bluuebunny/crossref_metadata_2025 huggingface dataset:
New organochlorine contaminants and metabolites in plasma and eggs of glaucous gulls (Larus hyperboreus) from the Norwegian Arctic
Authors: Verreault Jonathan , Letcher Robert J. , Muir Derek C.G. , Chu Shaogang , Gebbink Wouter A. , Gabrielsen Geir W.
Published: October 2005

The present study investigated new or lesser-studied and legacy organochlorine (OC) contaminants and metabolites in plasma and eggs of glaucous gulls (Larus hyperboreus) collected from major breeding colonies on Bear Island in the Norwegian Arctic. Hexachlorobutadiene was below the method limit of detection (<0.07 ng/g lipid wt) in all samples. The sum (sum) of 20 chlorobornane congener concentrations ranged between 294 and 986 ng/g lipid weight and 104 and 1,121 ng/g lipid weight in plasma and eggs, respectively, whereas those of ∑20polychlorinated naphthalene ranged between 1.34 and 126 ng/g lipid weight in plasma and 1.82 and 162 ng/g lipid weight in eggs. Bis(4-chlorophenyl) sulfone concentrations ranged between 5.24 and 143 ng/g lipid weight plasma, which is the first report of this contaminant in arctic biota north of Sweden. Based on 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs), partial dioxin-like toxicity varied between 3.04 and 20.8 ng TEQ/g lipid weight in plasma and 0.94 and 46.5 ng TEQ/g lipid weight in eggs, and largely was due to concentrations of non-ortho polychlorinated biphenyls (PCBs), with a very minor contribution from mono-ortho PCBs and polychlorinated naphthalenes. The major aryl sulfone metabolite in plasma was an unidentified hexachlorinated MeSO2-PCB congener (range: 13.5–551 ng/g lipid wt), whereas the pentachlorinated congeners 3′- and 4′-MeSO2-CB101 (range: 4.49–38.1 ng/g lipid wt) dominated in eggs. The predominant halogenated phenolic compound (HPC) in plasma was consistently the PCB metabolite 4-OH-CB187 (range: 0.29–17.5 ng/g wet wt), whereas in eggs, detectable HPCs were at very low and transient concentrations. As part of a complex profile of contaminant exposure, these chemical classes and metabolites may be contributing factors to enhance physiological stress in breeding glaucous gulls.
Effect-directed analysis of mutagens and ethoxyresorufin-O-deethylase inducers in aquatic sediments
Authors: Brack Werner , Schirmer Kristin , Erdinger Lothar , Hollert Henner
Published: October 2005

Sediment extracts from a creek in the Neckar river basin (Germany), which received the discharge of treated hospital wastewater, were found to exhibit strong aromatic hydrocarbon (Ah) receptor-mediated effects in a rainbow trout liver cell line (RTL-W1) as well as high mutagenicity in the Salmonella/microsome assay after fractionation. The crude extract did not exhibit a clear mutagenic response. Apparently, cleanup or fractionation before mutagenicity testing is necessary to minimize the risk of false-negative results. Effect-directed fractionation and analysis were applied to characterize and identify the toxicants that cause these effects. Major ethoxyresorufin-O-deethylase induction potency and mutagenicity were detected in different polyaromatic fractions, indicating different sets of toxicants that induce metabolic activation and mutagenicity. Dioxin-like halogenated aromatic hydrocarbons, including polychlorinated biphenyls, naphthalenes, dibenzo-p-dioxins and furans, and priority polycyclic aromatic hydrocarbons, contributed to Ah receptor-mediated activity only to a minor extent. Benzo[a]pyrene, benzo[a]fluoranthene, and perylene could be confirmed as important contributors to mutagenicity. The nonpriority pollutants 11H-indeno[2,1,7-cde]pyrene, a methylbenzo[e]pyrene, and a methylperylene were tentatively identified as major components, representing 82% of the peak area of a highly mutagenic fraction of the sediment extract. This suggests that hazard and risk assessment of complex environmental mixtures should make increasing attempts to identify and consider hazardous key pollutants rather than focusing on a priori-selected key pollutants alone.
Metal and oxygen uptake in the green mussel Perna viridis under different metabolic conditions
Authors: Wang Jingfeng , Chuang Chia-Ying , Wang Wen-Xiong
Published: October 2005

Coupled respirometric and radiotracer techniques were applied to simultaneously measure the rates of oxygen and metal uptake in the green mussel Perna viridis. This was performed under different metabolic conditions by varying the ambient oxygen partial pressure (Po2), temperature, air exposure, and body size. When the mussels were tested under different hypoxic and anoxic conditions, Cd and Zn uptake decreased with decreasing Po2, accompanied by a decrease in the ventilation activity of mussels. Significant reduction in metal uptake was observed at a Po2 level of 3 kPa. Under anoxic conditions, the uptake of Cd and Zn was 1.6 to 2.7 times and 2.8 times, respectively, lower than those measured under normoxia. In contrast, both the absorption efficiencies of Cd and Zn and the oxygen extraction efficiency increased significantly with decreasing Po2. There were significant correlations between the rates of Cd/Zn and O2 uptake by the mussels when quantified under various Po2 levels. The uptake of Cd and Zn was temperature dependent and increased with temperature over a range of 15 to 30°C. Significant correlations between the rates of Cd/Zn and O2 uptake were also found in the temperature experiments. With reimmersion of mussels after aerial exposure, the mussels experienced an apparent O2 debt. Metal uptake also increased within the first 15 min followed by gradual recovery to the control levels. Similarly, the quantified uptake rates of Zn were significantly correlated with the O2 uptake in experiments with different sizes of mussels. These results strongly suggest that Cd and Zn uptake are coupled with oxygen uptake in the mussels; thus, physiological processes need to be considered in studying metal accumulation.
Comparison of different androgen bioassays in the screening for environmental (anti)androgenic activity
Authors: Christiaens Valerie , Berckmans Pascale , Haelens Annemie , Witters Hilda , Claessens Frank
Published: October 2005

Endocrine disruptors pose a growing threat to human and wildlife health. Validated test systems are required to study the mechanisms by which chemicals may interfere with the endocrine system. In order to identify compounds with (anti)androgenic activity, we used several in vitro bioassays, based on different androgen receptor (AR) functions, including AR transactivation and interaction between the amino-terminal domain and the ligand-binding domain. The AR activity assay, based on activation of the transcription of an androgen-responsive reporter gene in the presence of androgen, proved to excel in terms of high fold induction range and low minimal detection limit. The EC50 value, defined as the concentration that leads to half the maximal response and reflecting the potency of the synthetic androgen R1881 (methyltrienolone), was found to be 250 pM, consistent with the high affinity of this ligand to the human AR. A number of environmental samples were tested in the bioassay. The bioassay also could be used to detect antiandrogenic activity, because known AR-antagonists were able to inhibit R1881-mediated transactivation.
Potential ecotoxic effects of polychlorinated biphenyls on Xenopus laevis
Authors: Qin Zhan-Fen , Zhou Jing-Ming , Cong Lin , Xu Xiao-Bai
Published: October 2005

We examined potential ecotoxic effects of polychlorinated biphenyl (PCB)3, PCB5, Aroclor 1254, and Aroclor 1242 on Xenopus laevis. Tadpoles were exposed to PCBs from stage 46/47 (system of Nieuwkoop and Faber) to the completion of metamorphosis. We demonstrated, to our knowledge for the first time, forelimb malformations caused by PCBs (malformation rate, >70%). The malformed forelimbs were fixed in the adduction-backward rotation position and could not move. Therefore, malformed male frogs were destined to have no offspring, because they could not grasp the females with their forelimbs to mate. Alcian blue-alizarin red double-staining indicated that the forelimb malformation resulted from the shoulder abnormality. Compared with the normal shoulder joint, the proximal humerus with the humerus inter-rotated 90° in the abnormal shoulder joint. Moreover, testes from more than a third of male frogs with exposed to PCBs exhibited feminization to different degrees at gross morphology and histology, with fewer or abnormal spermatogonia and oocytes. Gonadal abnormalities would lead directly to reproductive dysfunction and population decline. These results suggest that PCBs have potentially ecotoxic effects on amphibian populations. We infer that PCBs could play roles in amphibian malformations and population declines, at least at sites that are polluted heavily with PCBs.
Peptide Nucleic Acids (PNAs), A Chemical Overview
Authors: Porcheddu Andrea , Giacomelli Giampaolo
Published: October 2005

Peptide nucleic acid (PNA) is a nucleic acid analogue and a fully synthetic DNA/RNA-recognising ligand with a neutral peptide-like backbone. In spite of the large change on the backbone structure, PNA molecules bind strongly to complementary DNA and RNA sequences. Originally conceived as ligand for the recognition of double stranded DNA, the unique physico-chemical properties of PNAs have led to the development of a variety of research and diagnostic assays. The extraordinary properties of PNA may advance routine clinical tests and environmental analyses that will utilise the PNA technology. PNAs may also have an impact on in situ hybridisation, cytogenetics and industrial microbiology. This paper presents some recent achievements on peptide nucleic acids and discusses, from the viewpoint of literature, what the potential is and what the limitations of such compounds are. This review, which is not intended to be exhaustive, is mostly aimed at the current progress in PNA chemistry, structure, and hybridisation, highlighting some applications too.
Naturally-Occurring Xanthones: Recent Developments
Authors: Vieira L. M.M. , Kijjoa A.
Published: October 2005

A literature survey covering the report of naturally occurring xanthones from January 2000 to December 2004, with 219 references, is presented in this review. Among 515 xanthones reported in this period, 278 were new natural xanthones. These xanthones have been identified from 20 families of higher plants (122 species in 44 genera), fungi (19 species) and lichens (3 species). The structural formulas of 368 identified xanthones, their distribution and a brief mention of their biological properties are also included.
Xanthone Derivatives: New Insights in Biological Activities
Authors: Pinto M. M.M. , Sousa M. E. , Nascimento M. S.J.
Published: October 2005

Xanthones or 9H-xanthen-9-ones (dibenzo-γ-pirone) comprise an important class of oxygenated heterocycles whose role is well-known in Medicinal Chemistry. The biological activities of this class of compounds are associated with their tricyclic scaffold but vary depending on the nature and/or position of the different substituents. In this review, an array of biological/pharmacological effects is presented for both natural and synthetic xanthone derivatives, with an emphasis on some significant studies on structure-activity relationships. The antitumor activity of some xanthones as well as the related targets, particularly PKC modulation studies, is also discussed in detail. Examples of the "hit" compounds involved in cancer therapy, namely DMXAA, psorospermin, mangiferin, norathyriol, mangostins, and AH6809, a prostanoid receptor antagonist, are also mentioned. Finally, a historical perspective of these xanthonic derivatives, their relevance as therapeutic agents and/or their uses as pharmacological tools and as extract components in folk medicine are also highlighted.
Structure Elucidation of Xanthone Derivatives: Studies of Nuclear Magnetic Resonance Spectroscopy
Authors: Silva A. M.S. , Pinto D. C.G.A.
Published: October 2005

1H and 13 C NMR spectra remain the first tool used by chemists to perform the structure elucidation of their products on a routine basis. It is common to provide NMR data on both proton and carbon spectra based on one-dimensional experiments, but often only proton resonances are assigned. The increasing complexity of natural compounds and their synthetic related derivatives imply the use of some more recent 1D and 2D NMR techniques. The purpose of this review is to describe the main NMR features of the most common and important classes of xanthones and also to discuss the application of several 1D and 2D NMR techniques in the structure elucidation of these compounds. A brief discussion of these NMR techniques from the point of view of structure elucidation of organic compounds will also be considered. The calculated NMR chemical shifts in the structure elucidation of xanthones and the use of NMR to study their mode of action in biological activities will be also described.
Xanthones-A Structural Perspective
Authors: Gales L. , Damas A. M.
Published: October 2005

Xanthones, synthesized or isolated from a natural source, display a wide range of biological and pharmacological activities. In a few cases, their chemical characterization has involved the structure elucidation by single crystal X-ray diffraction. The purpose of this review is to assess in detail this three-dimensional structural data, and thus contribute to a better understanding of the molecular mechanisms involved in the different biological activities presented by xanthones.
Factor structure of the Buss‐Perry aggression questionnaire in different samples and languages
Authors: Vigil‐Colet Andreu , Lorenzo‐Seva Urbano , Codorniu‐Raga Maria J. , Morales Fabia
Published: October 2005

This study aims to analyze the factorial structure of the aggression questionnaire developed by Buss and Perry [1992]. Many studies of different adaptations of the questionnaire have shown its lack of fit to the 4–factor structure proposed by Buss and Perry because of the functioning of certain items. The present study applies consensus oblimin rotation to five of these studies in an attempt to assess the degree of congruence within these factorial structures and, if necessary, to remove the problematical items. This method simultaneously rotates the loading matrices obtained in several studies to achieve a mixture of simplicity and optimal agreement between them. The factorial structures reported by Buss and Perry [1992] in English, Nakano [2001] in Japanese, Ramirez et al. [2001] in Japanese and Spanish, and Garcia‐León et al. [2002] in Spanish, were used. Results show that the congruence between the different factorial solutions is considerable, although certain items show low congruence values. The result for these items was taken into account, and a reduced version was proposed that does not include them. The results show that this reduced version of the test could be congruent among samples and languages. Aggr. Behav. 00:1–8, 2005. © 2005 Wiley‐Liss, Inc.
Cortical complexity in cetacean brains
Authors: Hof Patrick R. , Chanis Rebecca , Marino Lori
Published: October 2005

Cetaceans (dolphins, whales, and porpoises) have a long, dramatically divergent evolutionary history compared with terrestrial mammals. Throughout their 55–60 million years of evolution, cetaceans acquired a compelling set of characteristics that include echolocation ability (in odontocetes), complex auditory and communicative capacities, and complex social organization. Moreover, although cetaceans have not shared a common ancestor with primates for over 90 million years, they possess a set of cognitive attributes that are strikingly convergent with those of many primates, including great apes and humans. In contrast, cetaceans have evolved a highly unusual combination of neurobiological features different from that of primates. As such, cetacean brains offer a critical opportunity to address questions about how complex behavior can be based on very different neuroanatomical and neurobiological evolutionary products. Cetacean brains and primate brains are arguably most meaningfully conceived as alternative evolutionary routes to neurobiological and cognitive complexity. In this article, we summarize data on brain size and hemisphere surface configuration in several cetacean species and present an overview of the cytoarchitectural complexity of the cerebral cortex of the bottlenose dolphin. © 2005 Wiley‐Liss, Inc.
Overview of the visual system of tarsius
Authors: Collins Christine E. , Hendrickson Anita , Kaas Jon H.
Published: October 2005

Tarsiers, which are currently considered to constitute the sister group of anthropoid primates, exhibit a number of morphological specializations such as remarkably large eyes, big ears, long hind legs, and a nearly naked tail. Here we provide an overview of the current state of knowledge on the tarsier visual system and describe recent anatomical observations from our laboratory. Its large eyes notwithstanding, the most remarkable feature of the tarsier brain is the large size and distinct lamination of area V1. Based on the need of tarsier for optimal scotopic vision and acuity to detect small prey in low lighting conditions, tarsiers may have preserved a high level of visual acuity by enlarging V1 at the expense of other areas. The other classically described visual regions are present in tarsier, albeit many borders are not clearly distinct on histochemical or immunohistochemical preparations. Tarsiers also have a large number and unusual distributions of cones in the retina, with high numbers of M/L‐cones in the central retina and S‐cones surprisingly at the periphery, which may be sensitive to UV light and may be useful for prey detection. These adaptive specializations may together account for the unique nocturnal predatory requirements of tarsiers. © 2005 Wiley‐Liss, Inc.
Purinergic receptor antagonists inhibit odorant‐induced heat shock protein 25 induction in mouse olfactory epithelium
Authors: Hegg Colleen C. , Lucero Mary T.
Published: October 2005

Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE). Extracellular ATP, a signal of cellular stress, induces the expression of HSPs via purinergic receptors. In the present study, in vivo odorant exposure (heptanal or R‐carvone) led to a selective induction of HSP25 in glia‐like sustentacular cells in the Swiss Webster mouse OE, as previously shown in rats (Carr et al., 2001). Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells. ATP released by acutely injured cells could act as an early signal of cell and tissue damage, causing HSP expression and initiating a stress signaling cascade to protect against further damage. Sustentacular cells have a high capacity to detoxify xenobiotics and thereby protect the olfactory epithelium from airborne pollutants. Thus, the robust, rapid induction of HSPs in sustentacular cells may help maintain the integrity of the OE during exposure to toxicants. © 2005 Wiley‐Liss, Inc.
Astrocyte differentiation selectively upregulates CCL2/monocyte chemoattractant protein‐1 in cultured human brain‐derived progenitor cells
Authors: Lawrence Diane M.P. , Seth Pankaj , Durham Linda , Diaz Frank , Boursiquot Roosevelt , Ransohoff Richard M. , Major Eugene O.
Published: October 2005

Chemokines (chemoattractant cytokines) and their receptors are present in the brain and may play roles in both neurodevelopment and neuropathology. Increased brain levels of monocyte chemoattractant protein‐1 (MCP‐1), also known as CCL2, are found in patients with human immunodeficiency virus type 1 (HIV‐1)‐associated dementia and other acute and chronic neurologic diseases. Although the function of CCL2 in the brain is unclear, it is believed that upregulation of this chemokine during neuropathologic or neuroinflammatory conditions leads to recruitment of activated monocytes into the brain, where they differentiate into macrophages producing neurotoxic and inflammatory molecules. We recently showed that human fetal brain‐derived progenitor cells are susceptible to HIV‐1 and JC virus infection, and that differentiation toward an astrocyte phenotype increased virus production from these cells. In the current study, we found that in the absence of infection, progenitors produced moderate levels of CCL2 (5.6 ng per million cells). Astrocyte differentiation over 3 weeks increased CCL2 protein levels 30‐fold in a biphasic manner, whereas neuronal differentiation decreased production 20‐fold. Electromobility shift assays (EMSAs) demonstrated increased nuclear NF‐κB levels within 2 h of initiating astrocyte differentiation, and inhibitors of NF‐κB activation partially blocked the CCL2 increase in differentiating astrocytes. Transfection of progenitors with mutated CCL2 promoter/CAT reporter constructs showed that the distal promoter region, containing NF‐κB and NF‐I binding sites, is important for differentiation‐induced CCL2 upregulation. Together these results suggest that the transcription factor NF‐κB, and possibly NF‐I, contribute to the upregulation of CCL2 chemokine production during the differentiation of human progenitor cells toward an astrocyte phenotype. © 2005 Wiley‐Liss, Inc.
HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines
Authors: El‐Hage Nazira , Wu Guanghan , Wang Juan , Ambati Jayakrishna , Knapp Pamela E. , Reed Janelle L. , Bruce‐Keller Annadora J. , Hauser Kurt F.
Published: October 2005

Opiates exacerbate human immunodeficiency virus type 1 (HIV‐1) Tat1‐72‐induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein‐1 (MCP‐1, also known as CCL2), in particular, is potentiated by opiate–HIV Tat interactions in vitro. Although MCP‐1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP‐1 in neuro‐acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat1‐72than in vehicle‐, μ‐opioid receptor (MOR) antagonist‐, or inactive, mutant TatΔ31‐61‐treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP‐1 antibodies, or medium from MCP‐1−/−astrocytes. In the presence of morphine (time‐release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+macrophages at 7 days post‐injection. This was not seen after treatment with Tat alone, or with morphine plus inactive TatΔ31‐61or naltrexone. Glia displayed increased MOR and MCP‐1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP‐1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial‐derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate‐driven amplification/positive feedback of MCP‐1 production and inflammation. © 2005 Wiley‐Liss, Inc.
Divergent effects of oncostatin M on astroglioma cells: Influence on cell proliferation, invasion, and expression of matrix metalloproteinases
Authors: Chen Shao‐Hua , Gillespie G. Yancey , Benveniste Etty N.
Published: October 2005

Oncostatin M (OSM), a cytokine of the interleukin‐6 (IL‐6) family, can either promote or inhibit cell growth in various normal and tumor cells. We addressed the effects of exogenous OSM on the proliferation and invasion of human astroglioma cells. In addition, we investigated one of the possible mechanisms involved: modulation of matrix metalloproteinase (MMP) expression and enzymatic activity. We found that OSM inhibited the proliferation of two human astroglioma cell lines (CH235‐MG and U87‐MG), and that this effect was not due to apoptosis. The inhibitory effect of OSM on proliferation was mediated through the gp130/OSMRβ receptor complex. To extend these findings, we analyzed the effects of OSM on primary tumor cells from glioblastoma patients. OSM suppressed the proliferation of primary glioblastoma cells, but not that of normal astrocytes. Interestingly, OSM did not suppress astroglioma cell invasion. This may be due to the differential regulation of MMPs by OSM. We found that OSM inhibited the constitutive expression of MMP‐2, while MMP‐9 expression was enhanced in astroglioma cell lines. We conclude that OSM inhibits proliferation of human astroglioma cells and primary glioblastoma cells via the gp130/OSMRβ receptor complex. However, OSM does not affect the invasive capacity of the astroglioma cells, which may be due to the divergent effects of OSM on MMP‐2 and MMP‐9 expression. Collectively, these findings suggest a complex role for OSM in astroglioma biology. © 2005 Wiley‐Liss, Inc.
Optimisation of microwave digestion for determination of Fe, Zn, Mn and Cu in various legumes by flame atomic absorption spectrometry
Authors: Erdoğan Selim , Erdemoğlu Sema B , Kaya Satılmış
Published: October 2005

Fe, Zn, Mn and Cu levels in three Turkish legumes, kidney bean (Phaseolus vulgaris L.), lentil (Lens esculenta) and chickpea (Cicer arietinum), were determined by flame atomic absorption spectrometry. Dissolution conditions in the microwave‐assisted wet digestion method were studied by investigating several variables, including type of acid mixture, acid volume, digestion time, microwave power input and sample weight. Comparison with conventional wet acid digestion was also made. In order to check the element losses during digestion and the accuracy of the results, all tests were repeated after the addition of a spiked standard element solution to the legume sample. The microwave‐assisted digestion procedure optimised for kidney bean was adapted for lentil and chickpea. Fe, Zn, Mn and Cu concentrations (mg per 100 g sample) were determined in kidney bean as 6.27 ± 0.94, 2.23 ± 0.36, 1.64 ± 0.14 and 0.99 ± 0.19, in lentil as 8.24 ± 1.11, 2.46 ± 0.06, 1.17 ± 0.19 and 1.01 ± 0.28 and in chickpea as 6.00 ± 1.40, 2.21 ± 0.14, 1.60 ± 0.43 and 0.58 ± 0.18 respectively. Copyright © 2005 Society of Chemical Industry
A phase I/II study of doxorubicin, ifosfamide, etoposide and interval methotrexate in patients with poor prognosis osteosarcoma
Authors: McTiernan Anne , Meyer Tim , Michelagnoli Maria P. , Lewis Ian , Whelan Jeremy S.
Published: October 2005

Background

The prognosis for patients with metastatic or axial‐skeletal osteosarcoma is poor. A phase I/II study was conducted of intensive chemotherapy with interval methotrexate, to assess the feasibility, response rate and toxicity in this group of patients.

Patients and Methods

Thirteen patients, median age 18 (range: 8–34), with metastatic or axial‐skeletal osteosarcoma were treated with ifosfamide 2.5 g/m2, etoposide 150 mg/m2, and doxorubicin 20 mg/m2 on days 1–3, every 21 days, with interval methotrexate 12 g/m2 given on day 14, for a maximum of eight cycles. Surgery to the primary was considered after four cycles for those with operable disease, or together with metastatic disease at completion of chemotherapy in those with inoperable tumours.

Results

A total of 85 cycles were given, median 6 per patient (range: 4–8). Only 6 of the 13 patients completed all 8 cycles of chemotherapy. Forty‐eight cycles (56%) required a dose reduction. The principal toxicity was myelosuppression, with a median nadir neutrophil count of 0.1 (range: 0–4.1). Grade 3 or 4 infection was seen in 41 cycles (48%). Histological response was assessable in seven patients, all of whom achieved a ≥90% necrosis. Radiological response rate, evaluable in seven patients with lung metastases, was 43%. All but one patient has had subsequent disease progression or relapse, with a median event free survival of 13 months (range: 5–53).

Conclusion

This regimen was associated with responses, but these were not sustained. Substantial toxicity was seen, preventing optimal delivery. More effective, less toxic regimens are needed in this group of patients. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
Diagnosis and treatment of thrombosis in children: General principles
Authors: Young Guy
Published: October 2005

Thrombosis is an increasingly recognized complication occurring primarily in children with serious underlying conditions and most often associated with intravenous catheters. There are few clinical trials available to guide the decision‐making in the diagnosis and treatment of thrombosis. Although there are published guidelines which suggest how to manage such patients, they are based on data from adult studies and uncontrolled pediatric studies and it is unclear how widely these guidelines are utilized in clinical practice. What is clear is that many additional studies are needed to provide the data required to make evidence‐based decisions. Nevertheless, patients today are being diagnosed with thrombosis and must be treated. Diagnosis is based largely on various diagnostic‐imaging methods. While Doppler ultrasonography is non‐invasive and relatively inexpensive, its sensitivity for the upper venous system is poor. Venography/angiography, the most sensitive method to diagnose venous/arterial thrombosis is underutilized due to the need for peripheral venous access for venography and arterial catheterization for angiography as well as interventional radiology. Newer methods such as computed tomography and magnetic resonance imaging are useful for large vessel disease but are not validated in pediatrics. Treatment is based on the methods that are best at restoring circulation rapidly balanced by the risk for bleeding. Both thrombolysis and anticoagulation can be utilized with the circumstances of each individual patient dictating the choice. The field of pediatric thrombosis continues to advance with numerous new studies currently underway or being planned. In the near future, the results of these studies will allow for better management of pediatric patients with thrombosis. © 2005 Wiley‐Liss, Inc.
Cancer surveillance and control in adolescents—similarities and contrasts between Canada and the United States
Authors: Barr Ronald D. , Greenberg Mark L.
Published: October 2005

Opportunities for cancer prevention in adolescents range from limitation of sun exposure to the use of human papillomavirus vaccines. Those who develop malignant disease experience longer waiting times for diagnosis and treatment than do children, especially when referred to adult treatment centers, and they are less frequently enrolled in clinical trials. More attention to developmentally appropriate psychological support, enhancement of compliance/adherence, health promotion, and palliative care is needed. Improving cancer surveillance and control in adolescents in North America will require co‐ordinated national efforts, involving pediatric and adult health care providers, institutions, and multiple levels of government. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
Dynamic light scattering of semidilute hydrophobically modified alkali‐soluble emulsion solutions with different lengths of poly(ethylene oxide) spacer chain
Authors: Dai Sheng , Chiu Tam Kam , Jenkins Richard D.
Published: October 2005

Semidilute solutions of hydrophobically modified alkali‐soluble emulsion (HASE) were examined by dynamic light scattering and rheological techniques. For the model polymer without associative macromonomer, twoq2dependent diffusional modes were detected in the decay time distributions. With increasing hydrophobicity of the associative macromonomer, the narrow fast peak was substituted by a shallow broad peak and only oneq2dependent slow mode could be accurately detected, which indicated that the heterogeneity of these associated clusters increases with increasing carbon number. The bulk steady‐shear viscosity exhibits similar results to the diffusion coefficients of the aggregate observed from light scattering measurements. The length of poly(ethylene oxide) (PEO) spacer chain alters the solution properties as well as the associative cluster structure. With increasing length of PEO spacer chain, intramolecular association was substituted by intermolecular association. For EO segment larger than 32 units, intramolecular association dominates, where the formation of HASE aggregates is controlled by the balance of electrostatic repulsion and hydrophobic attraction. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3288–3298, 2005
A simplified method of preparing phosphoric acid for stable isotope analyses of carbonates
Authors: Burman Johan , Gustafsson Owe , Segl Monika , Schmitz Birger
Published: October 2005

In order to produce CO2 for stable isotope analyses (δ18O and δ13C), carbonate samples are commonly digested in phosphoric acid. The acid recipe here presented is based on phase shifting crystalline orthophosphoric acid of pro‐analysis quality to a liquid state through heating, followed by pre‐vacuum treatment during a start‐up procedure before mass analyses for common acid bath preparation, or adding a small amount of phosphoric pentoxide for single drop equipments, respectively. This methodology results in a final acid concentration of 104%. Copyright © 2005 John Wiley & Sons, Ltd.
Automated assignment of high‐resolution collisionally activated dissociation mass spectra using a systematic bond disconnection approach
Authors: Hill Alastair W. , Mortishire‐Smith Russell J.
Published: October 2005

An essential component of the process of characterising chemical unknowns via mass spectrometry is the analysis of collisionally activated dissociation (CAD) mass spectra. Existing tools for the automated assignment of CAD spectra typically use a rule‐based approach which identifies those bonds that are likely to break. While valuable, the failure of explicitly rule‐based approaches to suggest rationalisations for a significant proportion of observed product ions led us to develop an alternative approach (elucidation of product ion connectivity, EPIC) based on high‐resolution mass spectrometry, systematic bond disconnection of the precursor structure, and ranking of the resulting substructures. We exemplify this approach with a reanalysis of published MS/MS data for two compounds taken from the literature. Copyright © 2005 John Wiley & Sons, Ltd.
In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys
Authors: Wilcox Kristin M. , Kimmel Heather L. , Lindsey Kimberly P. , Votaw John R. , Goodman Mark M. , Howell Leonard L.
Published: October 2005

Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. Similar to cocaine, other local anesthetics bind to the dopamine transporter (DAT) and inhibit DA uptake in rodent and monkey brain. Additionally, local anesthetics are self‐administered in rhesus monkeys, indicative of abuse liability. The present study examined the reinforcing and DAT effects of the local anesthetics dimethocaine, procaine and cocaine using in vivo techniques. Monkeys were trained to respond under a second‐order schedule for i.v. cocaine administration (0.10 or 0.30 mg/kg/infusion). When responding was stable, dimethocaine (0.030‐1.7 mg/kg/ infusion) or procaine (0.10‐10 mg/kg/ infusion) was substituted for the cocaine training dose. Dimethocaine administration produced higher response rates compared with that of procaine, and was a more potent reinforcer. Drug effects on behavior were related to DAT occupancy in monkey striatum during neuroimaging with positron emission tomography (PET). DAT occupancy was determined by displacement of 8‐(2‐[18F]fluroethyl)2β‐carbomethoxy‐3β‐(4‐chlorophenyl)nortropane (FECNT). DAT occupancy was between 66 and 82% and <10‐41% for doses of dimethocaine and procaine that maintained maximum response rates, respectively. Finally, in vivo microdialysis in awake subjects determined drug‐induced changes in extracellular DA in the caudate nucleus. There was close correspondence between peak increases in DA and DAT occupancy. Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques. The results further support a role for the DAT in the abuse liability of local anesthetics. Synapse 58:220–228, 2005. © 2005 Wiley‐Liss, Inc.
3,4‐Methylenedioxymethamphetamine (MDMA) enhances the release of acetylcholine by 5‐HT4and D1receptor mechanisms in the rat prefrontal cortex
Authors: Nair Sunila G. , Gudelsky Gary A.
Published: October 2005

3,4‐Methylenedioxymethamphetamine (MDMA), an amphetamine analog, has been shown recently to increase the release of acetylcholine (ACh) in the prefrontal cortex (PFC). The present study further characterizes the stimulatory effect of MDMA on cortical ACh release and examines the role of serotonin (5‐HT) and dopamine (DA) receptors in this response. The extracellular concentration of ACh was increased dose‐dependently and similarly by the (+) and (−) enantiomers of MDMA (5 and 20 mg/kg, i.p.). The systemic administration of the 5‐HT4antagonist SDZ 205,557 (1 mg/kg, i.p.), but not the 5‐HT2A/2B/2Cantagonist LY‐53,857 (3 mg/kg, i.p.), significantly decreased cortical ACh release induced by MDMA. The MDMA‐induced increase in the extracellular concentration of ACh also was significantly blunted in rats treated with the D1receptor antagonist SCH 23390 (0.5 mg/kg, i.p.). The extent to which the coadministration of SDZ 205,557 and SCH 23390 suppressed the MDMA‐induced release of ACh in the PFC was no greater than that produced by either antagonist alone. These results suggest that the 5‐HT4and D1receptor subtypes contribute to the mechanism by which MDMA increases ACh release in the PFC. Synapse 58:229–235, 2005. © 2005 Wiley‐Liss, Inc.
Cesarean plus anoxia at birth induces hyperresponsiveness to locomotor activity by dopamine D2 agonist
Authors: Juárez Ismael , De La Cruz Fidel , Zamudio Sergio , Flores Gonzalo
Published: October 2005

Transient global anoxia after Cesarean birth in rats may produce alterations in the subcortical DA function and related behaviors. The reports only tested the behavioral changes induced by a general DA agonist, such as amphetamine or apomorphine, in adult rats. Here we investigated the role of perinatal anoxia on the locomotion induced by a specific dopamine (DA) agonist and its relation to the DA D1‐like and D2‐like receptors, measured by autoradiography at two different ages, prepubertal (35 days old, P35) and postpubertal (60 days old, P60). Cesarean birth with or without (C‐only) an additional period of 10 min of the anoxia was done in Sprague‐Dawley rats, and the effects of the DA D1‐like and D2‐like agonist and their receptors were studied at P35 and P60. In addition, a third group of animals born vaginally served as the control. The quantitative autoradiography study of the DA D1‐like and D2‐like receptors revealed an enhancement of the DA D1‐like receptor levels in the nucleus accumbens (NAcc) and dorsolateral part of the caudate–putamen in the prepubertal C‐only animals. The postpubertal C‐only rats showed a decrease in the levels of DA D2‐like receptors in the NAcc. However, quinpirole, a DA D2 agonist (0.125 and 0.25 mg/kg, s.c.), induced a dose‐dependent increase of the locomotor activity in the animals born by Cesarean with anoxia at birth at both ages. Our results suggest that Cesarean with or without anoxia at birth may mediate differently the neurodevelopmental aspects of the dopaminergic system before and after puberty. Synapse 58:236–242, 2005. © 2005 Wiley‐Liss, Inc.
Temperature insensitivity of short‐term adaptation in single‐units of the chick cochlear nerve
Authors: Crumling Mark A. , Saunders James C.
Published: October 2005

Short‐term adaptation in acoustically stimulated chick cochlear nerve fibers has recently been shown to have similar kinetics as the readily‐releasable vesicle pool in patch‐clamped chick hair cells, suggesting that short‐term adaptation depends on the dynamics of hair cell exocytosis. Our understanding of the relationship between these two phenomena has been hampered by differences in the temperatures at which the two types of data have been collected. In this report, the effect of temperature on short‐term adaptation was studied in single‐units of the chick cochlear nerve. Compared to units recorded at 38–41°C, spontaneous and evoked firing rates were markedly decreased when the temperature was lowered to 28–32°C, but the rate of short‐term adaptation during 100 ms tone bursts was relatively unchanged, with a temperature Q10, of ∼1.2. The continued similarity of the adaptation time‐constant of cooled units to vesicle depletion kinetics in chick hair cells measured at room temperature suggests that comparison of in vitro hair cell exocytosis and in vivo cochlear nerve firing properties may not be confounded by temperature differences between the two approaches. Synapse 58:243–248, 2005. © 2005 Wiley‐Liss, Inc.
N‐[18F]4′‐fluorobenzylpiperidin‐4yl‐(2‐fluorophenyl) acetamide ([18F]FBFPA): A potential fluorine‐18 labeled PET radiotracer for imaging sigma‐1 receptors in the CNS
Authors: Mach Robert H. , Gage H. Donald , Buchheimer Nancy , Huang Yunsheng , Kuhner Ross , Wu Li , Morton Thomas E. , Ehrenkaufer Richard L.
Published: October 2005

A series of brain uptake studies and PET imaging studies were conducted with the σ1 selective imaging agent, [18F]FBFPA. The results of the study indicate that this radiotracer readily crosses the blood‐brain barrier and labels σ1 receptors in vivo. In vivo blocking studies with a σ1 selective ligand and a nonselective σ1/σ2 receptor ligand indicates that [18F]FBFPA labels σ1 and not σ2 receptors in rodent brain. PET imaging studies demonstrated a high uptake in regions of rhesus monkey brain having a high density of σ1 receptors. The uptake of [18F]FBFPA was displaced by the sigma ligand, haloperidol (1 mg/kg, i.v.). In vivo blocking studies indicate that the progesterone blocked the brain uptake of [18F]FBFPA in rat brain. These data indicate that [18F]FBFPA is a potential radiotracer for imaging σ1 receptors in the CNS in vivo with PET. Synapse 58:267–274, 2005. © 2005 Wiley‐Liss, Inc.
Prediction and validation of microRNAs and their targets
Authors: Bentwich Isaac
Published: October 2005

MicroRNAs are short non‐coding RNAs that inhibit translation of target genes by binding to their mRNAs, and have been shown to play a central role in gene regulation in health and disease. Sophisticated computer‐based prediction approaches of microRNAs and of their targets, and effective biological validation techniques for validating these predictions, now play a central role in discovery of microRNAs and elucidating their functions.
A 100‐year (1901–2000) global retrospective estimation of the terrestrial water cycle
Authors: Hirabayashi Y. , Kanae S. , Struthers I. , Oki T.
Published: October 2005

A 100‐year off‐line simulation using a land surface model (LSM) was completed. The long‐term terrestrial water fluxes were estimated well using a LSM driven by long‐term atmospheric forcing data that were stochastically estimated from monthly mean time series of precipitation and temperature. While high correlations between predicted and observed annual runoff are obtained at many basins globally, correlations are low in dry areas and in cool‐temperate zones. These deficiencies of the simulation point out which model processes should be investigated, which can lead to improved representation of land surface processes in future LSMs from a global viewpoint. Annual snow covered area in North America and northern Europe and annual summer soil moisture in Mongolia were successfully replicated by the model. The descending trend of snow covered area in North America and Europe and the increasing trend of summer soil moisture in Mongolia, that were indicated by previous studies, were also replicated by the simulation. With the benefit of 100‐year simulation results for these variables, however, these trends appear to reflect natural long‐term variability rather than systematic changes in hydroclimatological condition. The long‐term estimation of hydrological components, such as annual and inter‐annual variation of runoff, snow and soil moisture, would be useful for examining behaviors of a LSM. The methodology used in this study also has applicability for long‐term water resources assessment in poorly gauged basins, where long‐term atmospheric data are only available at a monthly scale, by providing predictions of extreme behavior and long‐term natural variability in various hydrological components.
Development of subaqueous barchanoid‐shaped dunes due to lateral grain size variability in a tidal inlet channel of the Danish Wadden Sea
Authors: Ernstsen Verner B. , Noormets Riko , Winter Christian , Hebbeln Dierk , Bartholomä Alex , Flemming Burg W. , Bartholdy Jesper
Published: October 2005

High‐resolution bathymetry at centimeter‐scale accuracy acquired with a multibeam echo sounder system revealed the existence of barchanoid‐shaped large (i.e., length 10–100 m) to very large (i.e., length >100 m) dunes in the Grådyb tidal inlet channel in the Danish Wadden Sea. The development of these dunes is due to an increase in dune celerity from 12 m/yr in the center of the channel to around 30 m/yr at the sides. This increase in dune celerity can be explained by the fact that dune heights decrease from 3.1 m in the center of the channel to 1.4 m at the sides, as a smaller sediment volume has to be moved per unit time for equal dune celerity. Water depth is uniform across the channel. Likewise, high‐resolution acoustic Doppler current profiler measurements across the channel showed a uniform distribution of both ebb and flood flow. Thus no correlation between dune dimensions and water depth or flow velocity was established. Instead, high‐accuracy bed sampling along the crests of the dunes showed a decrease in mean grain size from 0.63 mm in the center to 0.36 mm at the sides of the channel. The decrease in dune height is ascribed to this decrease in grain size, given that flow depth and flow velocity are uniform across the channel. The lateral decrease in grain size is suggested to result from sorting effects by secondary currents directed from the center toward the sides of the channel in the trough/lee side region of the barchanoid‐shaped dunes.
Acquisition of iron bound to strong organic complexes, with different Fe binding groups and photochemical reactivities, by plankton communities in Fe‐limited subantarctic waters
Authors: Maldonado Maria T. , Strzepek Robert F. , Sander Sylvia , Boyd Philip W.
Published: October 2005

Though it is clear that plankton in oceanic regions access iron bound to strong organic ligands, the mechanism mediating the release of iron from these complexes remains unresolved. In this study, we aim to elucidate the mechanisms of organic iron acquisition by plankton in subantarctic waters. In particular, we investigated the importance of photochemistry in mediating the reductive dissociation of iron from organic complexes, using naturally occurring ligands, and model iron complexes, with different iron‐binding groups and photoreactivities. Our results demonstrate that iron within the model ligands is available for uptake and growth by indigenous plankton, but that photolability of these complexes does not determine iron bioavailability. In contrast, light significantly enhances iron acquisition from the in situ ligands, suggesting that the in situ iron ligands are photolabile, and that photochemistry in surface waters may play a significant role in iron uptake from the dissolved organic iron pool by oceanic plankton.