bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic toxicity and body residues of the nonpolar narcotic 1,2,3,4-tetrachlorobenzene in Chironomus riparius
Authors: Leslie Heather A. , Kraak Michiel H. S. , Hermens Joop L. M.
Published: November 2004

The use of internal concentrations as a doseparameter for baseline toxicity requires an understanding of the relationship between accumulation level and toxic effects, not only for acute but also for chronic exposure. In this study of chronic toxicity of the nonpolar narcotic 1,2,3,4-tetrachlorobenzene (TeCB) to Chironomus riparius, the chronic median lethal concentration (LC50) was determined to be 0.99 (0.54–1.82) μM, the median sublethal effect concentration (EC50) for growth was 0.76 (0.73–0.97) μM, and the chronic (sublethal) no-observed-effect concentration (NOEC) was 0.24 ± 0.01 μM. An acute-to-chronic ratio of 9.8 was calculated from a previously determined acute LC50 value and this NOEC. The chronic critical body residue (CBR), 136 mmol/kg lipid, was the same as the acute CBR, previously determined. The similarity of the chronic and acute CBRs lends support to the exposure time independent aspect of baseline toxicity theory. An implication of this is that internal concentrations estimated by biomimetic sampling devices may be compared to acute CBR data to determine chronic baseline toxicity risk. Such sampling devices, solid-phase microextraction (SPME) fibers, were simultaneously exposed during the toxicity test. The results of this study suggest that body residues estimated with SPME may be used to predict baseline toxicity for various exposure durations.
Water-extractability, free ion activity, and pH explain cadmium sorption and toxicity to Folsomia candida (Collembola) in seven soil-pH combinations
Authors: van Gestel Cornelis A. M. , Koolhaas Josée E.
Published: November 2004

Toxicity of cadmium to Folsomia candida was determined in soils at different pHs (3.5, 5.0, and 6.5). The Langmuir sorption constant (KL), based on pore-water or water-extractable concentrations, showed a pH-related increase of cadmium sorption that was most pronounced when using free Cd2+ ion activities ({Cd2+}s). Two-species Langmuir isotherms that used total cadmium concentration ([Cd]) or {Cd2+} and pH in the water-extractable fractions gave the best description of cadmium sorption on all soils together. Cadmium concentrations causing 50% reduction of growth and reproduction (median effective concentrations [EC50s]) differed by a factor of 4.5 to 20 when based on total soil concentrations and increased with increasing pH. However, when based on water-extractable or pore-water [Cd] or {Cd2+}, EC50s decreased with increasing pH, but differences between soils were still a factor of 4.5 to 32. The EC50s differed by less than a factor of 2.2 when based on body [Cd] in the surviving animals. Two-species Langmuir isotherms were used to relate body [Cd] in survivors to {Cd2+}, corrected for pH in water-extractable or pore-water fractions. An excellent description of effects on growth and reproduction was found when related to the body concentrations predicted in this way; the difference in EC50s between soils was reduced to a factor <2. This demonstrates that F. candida is mainly exposed to cadmium through the soil solution, and suggests that principles of a biotic ligand model approach may be applicable for this soil organism.
Organophosphorus pesticides in storm-water runoff from southern California (USA)
Authors: Schiff Kenneth , Sutula Martha
Published: November 2004

Large quantities of the organophosphorus (OP) pesticides diazinon and chlorpyrifos are applied to California (USA) watersheds every year, but few data are available on the sources of OP pesticides in urban watersheds. The goal of this study was to characterize diazinon and chlorpyrifos concentrations from different land uses indicative of source categories in urban southern California watersheds. This characterization included analysis of 128 runoff samples from eight different land uses over five storm events. Diazinon was consistently detected (93% of samples) during this study, whereas chlorpyrifos was not consistently detected (12% of samples). The mixed agricultural land use had the highest flow weighted mean (FWM) concentration of diazinon (4,076 ng/L), which exceeded the next-highest land-use categories (commercial and residential) by one to two orders of magnitude (324–99 ng/L, respectively). Open space had the lowest concentration of diazinon (<20 ng/L). Concentrations of diazinon at replicate land-use sites and during replicate storm events at the same site were highly variable. The difference in diazinon FWM concentrations among replicate sites ranged from 1.5-fold to 45-fold. The difference in diazinon FWM concentrations among storms at the same site ranged from 1.25-fold to 30-fold. Part of this variability is a response to the temporal patterns observed within a storm event. The majority of land-use site-events had peak concentrations before peak flow indicating a first-flush effect, but this was not always a predictable temporal trend. The first-flush effect was rarely evident in terms of mass loadings because flows can range orders of magnitude during a single event in highly impervious urban watersheds. Flow variability thus overwhelms the variability in diazinon concentrations attributable to the first-flush effect.
Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South Africa
Authors: Hecker Markus , Giesy John P. , Jones Paul D. , Jooste Alarik M. , Carr James A. , Solomon Keith R. , Smith Ernest E. , Van Der Kraak Glen , Kendall Ronald J. , du Preez Louis
Published: November 2004

Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3,000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point.
Dynamic in-stream fate modeling of xenobiotic organic compounds: A case study of linear alkylbenzene sulfonates in the Lambro River, Italy
Authors: Deksissa Tolessa , De Pauw Dirk , Vanrolleghem Peter A.
Published: November 2004

Using a conceptual hydraulic model, a one-dimensional dynamic river water quality model has been developed to assess the short-term fate of linear alkylbenzene sulfonates (LAS) in the river compartments water and benthic sediment. The model assumes local equilibrium sorption and that both dissolved and sorbed chemical are available for biodegradation. To investigate the interaction of nutrient dynamics and organic contaminant fate, the model is coupled with a basic water quality model. On the basis of the Lambro River (Italy) as a case study, the result shows that the model predictions agree well with the measured data set. The model output sensitivity to model parameters has been tested, and the results depict that the model is highly sensitive to the biodegrading parameters. Also, a comparison of a steady state with a dynamic simulation and the effect of nutrient dynamics on the LAS fate in the Lambro River as a scenario analysis are presented. The results indicate the usefulness of the proposed model for the short-term simulation of organic contaminant fate in unsteady environmental conditions.
Effects of trichloroethylene and perchloroethylene on wild rodents at Edwards Air Force Base, California, USA
Authors: Spring Sarah E. , Miles A. Keith , Anderson Michael J.
Published: November 2004

Effects of inhalation of volatilized trichloroethylene (TCE) or perchloroethylene (PCE) were assessed based on the health and population size of wild, burrowing mammals at Edwards Air Force Base (CA, USA). Organic soil-vapor concentrations were measured at three sites with aquifer contamination of TCE or PCE of 5.5 to 77 mg/L and at two uncontaminated reference sites. Population estimates of kangaroo rats (Dipodomys merriami and D. panamintinus) as well as hematology, blood chemistry, and histopathology of kangaroo rats and deer mice (Peromyscus maniculatus) were compared between contaminated and uncontaminated populations. Maximum soil-gas concentrations associated with groundwater contamination were less than 1.5 μl/L of TCE and 0.07 μl/L of PCE. Population estimates of kangaroo rats were similar at contaminated and reference sites. Hematology, blood chemistry, and histopathology of kangaroo rats and deer mice indicated no evidence of health effects caused by exposure. Trichloroethylene or PCE in groundwater and in related soil gas did not appear to reduce the size of small mammal populations or impair the health of individuals.
Effect of extraction conditions on trace element solubilization in deposit feeder digestive fluid
Authors: Weston Donald P. , Judd Jeffrey R. , Mayer Lawrence M.
Published: November 2004

In vitro extraction of sediments using digestive fluid of deposit-feeding invertebrates has been advocated as a measure of in vivo bioavailability, but the standard procedure used for the extractions alters fluid properties relative to in vivo conditions. In vivo fluid properties (redox potential [Eh], pH, dissolved oxygen) were measured in the gut of the polychaete Arenicola brasiliensis, and then the effects of gut evacuation, elevated temperature, and atmospheric exposure on these properties and/or metal and metalloid extraction capability of the fluid was assessed. The midgut of A. brasiliensis has an electropositive Eh of about +170 to +230 mV, a neutral pH, and little or no dissolved oxygen. Exposure to the atmosphere during in vitro extraction increased gut fluid oxygen content and affected the ability of the fluid to extract some trace elements from sediment particles, particularly Pb, Ni, Cu, Mn, and As. Even for these substances, however, the effects of oxygen exposure on extractability by gut fluid typically were small (<2-fold difference in amount extracted). For Cr, Hg, Se, Cd, Fe, and Zn, the effects of oxygen exposure usually were minor and inconsistent in direction. Maintaining anaerobic conditions during in vitro contaminant extractions is necessary when the experimental objective is to mimic accurately in vivo conditions and predict trace element extraction in the gut. If using metal extractability as a relative measure for sediment risk assessment purposes, a high degree of accuracy may not be required, and aerobic in vitro extractions could be suitable and produce only minor errors in extractability relative to in vivo conditions.
Pesticides in mountain yellow-legged frogs (Rana muscosa) from the Sierra Nevada Mountains of California, USA
Authors: Fellers Gary M. , McConnell Laura L. , Pratt David , Datta Seema
Published: November 2004

In 1997, pesticide concentrations were measured in mountain yellow-legged frogs (Rana muscosa) from two areas in the Sierra Nevada Mountains of California, USA. One area (Sixty Lakes Basin, Kings Canyon National Park) had large, apparently healthy populations of frogs. A second area (Tablelands, Sequoia National Park) once had large populations, but the species had been extirpated from this area by the early 1980s. The Tablelands is exposed directly to prevailing winds from agricultural regions to the west. When an experimental reintroduction of R. muscosa in 1994 to 1995 was deemed unsuccessful in 1997, the last 20 (reintroduced) frogs that could be found were collected from the Tablelands, and pesticide concentrations in both frog tissue and the water were measured at both the Tablelands and at reference sites at Sixty Lakes. In frog tissues, dichlorodiphenyldichloroethylene (DDE) concentration was one to two orders of magnitude higher than the other organochlorines (46 ± 20 ng/g wet wt at Tablelands and 17 ± 8 Sixty Lakes). Both γ-chlordane and trans-nonachlor were found in significantly greater concentrations in Tablelands frog tissues compared with Sixty Lakes. Organophosphate insecticides, chlorpyrifos, and diazinon were observed primarily in surface water with higher concentrations at the Tablelands sites. No contaminants were significantly higher in our Sixty Lakes samples.
Barramundi as an indicator species for environmental monitoring in north Queensland, Australia: Laboratory versus field studies
Authors: Codi Susan , Humphrey Craig , Klumpp David , Delean Steven
Published: November 2004

The dose-response relationship for hepatic 7-ethoxyresorufin-O-deethylase (EROD) induction in barramundi (Lates calcarifer) was examined under controlled laboratory conditions for 15 d using farm-reared barramundi. These results were compared with EROD activity measured in barramundi collected from two rivers catchments (impacted and nonimpacted) in northern Queensland, Australia. Barramundi were dosed by intraperitoneal injection with a known cytochrome P4501A (CYP1A) inducer, β-naphthoflavone (β-NF), at 5, 10, and 50 mg kg−1 using two controls: A vehicle control (corn-oil injected) and an experimental control (no injection). The EROD induction occurred within 4 h in the 5, 10, and 50 mg β-NF kg−1 exposures, reaching mean maximum activities of 88.6 (±51.9), 85.5 (±91.7), and 149.1 (±106.4) pmol min−1 mg protein−1, respectively. Mean EROD activities remained low in the corn-oil controls (2.1 ± 1.8 pmol min−1 mg protein−1) and experimental controls (5.3 ± 4.4 pmol min−1 mg protein−1) throughout the study. Barramundi demonstrated a rapid response curve, which was dose dependent (50 > 10 > 5 mg β-NF kg−1) and decreased progressively over time from induction. Measurement of total cytochrome P450 content (nmol mg protein−1) was not dose dependent. The EROD activities from field-collected barramundi from the Johnstone River (impacted) and Olive River (nonimpacted) suggest exposure to low-level contaminants in the Johnstone River fish only. With more controlled laboratory and field studies, barramundi have the potential to become a major indicator species in assessing exposure to environmental contaminants in coastal areas throughout northern Queensland, Australia.
Occurrence and fate of pharmaceuticals and alkylphenol ethoxylate metabolites in an effluent-dominated river and wetland
Authors: Gross Birgit , Montgomery-Brown John , Naumann Anneke , Reinhard Martin
Published: November 2004

The occurrence of pharmaceuticals, nonylphenol ethoxylate metabolites, and other wastewater-derived contaminants in surface waters is a potential environmental concern, especially since the discovery of contaminants with endocrine-disrupting properties. The present study investigated the discharge of emerging contaminants into the Santa Ana River (CA, USA) and their attenuation during river transport and passage through a constructed wetland. Contaminants studied included pharmaceuticals (gemfibrozil, ibuprofen, naproxen, ketoprofen, and carbamazepine) and their metabolites, hormones, the metabolites of alkylphenol polyethoxylates (APEMs), N-butyl benzenesulfonamide (NBBS), and chlorinated tris-propylphosphates (TCPPs). The APEMs included alkylphenols (APs), short-chain AP polyethoxylates (APEOs), AP polyethoxycarboxylates (APECs), and carboxylated APECs (CAPECs). In wastewater treatment plant effluent, APECs and CAPECs represented the dominant APEM fraction (1.8–18.7 μg/L), whereas APEOs and APs contributed only small amounts to the overall APEM concentrations (0.10–0.92 and ≤0.1 μg/L, respectively) except where the effluent was infiltrated into soil (5.2 μg/L). In effluents, ibuprofen and its metabolites, TCPPs, and NBBS were detected regularly (<0.5 μg/L), and the other pharmaceuticals were detected occasionally. Transport in the Santa Ana River for 11 km resulted in the significant attenuation of all contaminants, from 67% for gemfibrozil to 100% for others. Wetland treatment (residence time, 2–4 d) resulted in partial removal of ibuprofen, gemfibrozil, and TCPPs and transformed APEOs to APECs.
Toxicity of glyphosate-based pesticides to four North American frog species
Authors: Howe Christina M. , Berrill Michael , Pauli Bruce D. , Helbing Caren C. , Werry Kate , Veldhoen Nik
Published: November 2004

Gyphosate-basedherbicides are among the most widely used pesticides in the world. We compared the acute toxicity of the glyphosate end-use formulation Roundup Original® to four North American amphibian species (Rana clamitans, R. pipiens, R. sylvatica, and Bufo americanus) and the toxicity of glyphosate technical, the polyethoxylated tallowamine surfactant (POEA) commonly used in glyphosate-based herbicides, and five newer glyphosate formulations to R. clamitans. For R. clamitans, acute toxicity values in order of decreasing toxicity were POEA > Roundup Original > Roundup Transorb® > Glyfos AU®; no significant acute toxicity was observed with glyphosate technical material or the glyphosate formulations Roundup Biactive®, Touchdown®, or Glyfos BIO®. Comparisons between the four amphibian species showed that the toxicity of Roundup Original varied with species and developmental stage. Rana pipiens tadpoles chronically exposed to environmentally relevant concentrations of POEA or glyphosate formulations containing POEA showed decreased snout-vent length at metamorphosis and increased time to metamorphosis, tail damage, and gonadal abnormalities. These effects may be caused, in some part, by disruption of hormone signaling, because thyroid hormone receptor β mRNA transcript levels were elevated by exposure to formulations containing glyphosate and POEA. Taken together, the data suggest that surfactant composition must be considered in the evaluation of toxicity of glyphosate-based herbicides.
Enzymatic and estrogenic responses in fish exposed to organic pollutants in the New York-New Jersey (USA) Harbor Complex
Authors: Mcardle Margaret E. , Mcelroy Anne E. , Elskus Adria A.
Published: November 2004

This study examines biochemical and hormonal responses in resident and migratory fish from the New York-New Jersey (USA) Harbor Complex (NY-NJHC) and those treated with sediment-associated organic contaminants. Following laboratory exposures to organic extracts of NY-NJHC sediments (injection), livers from adult male mummichogs, Fundulus heteroclitus, were analyzed for vitellogenin (VTG), cytochrome P4501A (CYP1A), CYP3A, and estradiol 2-hydroxylase (E2OHase) and ethoxyresorufin-O-deethylase (EROD) activities. Levels of CYP1A (311–391% of control) and EROD (267–361% of control) were elevated in mummichogs exposed to high doses of sediment extracts, while VTG, CYP3A, and E2OHase were unaffected. In field studies, reproductively mature male mummichogs collected from a highly contaminated area, Newark Bay (NJ, USA), did not have detectable levels of VTG but did exhibit elevated levels of CYP1A and EROD. Vitellogenin was also not detected in juvenile striped bass (Morone saxatilis) collected from the main stem of the lower Hudson River (NY, USA). Similar to results in the sediment extract- treated fish, CYP3A and E2OHase were unaltered in Newark Bay F. heteroclitus. The lack of response of CYP3A and E2OHase activities to contaminant mixtures, either environment or sediment derived, suggests that compounds in these mixtures either do not alter these enzymes, produce antagonistic effects in mixtures, are present at ineffective concentrations, or are regulated in a species-specific manner.
Health symptoms and exposure to organophosphate pesticides in farmworkers
Authors: Strong Larkin L. , Thompson Beti , Coronado Gloria D. , Griffith William C. , Vigoren Eric M. , Islas Ilda
Published: November 2004

Background

Few studies have examined the relationship between reported health symptoms and exposure to organophosphate (OP) pesticides.

Methods

Fisher's exact test was used to assess the relationship between self‐reported health symptoms and indicators of exposure to OP pesticides in 211 farmworkers in Eastern Washington.

Results

The health symptoms most commonly reported included headaches (50%), burning eyes (39%), pain in muscles, joints, or bones (35%), a rash or itchy skin (25%), and blurred vision (23%). Exposure to pesticides was prevalent. The proportion of detectable samples of various pesticide residues in house and vehicle dust was weakly associated with reporting certain health symptoms, particularly burning eyes and shortness of breath. No significant associations were found between reporting health symptoms and the proportion of detectable urinary pesticide metabolites.

Conclusions

Certain self‐reported health symptoms in farmworkers may be associated with indicators of exposure to pesticides. Longitudinal studies with more precise health symptom data are needed to explore this relationship further. Am. J. Ind. Med. 46:599–606, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of UBV photometry in selected area 133
Authors: Karataş Y. , Bilir S. , Karaali S. , Ak S. G.
Published: November 2004

We interpret the de‐reddened UBV data for the field SA 133 to deduce the stellar density and metallicity distribution functions. The logarithmic local space density for giants, D*(0) = 6.40, and the agreement of the luminosity function for dwarfs and sub‐giants with the one of Hipparcos confirms the empirical method used for their separation. The metallicity distribution for dwarfs gives a narrow peak at [Fe/H] = +0.13 dex, due to apparently bright limiting magnitude, Vo = 16.5, whereas late‐type giants extending up to z ∼ 4.5 kpc from the galactic plane have a multimodal distribution. The metallicity distribution for giants gives a steep gradient d[Fe/H]/dz = –0.75 dex kpc–1 for thin disk and thick disk whereas a smaller value for the halo, i.e. d[Fe/H]/dz = –0.45 dex kpc–1. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the class of Oe stars'
Authors: Negueruela I. , Steele I. A. , Bernabeu G.
Published: November 2004

We present high‐quality spectra of the majority of stars that have been classified as Oe and find that their published spectral types are generally too early, most likely due to infilling of He I lines. As a matter of fact, all stars classified as Oe actually fall inside the range O9–B0 with the important exception of HD 155806 (O7.5 III) and perhaps HD 39680 (difficult to classify, but likely O8.5V). Observations of a sample of objects with published spectral types in the O9–B0 range previously classified as peculiar or emission‐line stars fail to reveal any new Oe star with spectral type earlier than O9.5. Most objects classified as peculiar in “classical” literature show signs of binarity in our spectra, but no spectral anomalies. We conclude that there is likely a real decline in the fraction of Be stars for spectral types earlier than B0, not due to observational bias. The few Oe stars with spectral types earlier than O9.5 deserve detailed investigation in order to provide constraints on the physical reasons of the Be phenomenon. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Recombinational DNA repair: the ignored repair systems
Authors: Smith Kendric C.
Published: November 2004

The recent finding of a role for the recA gene in DNA replication restart does not negate previous data showing the existence of recA‐dependent recombinational DNA repair, which occurs when there are two DNA duplexes present, as in the case for recA‐dependent excision repair, for postreplication repair (i.e., the repair of DNA daughter‐strand gaps), and for the repair of DNA double‐strand breaks. Recombinational DNA repair is critical for the survival of damaged cells. BioEssays 26:1322–1326, 2004. © 2004 Wiley Periodicals, Inc.
PolyADP‐ribose polymerase‐1 (PARP‐1) and the evolution of learning and memory
Authors: Sung Ying‐Ju , Ambron Richard T.
Published: November 2004

PARP‐1 is a multifunctional enzyme that can modulate gene expression. Cohen‐Armon et al.1 found that a homologue of PARP‐1 is activated in the Aplysia nervous system as the animal responds to an aversive stimulus, which leads to sensitization, and during a more complex form of learning that involves feeding behavior. Significantly, inhibiting PARP‐1 activation blocked the learning. Several key pathways in Aplysia neurons are activated both during learning and after injury, suggesting that mechanisms of learning evolved from primitive responses to injury. Since PARP‐1 is evolutionarily conserved as a responder to various forms of stress, the finding that PARP‐1 is activated during learning supports this idea. BioEssays 26:1268–1271, 2004. © 2004 Wiley Periodicals, Inc.
Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion bioreactor: Part I. Cell density, viability, and cell‐cycle distribution
Authors: Dalm Marcella C.F. , Cuijten Suzanne M.R. , van Grunsven Wout M.J. , Tramper Johannes , Martens Dirk E.
Published: November 2004

For the development of optimal perfusion processes the effect of the feed and bleed rate on cell growth in a perfusion bioreactor was studied. The viable‐cell density, viability, growth, death, and lysis rate and cell‐cycle distribution of a hybridoma cell line producing an IgG1 were studied over a range of specific feed and bleed rates. It was found that the feed and bleed rates applied in the different cultures could be divided into two regions based on the viable‐cell density and cell‐cycle distribution. The cultures in the first region, low feed rates (0.5 and 1.0 d−1) combined with low bleed rates (0.05 and 0.10 d−1), were nutrient‐limited, as an increase in the feed rate resulted in an increase in the viable‐cell density. The cultures in the second region, high feed and bleed rates, were nonnutrient‐limited. In this region the viable‐cell density decreased more or less linearly with an increase in the bleed rate and was independent of the feed rate. This suggests that the cells were limited by a cell‐related factor. Comparison of Trypan‐blue dye‐exclusion measurements and lactate‐dehydrogenase activity measurements revealed that cell lysis was not negligible in this bioreactor set‐up. Therefore, lactate‐dehydrogenase activity measurements were essential to measure the death rate accurately. The specific growth rate was nearly constant for all tested conditions. The viability increased with an increase of the bleed rate and was independent of the feed rate. Furthermore, the specific productivity of monoclonal antibody was constant under all tested conditions. For the optimal design of a perfusion process it should first be established whether viability is an important parameter. If not, a bleed rate as low as possible should be chosen. If low viabilities are to be avoided, the bleed rate chosen should be higher, with the value depending on the desired viability. Next, the feed rate should be set at such a rate that the cells are just in the nonnutrient‐limited region. © 2004 Wiley Periodicals, Inc.
Ferrocenyl‐Modified DNA: Synthesis, Characterization and Integration with Semiconductor Electrodes
Authors: Pike Andrew R. , Ryder Lyndsey C. , Horrocks Benjamin R. , Clegg William , Connolly Bernard A. , Houlton Andrew
Published: November 2004

The ferrocenyl‐nucleoside, 5‐ethynylferrocenyl‐2′‐deoxycytidine (1) has been prepared by Pd‐catalyzed cross‐coupling between ethynylferrocene and 5‐iodo‐2′‐deoxycytidine and incorporated into oligonucleotides by using automated solid‐phase synthesis at both silica supports (CPG) and modified single‐crystal silicon electrodes. Analysis of DNA oligonucleotides prepared and cleaved from conventional solid supports confirms that the ferrocenyl‐nucleoside remains intact during synthesis and deprotection and that the resulting strands may be oxidised and reduced in a chemically reversible manner. Melting curve data show that the ferrocenyl‐modified oligonucleotides form duplex structures with native complementary strands. The redox potential of fully solvated ferrocenyl 12‐mers, 350 mV versus SCE, was shifted by +40 mV to a more positive potential upon treatment with the complement contrary to the anticipated negative shift based on a simple electrostatic basis. Automated solid‐phase methods were also used to synthesise 12‐mer ferrocenyl‐containing oligonucleotides directly at chemically modified silicon <111> electrodes. Hybridisation to the surface‐bound ferrocenyl‐DNA caused a shift in the reduction potential of +34 mV to more positive values, indicating that, even when a ferrocenyl nucleoside is contained in a film, the increased density of anions from the phosphate backbone of the complement is still dominated by other factors, for example, the hydrophobic environment of the ferrocene moiety in the duplex or changes in the ferrocene–phosphate distances. The reduction potential is shifted >100 mV after hybridisation when the aqueous electrolyte is replaced by THF/LiClO4, a solvent of much lower dielectric constant; this is consistent with an explanation based on conformation‐induced changes in ferrocene–phosphate distances.
Car–Parrinello Molecular Dynamics Study of the Initial Dinitrogen Reduction Step in Sellmann‐Type Nitrogenase Model Complexes
Authors: Kirchner Barbara , Reiher Markus , Hille Andreas , Hutter Jürg , Hess Bernd A.
Published: November 2004

We have studied reduction reactions for nitrogen fixation at Sellmann‐type model complexes with Car–Parrinello simulation techniques. These dinuclear complexes are especially designed to emulate the so‐called open‐side FeMoco model. The main result of this work shows that in order to obtain the reduced species several side reactions have to be suppressed. These involve partial dissociation of the chelate ligands and hydrogen atom transfer to the metal center. Working at low temperature turns out to be one necessary pre‐requisite in carrying out successful events. The successful events cannot be described by simple reaction coordinates. Complicated processes are involved during the initiation of the reaction. Our theoretical study emphasizes two experimental strategies which are likely to inhibit the side reactions. Clamping of the two metal fragments by a chelating phosphane ligand should prevent dissociation of the complex. Furthermore, introduction of tert‐butyl substituents could improve the solubility and should thus allow usage of a wider range of (mild) acids, reductants, and reaction conditions.
Six‐ and Eightfold Palladium‐Catalyzed Cross‐Coupling Reactions of Hexa‐ and Octabromoarenes
Authors: Stulgies Baldur , Prinz Peter , Magull Jörg , Rauch Karsten , Meindl Kathrin , Rühl Stephan , de Meijere Armin
Published: November 2004

Palladium‐catalyzed sixfold coupling of hexabromobenzene (20) with a variety of alkenylboronates and alkenylstannanes provided hexaalkenylbenzenes 1 in up to 73 % and 16 to 41 % yields, respectively. In some cases pentaalkenylbenzenes 21 were isolated as the main products (up to 75 %). Some functionally substituted hexaalkenylbenzene derivatives containing oxygen or sulfur atoms in each of their six arms have also been prepared (16 to 24 % yield). The sixfold coupling of the less sterically encumbered 2,3,6,7,10,11‐hexabromotriphenylene (24) gave the desired hexakis(3,3‐dimethyl‐1‐butenyl)triphenylene (25) in 93 % yield. The first successful cross‐coupling reaction of octabromonaphthalene (26) gave octakis‐(3,3‐dimethyl‐1‐butenyl)naphthalene (27) in 21 % yield. Crystal structure analyses disclose that, depending on the nature of the substituents, the six arms are positioned either all on the same side of the central benzene ring as in 1 a and 1 i, making them nicely cup‐shaped molecules, or alternatingly above and below the central plane as in 1 h and 23. In 27, the four arms at C‐1,4,6,7 are down, while the others are up, or vice versa. Upon catalytic hydrogenation, 1 a yielded 89 % of hexakis(tert‐butylethyl)benzene (23). Some efficient accesses to alkynes with sterically demanding substituents are also described. Elimination of phosphoric acid from the enol phosphate derived from the corresponding methyl ketones gave 1‐ethynyladamantane (3 b, 62 % yield), 1‐ethynyl‐1‐methylcyclohexane (3 c, 85 %) and 3,3‐dimethylpentyne (3 e, 65 %). 1‐(Trimethylsilyl)ethynylcyclopropane (7) was used to prepare 1‐ethynyl‐1‐methylcyclopropane (3 d) (two steps, 64 % overall yield). The functionally substituted alkynes 3 f–h were synthesized in multistep sequences starting from the propargyl chloride 11, which was prepared in high yields from the dimethylpropargyl alcohol 10 (94 %). The alkenylstannanes 19 were prepared by hydrostannation of the corresponding alkynes in moderate to high yields (42–97 %), and the alkenylboronates 2 and 4 by hydroboration with catecholborane (27–96 % yield) or pinacolborane (26–69 % yield).
Altering Hydrogen Storage Properties by Hydride Destabilization Through Alloy Formation: LiH and MgH2 Destabilized with Si.
Authors: Vajo John J. , Mertens Florian , Ahn Channing C. , Bowman Robert C. Jr. , Fultz Brent
Published: November 2004

For Abstract see ChemInform Abstract in Full Text.
Unsymmetrical Diaryl Sulfones and Aryl Vinyl Sulfones Through Palladium‐Catalyzed Coupling of Aryl and Vinyl Halides or Triflates with Sulfinic Acid Salts.
Authors: Cacchi Sandro , Fabrizi Giancarlo , Goggiamani Antonella , Parisi Luca M. , Bernini Roberta
Published: November 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Some New Fluorine Containing 1,3,4‐Oxadiazole Derivatives as Potential Antibacterial and Anticancer Agents.
Authors: Bhat K. Subrahmanya , Karthikeyan M. S. , Holla B. Shivarama , Shetty N. Suchetha
Published: November 2004

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Synthesis and Photochromic Properties of Methoxy Substituted 2,2‐Diaryl‐2H‐naphtho[1,2‐b]pyrans.
Authors: Gabbutt Christopher D. , Hepworth John D. , Heron B. Mark , Thomas David A. , Kilner Colin , Partington Steven M.
Published: November 2004

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Synthesis of 3‐(3‐Acetyl‐5‐aryl‐2,3‐dihydro‐1,3,4‐oxadiazol‐2‐yl)chromones
Authors: Cao L. , Zhang L. , Liu J. J.
Published: November 2004

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Synthesis of 3,5‐Difunctionalized 1‐Methyl‐1H‐pyrazolo [3,4‐b]Pyridines Involving Palladium‐Mediated Coupling Reactions.
Authors: Lavecchia G. , Berteina‐Raboin S. , Guillaumet G.
Published: November 2004

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1,2,4‐Triazines in Organic Synthesis. Part 25. Synthesis of Functionalized 1H‐Pyrazolo[4,3‐e][1,2,4]triazines and Their Fused Derivatives via ipso‐Substitution of Methylsulfonyl Group with O‐, N‐, S‐ and C‐Nucleophiles.
Authors: Mojzych Mariusz , Rykowski Andrzej
Published: November 2004

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Microwave Assisted Synthesis of Some New Isoxazolyltriazinan‐2‐ones.
Authors: Rajanarendar E. , Ramu K. , Srinivas M.
Published: November 2004

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A Suzuki—Miyaura Coupling Mediated Deprotection as Key to the Synthesis of a Fully Lipidated Malarial GPI Disaccharide.
Authors: Liu Xinyu , Seeberger Peter H.
Published: November 2004

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Two Successive One‐Pot Reactions Leading to the Expeditious Synthesis of (‐)‐Centrolobine.
Authors: Boulard Lucie , BouzBouz Samir , Cossy Janine , Franck Xavier , Figadere Bruno
Published: November 2004

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Synthesis of 2‐Acetyl‐4‐hydroxynaphtho[2,3‐b]pyran‐5,10‐dione and the 4‐Deoxy Analogue as Models for Comparative Biological Evaluations.
Authors: Ameer Farouk , Giles Robin G. F. , Green Ivan R. , Hugo Victor I. , Patel Samir , Pearce Rene
Published: November 2004

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Rapid Synthesis of Nanoparticles of Hexagonal Type In2O3 and Spherical Type Tl2O3 by Microwave Irradiation.
Authors: Patra Chitta Ranjan , Gedanken Aharon
Published: November 2004

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X‐Ray Absorption Spectroscopy of Low Temperature Fuel Cell Catalysts
Authors: Russell Andrea E. , Rose Abigail
Published: November 2004

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Seven‐Membered Rings
Authors: Bremner John B.
Published: November 2004

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Four‐Membered Ring Systems
Authors: Alcaide Benito , Almendros Pedro
Published: November 2004

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Biphasic Catalysis with Thermoregulated Ligands
Authors: Jin Zilin , Wang Yanhua , Jiang Jingyang , Wen Fei
Published: November 2004

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Cross Metathesis of Nitrogen‐Containing Systems
Authors: Vernall Andrea J. , Abell Andrew D.
Published: November 2004

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Comparative Quantitative Structure—Activity Relationship Studies (QSAR) on Non‐Benzodiazepine Compounds Binding to Benzodiazepine Receptor (BzR)
Authors: Hadjipavlou‐Litina D. , Garg Rajni , Hansch Corwin
Published: November 2004

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Copper(II) Complexes of Amino Acids and Peptides Containing Chelating Bis(imidazolyl) Residues
Authors: Sovago Imre , Osz Katalin , Varnagy Katalin
Published: November 2004

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Photoadducts of Metallic Compounds with Nucleic Acids — Role Played by the Photoelectron Transfer Process and by the TAP and HAT Ligands in the RuII Complexes
Authors: Blasius Romain , Moucheron Cecile , Kirsch‐De Mesmaeker Andree
Published: November 2004

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Three‐Dimensional Solution NMR Spectroscopy of Complex Structures and Mixtures
Authors: Rinaldi Peter L.
Published: November 2004

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Breast cancer risk in relation to different types of hormone replacement therapy in the E3N‐EPIC cohort
Authors: Fournier Agnès , Berrino Franco , Riboli Elio , Avenel Valérie , Clavel‐Chapelon Françoise
Published: November 2004

Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. A recent large cohort study showed effects of similar magnitude for different types of progestogens and for different routes of administration of estrogens evaluated. Further investigation of these issues is of importance. We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N‐EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow‐up (mean duration: 5.8 years). Data were analyzed using multivariate Cox proportional hazards models. In this cohort where the mean duration of HRT use was 2.8 years, an increased risk in HRT users compared to nonusers was found (relative risk (RR) 1.2 [95% confidence interval 1.1–1.4]). The RR was 1.1 [0.8–1.6] for estrogens used alone and 1.3 [1.1–1.5] when used in combination with oral progestogens. The risk was significantly greater (p <0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2–1.7] and 0.9 [0.7–1.2], respectively. When combined with synthetic progestins, both oral and transdermal/percutaneous estrogens use were associated with a significantly increased risk; for transdermal/percutaneous estrogens, this was the case even when exposure was less than 2 years. Our results suggest that, when combined with synthetic progestins, even short‐term use of estrogens may increase breast cancer risk. Micronized progesterone may be preferred to synthetic progestins in short‐term HRT. This finding needs further investigation. © 2004 Wiley‐Liss, Inc.
Parental occupational exposures and Ewing's sarcoma
Authors: Moore Lee E. , Gold Laura , Stewart Patricia A. , Gridley Gloria , Prince Jacqueline R. , Zahm Shelia Hoar
Published: November 2004

A case‐control study of Ewing's sarcoma (ES) was conducted to search for occupational exposures associated with ES. The study consisted of 196 cases and 196 random‐digit controls matched on geographical region, gender, ethnic origin and birth date. A questionnaire was administered to mothers of participants to obtain information on medical conditions, medications, and parental occupations during and after the index pregnancy. An occupational exposure expert coded jobs and industries for possible and probable exposure to selected occupational hazards. Risk of ES was increased with probable parental exposure to wood dusts during their usual occupation post pregnancy (odds ration [OR] = 3.2; 95% confidence interval [CI] = 1.1–9.2). Other exposures, including a priori suspected risk factors such as exposure to pesticides and farm animals, were not significantly associated with ES. A history of household pesticide extermination was associated with ES among boys aged 15 or younger (OR = 3.0; 95% CI = 1.1–8.1), but not among girls or older boys. Our results suggest that earlier reports of associations of ES with parental farm employment may have been describing risks associated with organic dusts encountered when working on a farm, rather than agricultural exposures or other farming related exposures. © 2004 Wiley‐Liss, Inc.
Multiple mechanisms downregulate CDKN1C in human bladder cancer
Authors: Hoffmann Michèle J. , Florl Andrea R. , Seifert Hans‐Helge , Schulz Wolfgang A.
Published: November 2004

Expression of the imprinted CDKN1C gene at chromosome 11p15.5 encoding the cell cycle inhibitor p57KIP2 is disturbed in Beckwith‐Wiedemann syndrome and in several human cancers by different mechanisms. Many advanced urothelial cancers (TCC) display downregulation of CDKN1C expression. The responsible mechanisms were investigated in TCC cell lines, with cultured normal urothelial cells (UEC) as controls. CDKN1C mRNA expression was diminished in 12/15 TCC lines and p57KIP2 protein was decreased accordingly. Because CDKN1C is expressed from the maternal allele only, LOH at 11p15.5 represents one mechanism of downregulation. In 3 cell lines, several polymorphic markers flanking CDKN1C were homozygous compatible with this mechanism. Hypermethylation of the CDKN1C promoter, a reported cause of downregulation in other cancers, was detected by bisulfite sequencing in several cell lines and appeared associated with downregulation in at least one cell line. The methylation inhibitor 5‐aza‐2′deoxycytidine induced CDKN1C expression in this cell line and others. A third reported mechanism involves a switch of both alleles toward a paternal imprinting pattern, indicated by hypomethylation of a differentially methylated region (DMR) in the imprinting center (IC2). This hypomethylation was detected in most TCC lines, and was associated with re‐expression of the non‐coding LIT1 RNA and with downregulation of CDKN1C in several. Thus, CDKN1C downregulation in TCC seems to occur by several different mechanisms. This finding and the ability of p57KIP2 to induce senescence in urothelial cells make CDKN1C a good candidate for a tumor suppressor at 11p in TCC. © 2004 Wiley‐Liss, Inc.
Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)
Authors: Machida Shizuo , Saga Yasushi , Takei Yuji , Mizuno Izumi , Takayama Takeshi , Kohno Takahiro , Konno Ryo , Ohwada Michitaka , Suzuki Mitsuaki
Published: November 2004

SU6668 (TSU‐68) is a small‐molecule synthetic inhibitor of the angiogenic related receptor tyrosine kinases Flk‐1/KDR, PDGFRβ, and FGFR1. Using a mouse model of peritoneally disseminated ovarian cancer, we investigated whether SU6668 inhibits peritoneal dissemination and prolongs survival time. BALB/c nude mice were intraperitoneally (i.p.) inoculated with SHIN‐3 (VEGF‐hypersecretory) or KOC‐2S (PDGF‐hypersecretory) ovarian serous adenocarcinoma cells with marked peritoneal dissemination ability. From the day after i.p. inoculation of tumor cells, SU6668 was orally administered 6 times weekly at a daily dose of 100 mg/kg or 400 mg/kg. The SU6668‐administered group and the vehicle‐administered control group were compared for the number of tumor vascular endothelial cells, weight of peritoneally disseminated tumors, amount of ascitic fluid and survival time. As a result, these 3 parameters were significantly smaller in the SHIN‐3‐inoculated, SU6668‐administered mice than in the control group (p = 0.03, p = 0.002, and p = 0.02, respectively). The mean survival time was significantly longer, at 58.1 ± 11.2 days, in the SU6668‐administered mice than that (34.5 ± 8.8 days) in the control group (p = 0.002). Similarly, in the KOC‐2S‐inoculated mice, the oral administration of SU6668 significantly reduced these 3 parameters (p = 0.04, p = 0.04, and p = 0.03, respectively), and significantly prolonged survival (16.6 ± 1.7 days vs. 11.0 ± 0.7 days, p = 0.008). Thus, the oral administration of SU6668 inhibited angiogenesis and peritoneal dissemination and prolonged survival in mice with peritoneally disseminated ovarian cancer. These effects were observed with both the VEGF‐ and PDGF‐hypersecretory cell lines. Our results suggest that molecular targeting with oral SU6668 will become a new therapeutic strategy targeting peritoneally disseminated ovarian cancer. © 2004 Wiley‐Liss, Inc.
Determination of didanosine in human serum by on‐line solid‐phase extraction coupled to high‐performance liquid chromatography with electrospray ionization tandem mass spectrometric detection: application to a bioequivalence study
Authors: Estrela Rita de Cassia E. , Salvadori Myriam C. , Raices Renata S. L. , Suarez‐Kurtz Guilherme
Published: November 2004

A method based on solid‐phase extraction coupled to liquid chromatography with positive ion electrospray ionization and tandem mass spectrometric detection was developed for the determination of didanosine in human serum, using lamivudine as internal standard. The acquisition was performed in the multiple reaction monitoring mode, monitoring the transitions m/z 237 → 136.7 for didanosine and m/z 230 → 111.7 for lamivudine. The method was linear over the range studied (10–1500 ng ml−1), with r2 > 0.98, and the run time was 5 min. The intra‐ and inter‐assay precisions were ≤10% and the intra‐ and inter‐assay accuracies were >95%. The absolute recoveries were 99.8% (10 ng ml−1), 98.4% (30 ng ml−1), 91.5% (700 ng ml−1) and 94.7% (1200 ng ml−1). The limits of detection and quantitation were 5 and 10 ng ml−1, respectively. The method was applied to a bioequivalence study, in which 24 healthy adult volunteers (12 men) received single oral doses (200 mg) of reference and test didanosine formulations (buffered powder for oral solutions), in an open, two‐way, randomized, crossover protocol. The 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax (peak serum concentration) and AUC0–inf (area under the serum concentration versus time curve from time zero to infinity) were within the range 80–125%, which supports the conclusion that the two formulations are bioequivalent regarding the rate and extent of didanosine absorption. Copyright © 2003 John Wiley & Sons, Ltd.