bluuebunny/crossref_metadata_2025 huggingface dataset:
6,6″-Azobis(2,2′-bipyridine) and Its Dinuclear Ruthenium Complex: A Comparative Study with Positional Isomers
Authors: Otsuki Joe , Kurihara Izumi , Imai Arata , Hamada Yuki , Omokawa Nobuyuki
Published: May 2007

The azobis(bipyridine) ligand 6,6″-azobis(2,2′-bipyridine) (6-azobpy) was prepared as a new member of the family of azopolypyridine derivatives. This compound undergoes reversible trans/cis photoisomerization. Reaction of 6-azobpy and [Ru(bpy)2Cl2] afforded a dinuclear complex [{Ru(bpy)2}2(μ-6-azobpy)]4+. An analogue with deuterated bpy fragments was also prepared to help clarify the 1H NMR signals in the part of the 6-azobpy ligand. The analysis of 1H NMR spectra clearly identified the structure of the complex, in which the Ru2+ ions are chelated by the bpy parts of the bridging 6-azobpy ligand. Electronic absorption and electrochemical properties are characterized by the presence of a low-lying π* level of the bridging ligand, manifested by a metal-to-ligand charge-transfer band extending down to 800 nm and by two consecutive one-electron reduction waves at relatively less negative potentials in cyclic voltammetry. These properties were compared with those of previously reported positional isomers with the help of density functional theory (DFT), time-dependent DFT, and ZINDO calculations. The analysis of the redox couple of Ru3+/2+ showed that the redox potentials differ slightly between the diastereomers and that there is an intermetallic electronic interaction.
Structural Characterization of a Dioxovanadium(V) Complex with 4,8-Dihydroxyquinoline-2-carboxylic Acid
Authors: Moriuchi Toshiyuki , Nishiyama Masahito , Beppu Tomohiko , Hirao Toshikazu , Rehder Dieter
Published: May 2007

4,8-Dihydroxyquinoline-2-carboxylic acid (1) possessing quinoline-N, hydroxy-O, and carboxy-O donor functions was demonstrated to serve as a tridentate ligand in the complexation with NH4VO3, affording the cis-dioxovanadium(V) complex 2. Each molecule of 2 was found to be packed in a hexagonal molecular arrangement through π–π interaction in the crystal packing, creating a channel cavity which was occupied by water molecules that form a one-dimensional water chain.
Synthesis, Structures, and Optical Properties of Two Novel Two-Photon Initiators Derived from 2,2′:6′,2″-Terpyridine
Authors: Hu Zhang-Jun , Yang Jia-Xiang , Tian Yu-Peng , Tao Xu-Tang , Tian Lei , Zhou Hong-Ping , Xu Gui-Bao , Yu Wen-Tao , Yan Yun-Xing , Sun Yuan-Hong , Wang Chuan-Kui , Yu Xiao-Qiang , Jiang Min-Hua
Published: May 2007

Efficient aqueous-phase aldol condensation, Michael addition, and solvent-free Wittig reactions were successfully employed to synthesize two two-photon initiators 9-ethyl-3-[4-(2,2′:6′,2″-terpyridinyl-4′-yl)styryl]carbazole (T1) and 9-{4-[4-(2,2′:6′,2″-terpyridinyl-4′-yl)styryl]phenyl}carbazole (T2). The two initiators with carbazolyl moiety attached to 2,2′:6′,2″-terpyridine present D–π–A-type framework, where A is a π-deficient terpyridine ring. The crystal structures were determined by single-crystal X-ray diffraction determination. The experimental results confirmed that the two initiators have sensitive single-photon-excited fluorescence (SPEF) and two-photon-excited fluorescence (TPEF) properties. The experimental and theoretical two-photon absorption (TPA) cross-sections were investigated. Two-photon initiation polymerization (TPIP) microfabrication experiments were carried out, and possible polymerization mechanisms are discussed based on the theoretical evaluation.
Effects of Basic Fibroblast Growth Factor and a Prostaglandin E2 Receptor Subtype 4 Agonist on Osteoblastogenesis and Adipogenesis in Aged Ovariectomized Rats
Authors: Aguirre J Ignacio , Leal Martha E , Rivera Mercedes F , Vanegas Sally M , Jorgensen Marda , Wronski Thomas J
Published: May 2007

bFGF stimulates osteo- and adipogenesis concurrently at skeletal sites with red but not with fatty marrow, whereas a PGE2 receptor subtype 4 agonist has bone anabolic effects at both skeletal sites and decreases adipose tissue within red and fatty marrow.

Introduction: Basic fibroblast growth factor (bFGF) stimulates osteogenesis at skeletal sites with hematopoietic but not with fatty marrow. The prostaglandin E2 (PGE2) receptor subtype 4 agonist (EP4A) stimulates osteogenesis at the former skeletal sites, but its effects at fatty marrow sites are unknown. In addition, both bFGF and PGE2 through the EP4 receptor have also been implicated in adipogenesis. However, their specific effects on bone marrow adipogenesis and the inter-relationship with osteogenesis have never been studied in vivo.

Materials and Methods: Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and maintained for 1 yr after surgery. OVX rats were then injected daily with bFGF or with EP4A SC for 3 wk. The osteo- and adipogenic effects of these agents were assessed by histomorphometry and by determining changes in expression of genes associated with these events by real-time PCR in the lumbar and caudal vertebrae, bones with a predominance of hematopoietic and fatty marrow, respectively. Expression of FGFR1–4 and the EP4 receptor were also evaluated by real-time PCR and immunocytochemistry.

Results: bFGF and EP4A stimulated bone formation at skeletal sites with hematopoietic marrow, but only the later anabolic agent is also effective at fatty marrow sites. The diminished bone anabolic effect of bFGF at the fatty marrow site was not caused by a lack of cell surface receptors for the growth factor at this site. Interestingly, whereas EP4A decreased fatty marrow area and the number of adipocytes, bFGF increased osteogenesis and adipogenesis within the bone marrow.

Conclusions: bFGF can stimulate osteogenesis and bone marrow adipogenesis concurrently at red marrow sites, but not at fatty marrow sites. In contrast, EP4A stimulates bone formation at skeletal sites with hematopoietic and fatty marrow and simultaneously decreased fatty marrow area and the number of adipocytes in the bone marrow, suggesting that osteogenesis occurs at the expense of adipogenesis.
Osteoporosis in Patients With Diabetes Mellitus
Authors: Hofbauer Lorenz C , Brueck Carolin C , Singh Shiv K , Dobnig Harald
Published: May 2007

Demographic trends with longer life expectancy and a lifestyle characterized by low physical activity and high-energy food intake contribute to an increasing incidence of diabetes mellitus and osteoporosis. Diabetes mellitus is a risk factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes mellitus may have impaired bone formation because of the absence of the anabolic effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus, vascular complications may account for low bone mass and increased fracture risk. Patients with type 2 diabetes mellitus display an increased fracture risk despite a higher BMD, which is mainly attributable to the increased risk of falling. Strategies to improve BMD and to prevent osteoporotic fractures in patients with type 1 diabetes mellitus may include optimal glycemic control and aggressive prevention and treatment of vascular complications. Patients with type 2 diabetes mellitus may additionally benefit from early visual assessment, regular exercise to improve muscle strength and balance, and specific measures for preventing falls.
Onset, Progression, and Plateau of Skeletal Lesions in Fibrous Dysplasia and the Relationship to Functional Outcome
Authors: Hart Elizabeth S , Kelly Marilyn H , Brillante Beth , Chen Clara C , Ziran Navid , Lee Janice S , Feuillan Penelope , Leet Arabella I , Kushner Harvey , Robey Pamela G , Collins Michael T
Published: May 2007

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy.

Introduction: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD.

Materials and Methods: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial 99Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed.

Results: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1–43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6–75) compared with 23.1 (range, 0.5–63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr.

Conclusions: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.
Sorption of uranyl(VI) cations on suspended silicate: effects ofN-donor ligands, carboxylic acids, organic cosolvents, and metal ions
Authors: Pathak P. N. , Choppin Gregory R.
Published: May 2007

Sorption of uranyl ion, UO22+, on silicate particles (3.00g/L) was studied in sodium perchlorate solution as a function of pcH and ionic strength at 298 K. The effects of different ligands (e.g.,N-donors, carboxylic acids) on the uranyl sorption were investigated. AtI= 0.20 M (NaClO4), uranyl sorption on silicate increased fromca.6% (pcH 3.0) toca.99% (at pcH 6.5), above which a small decrease was observed. A synergistic enhancement in uranyl sorption was observed in the presence ofN-donor ligands such as 1,10-phenanthroline and ethylenediamine in the pcH range 3 to 4.5 as compared to that in the absence of ligands. Carboxylic acids inhibited the sorption in the order: citric acid > malonic acid > nitrilotriacetic acid > iminodiacetic acid > sulfosalicylic acid > succinic acid > glycolic acid. The presence of organic cosolvents such as dimethylsulfoxide, glycerol and tetrahydrofuran had no significant influence on the uranyl sorption profile. Uranyl sorption decreased marginally in the presence of 1.00 × 10−3M Eu(III).
Application of oxidized multi-wall carbon nanotubes for Th(IV) adsorption
Authors: Chen C. L. , Li X. L. , Wang X. K.
Published: May 2007

Th(IV) adsorption onto oxidized multi-wall carbon nanotubes (MWCNTs) was carried out at 293±2K. The effects of MWCNT concentration, pH, and ionic strength were studied. The results showed that Th(IV) adsorption onto oxidized MWCNTs strongly depended on MWCNT concentration and pH, and was weakly dependent on ionic strength. Oxidized MWCNTs showed a higher Th(IV) adsorption capacity than as-grown MWCNTs. The adsorption process followed pseudo second order kinetics. The Freundlich isotherm model described the data better than the Langmuir model. The adsorption mechanism of Th(IV) may be surface complexation. Oxidized MWCNTs may be a promising candidate for the concentration of Th(IV), or its analogue actinides from large volumes.
Greatly reduced bioavailability and toxicity of polycyclic aromatic hydrocarbons toHyalella aztecain sediments from manufactured-gas plant sites
Authors: Kreitinger Joseph P. , Neuhauser Edward F. , Doherty Francis G. , Hawthorne Steven B.
Published: May 2007

The toxicity of polycyclic aromatic hydrocarbons (PAHs) to Hyalella azteca, was measured in 34 sediment samples collected from four manufactured-gas plant (MGP) sites ranging in total PAH16 (sum of 16 U.S. Environmental Protection Agency priority pollutant PAHs) concentrations from 4 to 5,700 mg/kg, total organic carbon content from 0.6 to 11%, and soot carbon from 0.2 to 5.1%. The survival and growth of H. azteca in 28-d bioassays were unrelated to total PAH concentration, with 100% survival in one sediment having 1,730 mg/kg total PAH16, whereas no survival was observed in sediment samples with concentrations as low as 54 mg/kg total PAH16. Twenty-five of the 34 sediment samples exceeded the probable effects concentration screening value of 22.8 mg/kg total PAH13 (sum of 13 PAHs) and equilibrium partitioning sediment benchmarks for PAH mixtures (on the basis of the measurement of 18 parent PAHs and 16 groups of alkylated PAHs, [PAH34]); yet, 19 (76%) of the 25 samples predicted to be toxic were not toxic to H. azteca. However, the toxicity of PAHs to H. azteca was accurately predicted when either the rapidly released concentrations as determined by mild supercritical fluid extraction (SFE) or the pore-water concentrations were used to establish the bioavailability of PAHs. These results demonstrate that the PAHs present in many sediments collected from MGP sites have low bioavailability and that both the measurement of the rapidly released PAH concentrations with mild SFE and the dissolved pore-water concentrations of PAHs are useful tools for estimating chronic toxicity to H. azteca.
Influence of isolation on the recovery of pond mesocosms from the application of an insecticide. I. Study design and planktonic community responses
Authors: Hanson Mark L. , Graham David W. , Babin Emmanuelle , Azam Didier , Coutellec Marie-Agnes , Knapp Charles W. , Lagadic Laurent , Caquet Thierry
Published: May 2007

The influence of relative isolation on the ecological recovery of freshwater outdoor mesocosm communities after an acute toxic stress was assessed in a 14-month-long study. A single concentration of deltamethrin was applied to 8 out of 16 outdoor 9-m3 mesocosms to create a rapid decrease of the abundance of arthropods. To discriminate between external and internal recovery mechanisms, four treated and four untreated (control) mesocosms were covered with 1-mm mesh screen lids. The dynamics of planktonic communities were monitored in the four types of ponds. The abundance of many phytoplankton taxa increased after deltamethrin addition, but the magnitude of most increases was relatively small, probably due to low nutrient availability and the survival of rotifers. The greatest impact on zooplankton was seen in Daphniidae and, to a lesser extent, calanoid copepods. Recovery (defined as when statistical analysis failed to detect a difference in the abundance between the deltamethrin-treated ponds and corresponding control ponds for two consecutive sampling dates) of Daphniidae was observed in the water column 105 and 77 d after deltamethrin addition in open and covered mesocosms, respectively, and <42 d for both open and covered ponds at the surface of the sediments. Rotifers did not proliferate, probably because of the survival of predators (e.g., cyclopoid copepods). These results confirm that the recovery of planktonic communities after exposure to a strong temporary chemical stress mostly depends upon internal mechanisms (except for larvae of the insect Chaoborus sp.) and that recovery dynamics are controlled by biotic factors, such as the presence of dormant forms and selective survival of predators.
Influence of isolation on the recovery of pond mesocosms from the application of an insecticide. II. Benthic macroinvertebrate responses
Authors: Caquet Thierry , Hanson Mark L. , Roucaute Marc , Graham David W. , Lagadic Laurent
Published: May 2007

The immediate response and recovery of the macrobenthic communities of nonisolated and isolated freshwater outdoor 9 m3 mesocosms following an acute stress caused by the addition of deltamethrin were studied over a 14-month period. To discriminate between internal and external recovery mechanisms, half of the treated ponds were covered by 1-mm mesh lids that restricted aerial recolonization. Both structural (abundance of the different taxonomic groups) and functional (litter breakdown) parameters were monitored. Insects were broadly reduced in numbers by deltamethrin addition. In general, noninsect groups were not affected or increased in abundance in deltamethrin-treated ponds, probably because of relative insensitivity to deltamethrin, reduced predation, and lower competition for food. No major change in litter breakdown rates were seen, probably because of functional redundancy among the macrobenthic community. Chironominae larvae recovered in open, treated mesocosms 62 d after deltamethrin addition and most insect groups recovered 84 d after the treatment date. However, the presence of lids significantly reduced insect recovery rate, suggesting that it largely depends on the immigration of winged forms (i.e., external recovery) from surrounding non- or less affected systems. These results indicate that the recovery time of macrobenthic communities in an affected natural pond would depend on spatial characteristics of the landscape and also the season that exposure occurs. Isolated ecosystems would display posttreatment insect recovery dynamics very different from highly connected ones, evolving toward alternate pseudoequilibrium states, possibly with lower biodiversity but with preserved functionality. Consequences for higher tier risk assessment of pesticides are discussed.
In vitro-in vivo extrapolation of quantitative hepatic biotransformation data for fish. II. Modeled effects on chemical bioaccumulation
Authors: Nichols John W. , Fitzsimmons Patrick N. , Burkhard Lawrence P.
Published: May 2007

Hypothetical in vitro biotransformation rate and affinity values for fish were extrapolated to a set of in vivo whole-body metabolism rate constants. A one-compartment model was then used to investigate potential effects of metabolism on chemical bioaccumulation as a function of octanol/water partitioning (KOW). In a second model-based effort, in vitro data were incorporated into a physiologically based toxicokinetic (PBTK) model for fish. The two models predict similar effects on bioaccumulation when calculated in vivo intrinsic clearance values (CLIN VIVO, INT are less than 50% of estimated liver blood flow (QLIVER). When CLIN VIVO, INT approaches QLIVER, the PBTK model predicts a greater effect on bioaccumulation than the one-compartment model. This result is attributed to the structure of the PBTK model, which provides for first-pass clearance of chemicals taken up from food. Uncertainties inherent to in vitro-in vivo extrapolations of hepatic metabolism data include the effects of protein binding, inaccurate estimation of in vivo metabolism by in vitro assays, and failure to account for metabolism in other tissues. Model-based predictions of bioaccumulation within a natural setting also must account for possible metabolism at multiple trophic levels. The models described in this study can be used to perform in vitro–in vivo metabolism comparisons with fish, estimate in vitro biotransformation parameters on the basis of measured chemical residues in field-collected animals, and calculate the level of in vitro metabolic activity required to limit bioaccumulation of all compounds to a specified value.
Toxicity of substituted anilines toPseudokirchneriella subcapitataand quantitative structure-activity relationship analysis for polar narcotics
Authors: Chen Chung-Yuan , Ko Chia-Wen , Lee PO-I
Published: May 2007

This study evaluated the toxic effects of substituted anilines on Pseudokirchneriella subcapitata with the use of a closed algal toxicity testing technique with no headspace. Two response endpoints (i.e., dissolved oxygen production [DO] and algal growth rate) were used to evaluate the toxicity of anilines. Both DO and growth rate endpoints revealed similar sensitivity to the effects of anilines. However, trichloroanilines showed stronger inhibitory effects on microalgal photosynthetic reactions than that on algal growth. For various aquatic organisms, the relative sensitivity relationship for anilines is Daphnia magna > luminescent bacteria (Microtox) ≥ Pocelia reticulata ≥ Pseudokirchneriella subcapitata ≥ fathead minnow > Tetrahymena pyriformis. The susceptibility of P. subcapitata to anilines is similar to fish, but P. subcapitata is apparently less sensitive than the water flea. The lack of correlation between the toxicity revealed by different aquatic organisms (microalgae, D. magna, luminescent bacteria, and P. reticulata) suggests that anilines might have different metabolic routes in these organisms. Both hydrogen bonding donor capacity (the lowest unoccupied molecular orbital energy, Elumo) and hydrophobicity (1-octanol:water partition coefficient, KOW) were found to provide satisfactory descriptions for the toxicity of polar narcotics (substituted anilines and chlorophenols). Quantitative structure-activity relationships (QSARs) based on Elumo, log KOW, or both values were established with r2 values varying from 0.75 to 0.92. The predictive power for the QSAR models were found to be satisfactory through leave-one-out cross-validation. Such relationships could provide useful information for the estimation of toxicity for other polar narcotic compounds.
Uptake, accumulation, phytotoxicity, and removal of 2,4-dichlorophenol in willow trees
Authors: Ucisika Ahmed Suheyl , Trapp Stefan , Kusk Kresten Ole
Published: May 2007

The relation between uptake, accumulation, toxicity and removal of 2,4-dichlorophenol (2,4-DCP) in willow trees (Salix viminalis) and the feasibility of implementing phytoremediation as a treatment method for 2,4-DCP contamination in wastewater and soil were investigated. Willows were exposed to various 2,4-DCP concentrations between 5 and 150 mg/L in hydroponic solution and between 9.1 and 44.4 mg/L in sand under constant illumination. The transpiration of the trees was used to determine toxic effects. In both hydroponic solution and sand, severe inhibition of transpiration started approximately at 2,4-DCP concentrations of 20 mg/L. Accumulation in willows was increased with higher concentrations. In surviving trees, the loss of chemical from the system was above 65%. In experiments performed without trees, the mass loss of 2,4-DCP was only 8 to 14%. For trees with detached roots, there was a significantly higher amount of 2,4-DCP remaining in the nutrient solution at the end of the experiment compared to experiments with the intact trees. The results indicate that degradation in the root zone, either by root cells or associated microorganisms, is the main reason for the removal of 2,4-DCP from the media. Phytoremediation of 2,4-DCP with willow trees does not seem to be a remediation option because of its high toxicity to trees and the limited removal efficiency.
Bioaccumulation and biotransformation of arsenic in the Mediterranean polychaete Sabella spallanzanii experimental observations
Authors: Notti Alessandra , Fattorini Daniele , Razzetti Erika M. , Regoli Francesco
Published: May 2007

The Mediterranean fan worm Sabella spallanzanii is characterized by elevated basal levels of arsenic in branchial crowns (>1,000 μg/g) and an unusual prevalence of dimethylarsinic acid (DMA), a relatively toxic compound with a possible antipredatory role. The aim of this work was to obtain further insights on the capability of this polychaete to accumulate arsenic from different compounds and to operate biotransformation reactions. Laboratory exposures to arsenate (AsV), dimethylarsinic acid (DMA), trimethylarsine (TMA), and arsenobetaine (AsB) revealed significant differences among tissues and kind of experiments. The highest increases of arsenic content were observed in branchial crowns of organisms treated with arsenate, which can enter the cell through the phosphate carrier system; lower variations were measured with DMA and TMA, while not-significant changes of total As occurred after treatments with AsB. In body tissues, exposure to AsV, DMA, and TMA confirmed a progressively lower accumulation of total arsenic, while a marked increase was caused by AsB. Obtained results suggested that accumulated arsenic could be chemically transformed, thus explaining the elevated basal levels of DMA typical of S. spallanzanii; during all the experiments, DMA was the most accumulated molecule, suggesting that this species possesses the enzymatic pathways for methylation and demethylation reactions of inorganic and trimethylated arsenicals. Only arsenobetaine was not converted into DMA, which would confirm a microbial pathway for degradation for this molecule, particularly important in body tissues of S. spallanzanii for the presence of bacteria associated to digestive tracts. Overall, the present study suggests future investigations on the biological role of arsenic and DMA in S. spallanzanii as a potential adaptive mechanism against predation in more vulnerable tissues.
Tracing salmon-derived nutrients and contaminants in freshwater food webs across a pronounced spawner density gradient
Authors: Gregory-Eaves Irene , Demers Marc J. , Kimpe Lynda , Krümmel Eva M. , Macdonald Robie W. , Finney Bruce P. , Blais Jules M.
Published: May 2007

Many have demonstrated that anadromous Pacific salmon are significant vectors of nutrients from the ocean to freshwaters. Recently, however, it has been recognized that salmon spawners also input significant quantities of contaminants. The objectives of this paper are to delineate the extent to which salmon-derived nutrients are integrated into the freshwater food web using δ15N and δ13C and to assess the influence of the salmon pathway in the accumulation of contaminants in rainbow trout (Oncorhynchus mykiss). We found that the δ15N and δ13C of food web components were related positively and significantly to sockeye salmon (Oncorhynchus nerka) spawner density. Contaminant concentrations in rainbow trout also positively and significantly were related to sockeye salmon spawner density. These data suggest that the anadromous salmon nutrient and contaminant pathways are related and significantly impact the contaminant burden of resident fish.
Ketoconazole in the fathead minnow (Pimephales promelas): Reproductive toxicity and biological compensation
Authors: Ankley Gerald T. , Jensen Kathleen M. , Kahl Michael D. , Makynen Elizabeth A. , Blake Lindsey S. , Greene Katie J. , Johnson Rodney D. , Villeneuve Daniel L.
Published: May 2007

Ketoconazole (KTC) is a model pharmaceutical representing imidazole and triazole pesticides, which inhibit fungal growth through blocking a cytochrome P450 (CYP)-mediated step in ergosterol biosynthesis. Several of these fungicides have been shown to be reversible inhibitors of CYPs in vertebrates (primarily mammals), including CYP isoforms involved in the pathway that converts cholesterol to active sex steroids. In these studies, we assessed the effects of KTC on aspects of steroidogenesis and reproductive function in the fathead minnow (Pimephales promelas). Exposure of spawning adults to the fungicide for 21 d significantly decreased egg production at a water concentration as low as 25 μg/L. Despite evidence of reduced ex vivo testosterone production by gonads from KTC-exposed fathead minnows, circulating plasma concentrations of sex steroids (testosterone, 17β-estradiol) were not affected. Exposure to KTC caused an increase in the gonadosomatic index in both sexes and, in males, the fungicide caused a marked proliferation of interstitial (Leydig) cells. In addition, mRNA transcripts for two key steroidogenic enzymes, cytochrome P450 side-chain cleavage (CYP11A) and cytochrome P450 c17α hydroxylase/17,20 lyase (CYP17), were elevated by exposure to KTC. Both the changes in transcript levels and proliferation of gonad tissue represent potential adaptive or compensatory responses to impaired steroidogenic capacity. Overall our data indicate that, although KTC does adversely affect steroidogenesis and reproduction in the fathead minnow, the fish can compensate to some degree to mitigate effects of the fungicide. This has important implications for the interpretation of data from tests with endocrine-active chemicals.
Organochlorine pesticides in seafood products from Southern China and health risk assessment
Authors: Guo Jian-Yang , Zeng Eddy Y. , Wu Feng-Chang , Meng Xiang-Zhou , Mai Bi-Xian , Luo Xiao-Jun
Published: May 2007

Seafood consumption is an important route of human exposure to organic contaminants. Residual levels of organochlorine pesticides (OCPs), including DDTs, hexachlorocyclohexanes (HCHs), heptachlor, aldrin, α-endosulfan, β-endosulfan, dieldrin, endrin, endrin aldehyde, endrin ketone, methoxychlor, endosulfan sulfate, and heptachlor epoxide, were determined in a wide variety of seafood products collected from 11 coastal cities in southern China in June and October 2005. The results indicated that OCPs were predominated by DDTs and HCHs. The concentrations of other OCP components generally were low and were detectable in a small number of seafood samples only, probably reflective of the generally low levels of these OCPs in the study region and low bioaccumulation potentials in the species under investigation. Risk assessment against various standards clearly showed that seafood products were highly contaminated by DDTs and may pose health threat to local residents and the consumers all over the world. Furthermore, other OCP components, such as dieldrin and heptachlor, also impose lifetime cancer risk, especially to residents of coastal regions who often consume more seafood than those living inland. Therefore, continual monitoring of OCPs in various environment compartments, including biota and abiota, urgently is needed to mitigate effectively the impact of OCPs, particularly DDTs, on human health and the ecological environment.
Lethal and sublethal effects of chronic cadmium exposure on northern leopard frog (Rana pipiens) tadpoles
Authors: Gross Jackson A. , Chen Te-Hao , Karasov William H.
Published: May 2007

Data on the chronic effects of cadmium on amphibians are lacking in spite of widespread anthropogenic contamination of terrestrial and aquatic systems. We exposed embryos and tadpoles of northern leopard frogs (Rana pipiens) to Cd (control, 0.25, 5.0, and 20.0 μg/L as CdCl2, nominal concentrations) in a static renewal system from embryonic stages to complete tail resorption. Survival of embryos (Gosner stage [GS] 17–25) was greater than 97% in all treatments. Tadpole survival was negatively correlated with dose and was significantly reduced in the 5.0 and 20.0 μg/L treatments compared with controls. Tadpole survival was greater than 80% through GS 42, forelimb emergence, for all other treatments. Tadpoles exposed to 0.25 and 5.0 μg/L exhibited increased growth by week 11; tadpoles exposed to 5.0 μg/L were significantly younger at forelimb emergence. Whole-tadpole body burdens of Cd were positively correlated with increasing Cd treatments. Cadmium was shown to alter growth and development in a native amphibian species at ecologically relevant concentrations. The existing chronic water quality criterion for Cd appears to be protective of amphibians. However, additional studies with other chemicals are needed to further explore the potential for adverse effects of contaminants on the complex life cycle of amphibians.
Leaching and aging decrease nickel toxicity to soil microbial processes in soils freshly spiked with nickel chloride
Authors: Oorts Koen , Ghesquiere Uldeen , Smolders Erik
Published: May 2007

Nickel is a trace metal that exhibits pronounced long-term immobilization reactions in soil. It is unknown if the slowly decreasing solubility of Ni in soil on aging correlates with decreased toxicity to soil biota. Three uncontaminated soils (pH 4.5–7.6) were contaminated with NiCl2 and experimentally leached or incubated outdoors with free drainage for up to 15 months. Nickel toxicity was measured for three microbial processes (potential nitrification rate, glucose-induced respiration, and C mineralization of maize residue). Results for leached and aged samples were compared with results for these soils tested immediately after spiking. Experimental leaching increased Ni ED50s (Ni dose to inhibit process by 50%) with a median factor of 2.0, whereas Ni ED50s in soils aged 15 months were a factor 1 to 23 (median, 4.6) larger compared to freshly spiked soils. Changes in soil Ni toxicity on aging generally were largest in the soil with the highest pH, consistent with the largest relative decreases of soil solution Ni concentration or predicted Ni2+ activity. Soil solution Ni concentrations explained part, but not all, of the reduction in Ni toxicity. The predicted soil solution Ni2+ activity also did not fully explain the reduced toxicity, which was ascribed to the variable concentrations of ions competing with Ni2+ at biological membranes (e.g., H+, Mg2+, or Ca2+) among treatments. It is concluded that testing Ni toxicity to soil microbial processes immediately after spiking soils in the laboratory overestimates Ni toxicity compared to aged soils. Soil solution composition in freshly spiked soils clearly is different from that in leached or aged soils; therefore, soil spiked with metal salts should be leached before toxicity tests begin.
Tissue Doppler imaging for the detection and quantitation of myocardial dysfunction in patients with type 2 diabetes mellitus
Authors: Von Bibra Helene , Thrainsdottir Inga S , Hansen Alexander , Dounis Vasilios , Malmberg Klas , Rydén Lars
Published: May 2007

The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients.

Aims This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients.

Methods Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va).

Results Compared to controls, diabetic patients had compromised Ve at rest (8.5. ± 1.7 vs. 9.6 ± 1.9 cm/sec, p<0.02), as did the subgroups without coronary artery disease (9.3 ± 1.7 vs. 10.7 ± 1.5 cm/sec, p<0.05). Dobutamine stress resulted in lower Vs (10.7 ± 2.7 vs. 13.6 ± 3.4 cm/sec, p<0.05) and Ve (10.0 ± 2.1 vs. 13.1 ± 3.8 cm/sec, p<0.05) in the diabetic patients, demonstrating an impaired increase of Vs, Vd and Va (p<0.05, p<0.0003 and p<0.03, respectively). An inverse correlation was observed between Ve and age in both control and diabetic individuals. Thus, abnormal values were defined in relation to age.

Conclusions Diastolic and systolic myocardial dysfunction in patients with type 2 diabetes may be identified by quantitative tissue Doppler imaging before the onset of clinical signs of heart failure and before the appearance of traditional echocardiographic indices of systolic myocardial dysfunction.
Effect of rosiglitazone treatment on circulating vascular and inflammatory markers in insulin-resistant subjects
Authors: Chu James W , Abbasi Fahim , Lamendola Cynthia , McLaughlin Tracey , Reaven Gerald M , Tsao Philip S
Published: May 2007

Thiazolidinedione (TZD) compounds enhance insulin sensitivity and attenuate inflammation. The effect of the TZD compound, rosiglitazone (RSG) on both actions was evaluated in two groups of insulin-resistant subjects with minimal elevations of fasting plasma glucose (PG) concentration: group A (n=15, PG < 7.0 mmol/L) and group B (n=14, PG 7.0–8.3 mmol/L). Insulin action, quantified by the insulin suppression test, improved after three months of treatment in both groups, and concentrations of C-reactive protein, plasminogen activator inhibitor-1 and E-selectin all fell. Significant decreases in L-selectin and P-selectin were confined to group B, and concentrations of interleukin-6, intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1 did not fall in either group.

Significant relationships were not discerned between enhanced insulin sensitivity and related variables and decreases in inflammatory/vascular markers, suggesting that RSG-induced changes in the latter variables in insulin-resistant individuals might be at least partly independent of the effects of the drug on insulin action.
Contrasting clinical and cardiovascular risk status between early and later onset type 2 diabetes
Authors: Hatunic Mensud , Burns Nicole , Finucane Francis , Mannion Cynthia , Nolan John J
Published: May 2007

The prevalence of type 2 diabetes (T2DM) is increasing rapidly and the age of presentation is falling. These changes are likely to be linked to the current obesity epidemic. Our objective was to compare the characteristics of younger patients with T2DM (diagnosed at age < 40 years) with those of older patients (diagnosed at age 50–70 years).

We identified 149 younger patients with T2DM, from our diabetes clinic database, and compared them with 217 older T2DM patients randomly identified from the same database.

Younger patients with T2DM were more obese, more hypertriglyceridaemic, with lower high-density lipoprotein (HDL) cholesterol, higher total cholesterol/HDL ratio and worse initial and ongoing glycaemic control than older patients from the same clinic. Additional cardiovascular risk factors are associated with T2DM in the young. Treatment should be aimed at early modification of lifestyle and other forms of therapy to avoid long-term complications.
Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes
Authors: Anderson Richard A , Ellis Gethin R , Evans L. Marc , Morris Keith , Chirkov Yuri Y , Horowitz John D , Jackson Simon K , Rees Alan , Lewis Malcolm J , Frenneaux Michael P
Published: May 2007

Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function.

Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5′-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery.

Results are expressed as (mean±SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86±1.1 Ohms vs. 10.76±1.1 Ohms, p<0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1±5.9% and 50.3±7.7% in healthy controls compared to 15.4±7% and 19.5±8.2% in T2DM (p<0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance.

In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.
The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor
Authors: Espinosa-Larrañaga Francisco , Vejar-Jalaf Margarita , Medina-Santillán Roberto
Published: May 2007

In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, US, on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C.

The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease.

This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting.
Inflammation, thrombosis and acute coronary syndromes
Authors: Carter Angela M
Published: May 2007

Inflammation plays a central role in the pathogenesis of acute coronary syndromes, the prevalence of which is increased in individuals with diabetes. Monocytes and macrophages, T cells and mast cells contribute to the initiation, development and rupture of atherosclerotic plaques by synthesising a variety of pro-inflammatory cytokines, including interleukin 1β, interleukin 6 and tumour necrosis factor a. Cytokines upregulate endothelial cell adhesion molecules, recruit leukocytes and induce smooth muscle cell migration and proliferation. Cytokines act systemically to initiate the acute phase response, up-regulating proteins involved in inflammation and haemostasis and resulting in a pro-inflammatory and pro-thrombotic state. Expression of tissue factor by inflammatory cells potently induces thrombus formation upon plaque rupture, leading to acute coronary syndromes. Inflammatory biomarkers, including C-reactive protein, complement proteins, interleukin 6 and white blood cell count, predict development of acute coronary syndromes. C-reactive protein has been widely studied and consistently predicts future acute coronary syndrome events.
The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes
Authors: Collet Jean-Philippe , Montalescot Gilles
Published: May 2007

Diabetes mellitus (DM) remains an important predictor for mortality in patients with ST-segment Elevation Myocardial Infarction (STEMI) although the use of reperfusion therapy has resulted in a considerable improvement of survival. Of importance, newly diagnosed diabetic patients and those with fasting glycaemia in the diabetes range have even worse outcomes compared to patients with known diabetes. Overall, 50% of all patients presenting with STEMI have abnormal glucose metabolism of which fewer than 50% are known diabetics. Obviously, the efficacy of reperfusion therapy in reopening the occluded artery is similar in STEMI patients with or without impaired fasting glycaemia, while the pre-existing decreased myocardial perfusion in STEMI patients with impaired fasting glycaemia persists after successful epicardial revascularisation.

There is no doubt that improving microvascular perfusion within the ischaemic myocardium remains the ultimate goal of managing STEMI patients with impaired glucose metabolism. Identification of defective myocardial perfusion together with an aggressive antithrombotic regimen, reduction of the inflammatory response of the ischaemic myocardium and improvement of glycaemia control represent promising therapeutic approaches that deserve additional specific clinical investigations. This review examines all these important issues.
Management of patients with type 2 diabetes after acute coronary syndromes
Authors: Bartnik Malgorzata , Malmberg Klas , Rydén Lars
Published: May 2007

Acute coronary syndromes are associated with a high risk for subsequent major cardiovascular events and with a risk for mortality that remains substantially increased for many months following the acute phase. Patients with type 2 diabetes mellitus are especially vulnerable and encounter excessive long-term mortality. Effective management of patients with type 2 diabetes following acute coronary syndromes requires aggressive multidisciplinary efforts for reduction of several risk factors, including meticulous control of blood glucose. The evidence for different medication and treatment strategies capable of improving the outcomes is reviewed and the currently available recommendations are summarised.
Prevalence of metabolic syndrome in young patients with acute MI: does the Framingham Risk Score underestimate cardiovascular risk in this population?
Authors: Zarich Stuart , Luciano Carlo , Hulford Jackie , Abdullah Arif
Published: May 2007

To assess the prevalence of metabolic syndrome (MS) and estimates of global risk by Framingham Risk Score in young subjects with acute myocardial infarction (MI), we assessed metabolic parameters and global risk assessment in 165 consecutive subjects who presented with myocardial infarction prior to 45 years of age. Nearly 80% of subjects were overweight or obese and at least one cardiovascular risk factor was present in 96% of patients. MS with or without overt diabetes was present in nearly two thirds of subjects. Excluding subjects with diabetes, the mean 10-year Framingham Risk Score estimate in the total cohort was 9. 3%, with only 17. 1% of subjects having a 10-year risk greater than 20%. Only 28% of subjects with MS had a Framingham Risk Score greater than 20%. Although MS is present in nearly two thirds of young patients with premature myocardial infarction, the Framingham Risk Score appears to underestimate global cardiovascular risk in this population.
New perspectives on the management of diabetic peripheral neuropathic pain
Authors: Jensen Troels S , Backonja Misha-Miroslav , Jiménez Sergio Hernández , Tesfaye Solomon , Valensi Paul , Ziegler Dan
Published: May 2007

Peripheral neuropathy affects about 30% of people with diabetes mellitus. Between 16% and 26% of diabetes patients experience chronic pain. This may be referred to as diabetic neuropathic pain (DNP) or diabetic peripheral neuropathic pain (DPNP). Minimum requirements for diagnosis of DPNP should include assessment of pain and symptoms and neurological examination, with the accent on sensory examination. Given that depression and other co-morbidities are commonly associated with this condition, a broad approach to management is essential. Lifestyle intervention and optimisation of glycaemic control are recommended as initial steps in management.

An evidence-based treatment algorithm for DPNP has been proposed, recommending initial use of either a tri-cyclic antidepressant, selective serotonin noradrenaline re-uptake inhibitor or alpha-2-delta agonist, depending on patient co-morbidities and contra-indications. Addition of an opioid agonist may be required in the event of inadequate pain control. Irrespective of which treatment is offered, only about one third of patients are likely to achieve more than 50% pain relief. Further research to improve the diagnosis and management of DPNP is needed.