on the heterogeneity of chi-square using incidence within half-sib families and the variance in incidence among full-sib families, both on the observed and underlying liability scale. The observed correlation among families across sites was used to estimate genetic correlations. The overall mortality rate was 10.8%, with only small differences between sites, ranging from 10.3% to 11.9%. Heritabilities on the liability scale were found to be moderate to strong, and ranged between 0.24 and 0.81, with a pooled estimate of 0.43, greater than is typically associated with disease traits. Genetic correlations among sites were all substantial, between 0.71 and 0.78, and indicated that a substantial component of the genetic variation displayed within sites was common to all. The results show that field challenges can yield very good genetic information on family differences in resistance, especially when replicated over sites, which may then be developed for use in selection for breeding strains of Atlantic salmon with greater resistance to IPN. [source] Oxygen isotope analysis of phosphate: improved precision using TC/EA CF-IRMS,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2009D. F. LaPorte Abstract Oxygen isotope values of biogenic apatite have long demonstrated considerable promise for paleothermometry potential because of the abundance of material in the fossil record and greater resistance of apatite to diagenesis compared to carbonate. Unfortunately, this promise has not been fully realized because of relatively poor precision of isotopic measurements, and exceedingly small size of some substrates for analysis. Building on previous work, we demonstrate that it is possible to improve precision of ,18OPO4 measurements using a ,reverse-plumbed' thermal conversion elemental analyzer (TC/EA) coupled to a continuous flow isotope ratio mass spectrometer (CF-IRMS) via a helium stream [Correction made here after initial online publication]. This modification to the flow of helium through the TC/EA, and careful location of the packing of glassy carbon fragments relative to the hot spot in the reactor, leads to narrower, more symmetrically distributed CO elution peaks with diminished tailing. In addition, we describe our apatite purification chemistry that uses nitric acid and cation exchange resin. Purification chemistry is optimized for processing small samples, minimizing isotopic fractionation of PO4,3 and permitting Ca, Sr and Nd to be eluted and purified further for the measurement of ,44Ca and 87Sr/86Sr in modern biogenic apatite and 143Nd/144Nd in fossil apatite. Our methodology yields an external precision of ± 0.15, (1,) for ,18OPO4. The uncertainty is related to the preparation of the Ag3PO4 salt, conversion to CO gas in a reversed-plumbed TC/EA, analysis of oxygen isotopes using a CF-IRMS, and uncertainty in constructing calibration lines that convert raw ,18O data to the VSMOW scale. Matrix matching of samples and standards for the purpose of calibration to the VSMOW scale was determined to be unnecessary. Our method requires only slightly modified equipment that is widely available. This fact, and the demonstrated improvement in precision, should help to make apatite paleothermometry far more accessible to paleoclimate researchers. Copyright © 2009 John Wiley & Sons, Ltd. [source] Gliding characteristics of tendon repair in canine flexor digitorum profundus tendonsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2001Chunfeng Zhao The gliding resistance between the flexor digitorum profundus (FDP) tendon and the proximal pulley system was measured using the method of S. Uchiyama, J.H. Coert, L. Berglund, P.C. Amadio, K.N. An (J. Orthop. Res. 13 (1995) 83) in 108 adult dog digits in vitro. The FDP tendons were then lacerated to 80% of their transverse section. Each tendon was repaired with one of the following six suture techniques: Kessler, modified Kessler, Savage, Lee, Becker and simple running suture alone. Each repaired tendon was then tested again using the same method. The Student,Newman,Keuls test for multiple comparisons was performed for statistical analysis. The average gliding resistances of the Kessler, Savage, and Becker repairs were significantly greater than the resistances of the Lee, modified Kessler, and running suture alone repairs (P < 0.05). The Lee suture technique had a significantly greater resistance than the modified Kessler repair and the running suture (P < 0.05). The results of the peak gliding resistance followed the same trends, except that the modified Kessler repair was significantly higher than the running suture alone (P < 0.05). Suture techniques with a multi-strand core suture, with knots located outside the tendon surface, and with multiple-loops on the tendon surface may result in increased gliding resistance between the tendon and pulley system after tendon repair. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] 1-Methylcyclopropene affects the antioxidant system of apricots (Prunus armeniaca L. cv. Búlida) during storage at low temperatureJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 4 2010Isabel Egea Abstract BACKGROUND: Apricots (Prunus armeniaca cv. Búlida) were treated with 1 mL L,1 1-methylcyclopropene (1-MCP) immediately after harvest and stored in air at 2 °C for 21 days. Antioxidant levels (ascorbic acid and carotenoids), enzymatic antioxidant activities (superoxide dismutase (SOD) and unspecific peroxidase (POX)) and total antioxidant capacity (trolox equivalent antioxidant capacity (TEAC)) were determined. The level of oxidative stress was also established by measuring ion leakage during storage. The changes in the antioxidant potential of apricots were related to the capacity of 1-MCP to increase their commercial life. RESULTS: 1-MCP-treated fruits exhibited higher SOD activity, whereas POX activity was significantly higher only after 21 days at 2 °C. Treated fruits also exhibited better retention of ascorbate and carotenoids and higher TEAC during storage. In accordance with these observations, lower ion leakage values were detected in 1-MCP-treated apricots. CONCLUSION: Taken together, these results suggest that 1-MCP conferred a greater resistance to oxidative stress. This, along with the reduction in ethylene production, could contribute to the increase in commercial life and nutritional value observed in 1-MCP-treated apricots. Copyright © 2010 Society of Chemical Industry [source] An Arabidopsis thaliana ABC transporter that confers kanamycin resistance in transgenic plants does not endow resistance to Escherichia coliMICROBIAL BIOTECHNOLOGY, Issue 2 2008Kellie Burris Summary Concerns have been raised about potential horizontal gene transfer (HGT) of antibiotic resistance markers (ARMs) from transgenic plants to bacteria of medical and environmental importance. All ARMs used in transgenic plants have been bacterial in origin, but it has been recently shown that an Arabidopsis thaliana ABC transporter, Atwbc19, confers kanamycin resistance when overexpressed in transgenic plants. Atwbc19 was evaluated for its ability to transfer kanamycin resistance to Escherichia coli, a kanamycin-sensitive model bacterium, under simulated HGT, staged by subcloning Atwbc19 under the control of a bacterial promoter, genetically transforming to kanamycin-sensitive bacteria, and assessing if resistance was conferred as compared with bacteria harbouring nptII, the standard kanamycin resistance gene used to produce transgenic plants. NptII provided much greater resistance than Atwbc19 and was significantly different from the no-plasmid control at low concentrations. Atwbc19 was not significantly different from the no-plasmid control at higher concentrations. Even though HGT risks are considered low with nptII, Atwbc19 should have even lower risks, as its encoded protein is possibly mistargeted in bacteria. [source] Photocatalytic Coatings for Environmental Applications,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Norman S. Allen ABSTRACT A series of nano- and micronparticle-grade anatase and rutile titanium dioxide pigments have been prepared with various densities of surface treatments, particle size and surface area. Their photocatalytic activities have been determined in a series of paint films by FTIR, chalking, color, gloss change and weight loss after artificial weathering. The pigments have also been examined by rapid assessment methodologies using photodielectric microwave spectroscopy, 2-propanol oxidation and hydroxyl analysis. The microwave response under light and dark cycles provides an extended timescale probe of chargecarrier dynamics in the pigments. Pigment particle size, surface area and properties clearly play an important role in dispersion and any polymer-pigment interactions. Photooxidation studies on several types of paint films show a clear demarcation between nanoparticle- and pigmentary-grade titanium dioxide, with the former being more active because of their greater degree of catalytic surface activity. The photosensitivity of titanium dioxide is considered to arise from localized sites on the crystal surface (i.e. acidic OH), and occupation of these sites by surface treatments inhibits photoreduction of the pigment by ultraviolet radiation; hence, the destructive oxidation of the binder is inhibited. Coatings containing 2,5% by weight alumina or alumina and silica are satisfactory for generalpurpose paints. If greater resistance to weathering is desired, the pigments are coated more heavily to about 7,10% weight. The coating can consist of a combination of several materials, e.g. alumina, silica, zirconia, aluminum phosphates of other metals. For example, the presence of hydrous alumina particles lowers van der Waals forces between pigments particles by several orders of magnitude, decreasing particle-particle attractions. Hydrous aluminum oxide phases appear to improve dispersibility more effectively than most of the other hydroxides and oxides. Coated nanoparticles are shown to exhibit effective light stabilization in various water- and oilbased paint media in comparison with conventional organic stabilizers. Hindered piperidine stabilizers are shown to provide no additional benefits in this regard, often exhibiting strong antagonism. The use of photocatalytic titania nanoparticles in the development of self-cleaning paints and microbiological surfaces is also demonstrated in this study. In the former case, surface erosion is shown to be controlled by varying the ratio of admixture of durable pigmentary-grade rutile (heavily coated) and a catalytic-grade anatase nanoparticle. For environmental applications in the development of coatings for destroying atmospheric pollutants such as nitrogen oxide gases (NOX), stable substrates are developed with photocatalytic nanoparticle-grade anatase. In this study, porosity of the coatings through calcium carbonate doping is shown to be crucial in the control of the effective destruction of atmospheric NOx gases. For the development of microbiological substrates for the destruction of harmful bacteria, effective nanoparticle anatase titania is shown to be important, with hydrated high surface area particles giving the greatest activity. [source] Lifetime sexual dimorphism in Juniperus communis var. communisPLANT SPECIES BIOLOGY, Issue 1 2007LENA K. WARD Abstract The sexes of dioecious Juniperus communis were differentially affected over their lifetime in response to ecological and physiological stress in populations of different ages studied over 23 years in southern England. In a young population, the female survival rate was less than the male rate, with more females dying during a severe attack by rabbits and later with fungus disease in the roots. The sex ratio (female : male) in marked individuals was predicted by age, changing from 1:1.13 in 1983 to 1:1.32 in 2005. In an old senescing population, where two-thirds of the individuals died, the sex ratio varied, but overall became more male biased (1:1.51,1:2.10). Males had a greater resistance to terminal disease, and were slightly older than females at death (110 years compared to 106). Young females grew less than males, presumably because of greater trade-offs with reproductive effort: the mean annual shoot growth was 6.7 cm compared to 8.1 cm in males. By approximately 30 years of age, heights of the sexes were significantly different. The annual growth of old females (4.8 cm) was greater than that in males (4.3 cm), possibly because males survived longer in poor health. Sexual differences in height in the old population were progressively lost. Cone abundance in females was less than that in males and cone production had greater periodicity; the young population outperformed the old. There were slightly longer time lags in inverse correlations between growth and reproductive indices in females. [source] NOS2 (iNOS) Deficiency in Kidney Donor Accelerates Allograft Loss in a Murine ModelAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007C. Du Renal NOS2 is expressed and produces abundant nitric oxide (NO) in various renal cells in response to proinflammatory cytokines. However, the role of this enzyme in renal allograft survival remains unknown. Kidney allotransplantation was performed in the murine model of C57BL/6J (H-2d) to nephrectomized Balb/c (H-2b) mice. Here we show that deficiency in NOS2 expression in kidney donors significantly advanced allograft failure, indicated by decreasing mean survival of recipients receiving NOS2 null grafts (15.4 ± 6.4 days) as compared to those with wild type grafts (65.4 ± 28.1 days) (p = 0.0005). Consistent with survival results, NOS2 null grafts had more severe renal tubule injury and decreased renal function compared to wild type grafts. In vitro NOS2 expressing TEC had greater resistance to allogeneic lymphocyte-mediated apoptosis. The addition of exogenous NO inhibited Fas-mediated TEC apoptosis and reduced proliferation of allogeneic lymphocytes. These data suggest that endogenous production of NO through renal NOS2 activity can play a protective role in kidney grafts through attenuating Fas-mediated donor cell apoptosis as well as by inhibiting proliferation of inflammatory infiltrating lymphocytes. Enhanced donor NOS2 expression may be a useful strategy to improve kidney transplant survival. [source] Increased number and function of FoxP3 regulatory T cells during experimental arthritisARTHRITIS & RHEUMATISM, Issue 12 2008Kristen Monte Objective CD4+CD25+FoxP3+ regulatory T (Treg) cells are critical regulators of autoimmunity. Yet the number of Treg cells is paradoxically increased in rheumatoid arthritis (RA) patients, and Treg cells show variable activity in human studies. The objective of this study was to characterize the expansion and function of Treg cells during the initiation and progression of experimental arthritis. Methods To unequivocally identify Treg cells, we crossed FoxP3gfp mice with K/BxN mice to generate arthritic mice in which Treg cells express green fluorescence protein. We examined the expansion and function of Treg cells and effector T (Teff) cells during different stages of arthritis, using flow cytometry and cell proliferation analyses. Results In K/BxN mice, thymic selection of KRN T cells resulted in an enrichment of forkhead box P3 (FoxP3),positive Treg cells. Treg cell numbers increased during arthritis, with significant increases in spleens and draining lymph nodes, indicating selective tropism to sites of disease. In contrast to the in vitro unresponsiveness of Treg cells when cultured alone, substantial proportions of Treg cells proliferated in both nonarthritic and arthritic mice. However, they also underwent greater apoptosis, thereby maintaining equilibrium with Teff cells. Similarly, enhanced Treg cell,suppressive activity during arthritis was offset by greater resistance by their Teff cell counterparts and antigen-presenting cells. Conclusion In this well-established model of RA, the interplay of Teff cells and Treg cells in K/BxN mice recapitulated many features of the human disease. We demonstrated an ordered expansion of Treg cells during arthritis and dynamic changes in Treg cell and Teff cell functions. By elucidating factors that govern Treg cell and Teff cell development in K/BxNgfp mice, we will gain insight into the pathophysiology of and develop novel therapeutics for human RA. [source] Pharmacokinetics and metabolism of the novel synthetic C -nucleoside, 1-(2-deoxy- , -D-ribofuranosyl)-2,4-difluoro- 5-iodobenzene: a potential mimic of 5-iodo-2,-deoxyuridineBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2002Panteha Khalili Abstract 1-(2-Deoxy- , -D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (5-IDFPdR) is one of the several unnatural 1-(2-deoxy- , -D-ribofuranosyl)-2,4-difluoro-5-substituted-benzenes recently synthesized for evaluation as anticancer, antiviral and diagnostic imaging agents. This class of C -nucleosides was designed to exploit several potential advantages relative to classical 5-substituted-2,-deoxyuridines, including stability towards phosphorolysis by pyrimidine phosphorylase, increased lipophilicity that may alter their ability to cross the blood,brain-barrier, and a greater resistance towards catabolism and deiodination. The physiochemical evaluation of 5-IDFPdR showed high lipophilicity (log P=2.8), moderately high protein binding (70,75%), stability towards phosphorolysis (e.g. no evidence of metabolic deglycosylation) by thymidine phosphorylase, and minimal microsomal metabolism in vitro. Pharmacokinetic studies of 5-IDFPdR in rat were characterized by a short elimination half-life (9,12 min), modest urinary elimination in pooled 0,24 h urine specimens (10,14%, including 2% as unconjugated drug) and high oral bioavailability (F=0.96). Both glucuronide and sulfate metabolites were present in urine. Glucuronidation was the predominant conjugation pathway. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||||||||