bluuebunny/crossref_metadata_2025 huggingface dataset:
Silicone elastomers with controlled surface composition using argon or hydrogen plasma treatment
Authors: Olander Björn , Wirsén Anders , Albertsson Ann‐Christine
Published: September 2003

Plasma treatment of poly(dimethyl siloxane) (PDMS) leads to changes in the surface composition that can be followed by X‐ray photoelectron spectroscopy (XPS). Prolonged plasma treatment in argon or hydrogen leads to an increase in oxygen, a decrease in carbon, and only minor changes in the silicon content. The extent of the change in elemental composition is dependent on the plasma conditions (e.g., the power and pressure during the treatment). We have determined how these parameters influence the surface composition of PDMS exposed to argon and hydrogen microwave plasma as a function of treatment time. A model has been developed describing the extent of change in surface composition under different plasma conditions. The power had a large impact on the rate of change in elemental surface composition, whereas the pressure had only a minor influence. We show that the rate of change in elemental composition can be described by one factor common for all treatments and one factor specific for each plasma condition of power, pressure, and gas. Using this model we can determine the plasma parameters and treatment time to obtain any desired extent of surface modification. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1378–1383, 2003
Preparation and characterization of chitosan/Cu(II) affinity membrane for urea adsorption
Authors: Liu Jiahao , Chen Xin , Shao Zhengzhong , Zhou Ping
Published: September 2003

We used silica particles as a porogen to prepare macroporous chitosan membranes and subsequently prepared macroporous chitosan/Cu(II) affinity membranes for urea adsorption. The morphology, porosity, Cu(II) adsorption capacity, and swelling ratio of the macroporous membrane were measured. SEM photographs show the pores in the membrane dispersed uniformly, a feature that didn't change much after the adsorption of Cu(II). The porosity of the membrane had a maximum value when the silica/chitosan ratio was about 12. The Cu(II) adsorption capacity in the membrane leveled off when the initial concentration of CuSO4 solution exceeded 5 × 10−2 mol/L. The macroporous chitosan/Cu(II) affinity membrane was successfully used for urea adsorption. The maximum urea adsorption capacity was 78.8 mg/g membrane, which indicates that the membrane has a great potential for hemodialysis for urea removal. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1108–1112, 2003
Preparation and characteristics of poly(propylene glycol) and poly(acrylic acid) interpenetrating polymer network hydrogels
Authors: Kim Seon Jeong , Lee Ki Jung , Kim In Young , An Kay Hyeok , Kim Sun I.
Published: September 2003

Interpenetrating polymer network (IPN) hydrogels based on poly(propylene glycol) diacrylate macromer and poly(acrylic acid) (PAAc) were prepared by UV irradiation and characterized by swelling in water. The swelling behavior of these IPNs was analyzed in buffer solution at various temperatures. Swelling ratios of all IPNs were relatively high and showed reasonable sensitivity to temperature. Hydrogels showed both positive and negative swelling behavior depending on PAAc content. PA22 and PA13 showed positive and PA31 showed negative temperature‐sensitive swelling behavior. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1384–1388, 2003
Water sorption of poly(vinyl alcohol)/ poly(diallyldimethylammonium chloride) interpenetrating polymer network hydrogels
Authors: Kim Seon Jeong , Yoon Seoung Gil , Lee Young Moo , An Kay Hyeok , Kim Sun I.
Published: September 2003

Temperature‐responsive interpenetrating polymer network (IPN) hydrogels constructed with poly(vinyl alcohol) and poly(diallyldimethylammonium chloride) using the sequential IPN method were studied. The characteristics of IPN hydrogels were investigated using the dynamic vapor sorption system. IPN hydrogels exhibited a relatively high sorption ratio, 180–360% at room temperature. The sorption ratio of hydrogels depended on temperature. Diffusion coefficients were calculated according to the Fickian Law at several temperatures. The apparent activation energy was 5.43 kJ mol−1, which corresponds to typical diffusion processes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1389–1392, 2003
Study of the thermal stability of glucose oxidase in the presence of water‐soluble polymers
Authors: Godjevargova T. , Vasileva N. , Letskovska Zl.
Published: September 2003

The thermal stability of glucose oxidase (GOD) in solutions containing water‐soluble hydrolyzed polyacrylonitrile (HPAN) and polyoxyethylene (POE) was studied as a function of time and temperature between 28 and 60°C. The results were compared with the thermal stability of GOD in solutions without polymers. The polymers studied were found to increase the enzyme thermal stability. The influence of the concentration of the water‐soluble polymers on enzyme thermal stability was also studied. The best protection effect on enzyme thermal stability had 3 wt % solution of HPAN and 1 wt % solution of polyoxyethylene. Solutions with higher concentrations led to a quick deactivation of the enzyme. It was proved that the effect of 3 wt % HPAN solution was stronger than the effect of 1 wt % POE (59.0 versus 52.0%). The thermal transition of the enzyme was studied in both the presence and the absence of HPAN by DSC. The melting temperature of GOD in the presence of HPAN was shifted to an 11°C higher value. This sustained the supposition that HPAN increases the thermostability of GOD. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1393–1397, 2003
Preparation of conducting composites of polypyrrole using supercritical carbon dioxide
Authors: Abbett Kimberly F. , Teja Amyn S. , Kowalik Janusz , Tolbert Laren
Published: September 2003

Supercritical carbon dioxide, saturated with pyrrole, was brought into contact with oxidant‐impregnated films of poly(chlorotrifluoroethylene) (PCTFE), crosslinked poly(dimethylsiloxane) (PDMS), poly(methyl methacrylate) (PMMA), and porous crosslinked polystyrene (PS) in order to form conducting composites via the in situ polymerization of pyrrole. The two nonporous hosts—PCTFE and crosslinked PDMS—did not form conducting composites with polypyrrole (PPy). On the other hand, the electrical conductivity of the PPy composites with carbon dioxide‐swollen PMMA and porous PS ranged from 1.0 × 10−4 S/cm to 3.0 × 10−5 S/cm. In these two cases, the level of pyrrole polymerized on the surface or in the pores of the host polymer was sufficient to attain the interconnected conducting polymer networks necessary for electrical conductivity. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1113–1116, 2003
Antimycobacterial and Antifungal Isosters of Salicylamides
Authors: Waisser Karel , Pešina Milan , Holý Pavel , Pour Milan , Bureš Otakar , Kuneš Jiší , Klimešová Všra , Buchta Vladimír , Kubanová Petra , Kaustová Jarmila
Published: September 2003

A set of 40 derivatives of 3‐hydroxypicolinic acid and 2‐sulfanylbenzoic acid, isosteric to salicylanilides was synthesized. The compounds were evaluated for in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium, Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes and Microsporum gypseum. Structure‐activity relationships of antimycobacterial activity and antifungal activity against T. mentagrophytes and M. gypseum were analyzed by the Free‐Wilson method. An increase in antimycobacterial activity was observed only for the sulfanylbenzoic acid derivatives, especially those with the benzyl moiety. The antifungal activity was not significant.
3‐Alkyl‐ and 3‐Aryl‐(7‐oxo‐7H‐furo[3, 2‐g]chromen‐5‐yl)alkanoic Acids as Inhibitors of Leukotriene B4 Biosynthesis
Authors: Körner Paul
Published: September 2003

The synthesis and biological properties of 3‐alkyl‐and 3‐aryl‐(7‐oxo‐7H‐furo [3, 2‐g]chromen‐5‐yl)alkanoic acids are described. The compounds were evaluated for their ability to inhibit soybean 15‐lipoxygenase (15‐LO) and the production of leukotriene B4 (LTB4) in bovine polymorphonuclear leukocytes. The furocoumarins were further investigated for their lipophilicity and their capacity to photobleach N, N‐dimethyl‐p‐nitrosoaniline (RNO) after irradiation with UVA light. The synthesised furocoumarins showed only a moderate ability to inhibit the 15‐LO and the production of LT B4. The 3‐alkyl substituted furocoumarins had a higher capacity to photobleach RNO than then the 3‐aryl substituted furocoumarinso. The inhibitory activity of the newcompounds was quite modest in comparison to other known inhibitors of 15‐LO and LTB4 production. Nevertheless, they may provide the basis for the development of more potent antiinflammatory potential photoreactive furocoumarins.
Structure‐Activity Studies of Novel Amidine Analogues of Chlorambucil: Correlation of Cytotoxic Activity with DNA‐Binding Affinity and Topoisomerase II Inhibition
Authors: Bielawska Anna , Bielawski Krzysztof , Wołczyński Sławomir , Anchim Tomasz
Published: September 2003

A series of amidine analogues of chlorambucil (9—12), where 5‐[4‐(N‐alkylamidino)phenyl]‐2‐furancarboxamide and the chlorambucil moiety are linked by a NH(CH2)2NH chain, was synthesized and their cytotoxicity has been tested against the growth of human breast cancer MCF‐7 cells. Evaluation of the cytotoxicity of compounds 9—12 employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA demonstrated that these conjugates were more active than chlorambucil. Data from the ethidium displacement assay indicated that these compounds bind in the minor groove of DNA and show moderate specificity for AT base pairs. Compounds 9—12 were potent topoisomerase II inhibitors, with 50% inhibitory concentrations (IC50)ranging from 10 to 40 μM. The cytotoxicity of the compounds 9—12 correlates with their DNA‐binding affinities and their relative potency as topoisomerase II inhibitors. Altogether, these data suggest (i) that the cytotoxic activity of compounds 9—12 may be due to the combined effects of alkylation, DNA‐minor groove binding, and (ii) that N‐(2‐aminoethyl)‐5‐(4‐N‐alkylamidinophenyl)‐2‐furancarboxamides (5—8) ligands are suitable linkers that favors DNA targeting by chlorambucil derivatives.
Studies on Novel 7‐Acyl‐5‐chloro‐2‐oxo‐3H‐benzoxazole Derivatives as Potential Analgesic and Anti‐Inflammatory Agents
Authors: Ünlü Serdar , Baytas Sultan Nacak , Kupeli Esra , Yesilada Erdem
Published: September 2003

In this study, a series of (7‐acyl‐5‐chloro‐2‐oxo‐3H‐benzoxazol‐3‐yl)alkanoic acid derivatives were synthesized and evaluated for their analgesic and anti‐inflammatory activities by using the p‐benzoquinone‐induced writhing test and the carrageenan hind paw edema model, respectively. Acetic acid‐induced peritoneal capillary permeability test and serotonin‐induced hind paw edema test were also employed for the most active compounds. The test results indicated that (7‐acyl‐2‐oxo‐3H‐benzoxazol‐3‐yl)alkanoic acids (Compounds 6 a—c, 8 a—c, 10 a—c) were equally or more potent analgesic and anti‐inflammatory agents than aspirin and indomethacin respectively. The compounds 8a and 8c, but not 8b have the longest carbon chain on alkanoic acid moiety did not induce gastric lesion in mice.
New Cyanopeptide‐Derived Low Molecular Weight Inhibitors of trypsin‐like Serine Proteases
Authors: Radau Gregor , Schermuly Sonja , Fritsche Alexandra
Published: September 2003

This paper deals with the design, syntheses, and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98‐B (1) as a lead structure, we have developed and synthesised new, selective acting inhibitors of serine proteases (RA‐1005 and RA‐1009, which are suitable targets for further structure‐activity studies.
Novel High Energy Intermediate Analogues with a Triazasterol Structure as Potential Ergosterol Biosynthesis Inhibitors IV: Antimicrobial Activity of Mono‐, Bi‐, and Tricyclic 8, 13, 15‐Triazasteroid Analogues Including the Synthesis of Novel 4‐Alkylamino‐ and 4‐Alkenylamino‐9‐hydroxypyrimidoisoquinolines
Authors: Gößnitzer Edith , Punkenhofer Asbjörn , Ryder Neil S.
Published: September 2003

4‐Alkylamino‐and 4‐alkenylamino‐9‐hydroxy‐1, 6, 7, 11b‐tetrahydro‐2H‐pyrimido[4, 3‐a]isoquinolines were designed as inhibitory tricyclic triaza‐analogues of carbocationic high energy intermediates (HEI) of enzymes involved in fungal ergosterol biosynthesis. Various routes for effective synthesis of 9‐hydroxypyrimidoisoquinolines from 9‐methoxythiones were investigated. The ether cleavage of 9‐methoxy‐pyrimidoisoquinolines, a key step in the synthesis, was carried out using various protocols. The structures of the obtained 9‐hydroxy compounds were confirmed using homo‐ and hetero‐nuclear correlated 1D and 2D NMR experiments. In vitro antifungal susceptibility tests of the alkylaminohydroxypyrimidoisoquinolines revealed weak to good antimycotic effects. The maximum antifungal efficacy was found for 4‐[(3R)‐6‐isopropyl‐3‐methyl‐6‐heptenylamino]‐9‐hydroxypyrimidoisoquinoline. Furthermore, the in vitro activities of the newly synthezised 9‐hydroxypyrimidoisoquinolines and of a series of prepared 8, 13, 15‐triazasteroid analogues (N‐alkyl‐N′‐(phenethyl‐ and cyclohexenylethyl)guanidines, N2 ‐and N2, 4‐substituted imidazolin‐2‐amines, and N4‐alkylaminopyrimidoisoquinolines) against representatives of gram‐positive and gram‐negative bacteria were investigated. The compounds showed significant antibacterial effects against gram‐positive bacteria.
Characterization of the Biochemical Effects of New 1, 8‐Naphthyridine Derivatives, β‐Receptor Antagonists, in Ventricular Myocytes
Authors: Al jamal Jalal A. , Badawneh Muwaffag
Published: September 2003

Novel derivatives of 1, 8‐naphthyridine were synthesized from 7‐amino‐2‐hydroxy‐4‐morpholinomethyl‐1, 8‐naphthyridine. The ability of the synthesized compounds to inhibit isoproterenol(ISO)‐induced phosphorylation of phospholamban (PLB) was assessed. Their ability to block both β1 and β2 receptors almost completely abolished all ISO effects on phosphorylation of PLB. Analogues with either a 7‐hydroxy‐2‐N‐ethoxycarbonylpiperazine or a 7‐hydroxy‐2‐piperazine substituent, designated as 6 and 9 respectively, showed a higher affinity for β1 receptor than that of the methoxy derivatives 12 and 13. However, treatment with 30 μM 9 and 1mM 13 lead to comparable levels of PLB phosphorylation. The reduction to 6‐amino derivatives 10 and 17 led to compounds possessing β2 receptor blocking properties. The ability of the synthesized compounds to inhibit forskolin‐stimulated cAMP production was also studied. Together, these results suggest that the 1, 8‐naphthyridine parent structure can be modified, to produce compounds with increased activity whose effect in rat appears to be more clearly related to antagonism of β1‐rather than β2‐adrenergic receptors.
Overlap in bibliographic databases
Authors: Hood William W. , Wilson Concepción S.
Published: September 2003

Bibliographic databases contain surrogates to a particular subset of the complete set of literature; some databases are very narrow in their scope, while others are multidisciplinary. These databases overlap in their coverage of the literature to a greater or lesser extent. The topic of Fuzzy Set Theory is examined to determine the overlap of coverage in the databases that index this topic. It was found that about 63% of records in the data set are unique to only one database, and the remaining 37% are duplicated in from two to 12 different databases. The overlap distribution is found to conform to a Lotka‐type plot. The records with maximum overlap are identified; however, further work is needed to determine the significance of the high level of overlap in these records. The unique records are plotted using a Bradford‐type form of data presentation and are found to conform (visually) to a hyperbolic distribution. The extent and causes of intra‐database duplication (records duplicated in the one database) are also examined. Finally, the overlap in the top databases in the dataset were examined, and a high correlation was found between overlapping records, and overlapping DIALOG OneSearch categories.
The experience of libraries across time: Thematic analysis of undergraduate recollections of library experiences
Authors: Kracker Jacqueline , Pollio Howard R.
Published: September 2003

To understand the human experience of libraries and the implications this understanding has for library use and service, education, and design, 118 undergraduate students were asked to list three personally memorable incidents concerning library use. Following this, they were asked to write a short narrative of one of these experiences. Incidents reported by participants ranged from preschool to college age, and content analysis indicated that a majority took place at two or more grade levels, sometimes as early as the participant's first (preschool) visit to a library. Phenomenological analysis of individual narratives produced a thematic structure for each of the four grade levels represented in the data: elementary school and younger, middle school, high school, and college/adult. Themes common across all four levels include Atmosphere, Size and Abundance, Organization/Rules and Their Effects on Me, and What I Do in the Library. A theme of Memories was unique to narratives that took place during elementary and younger age levels. Although all remaining themes were noted across age levels, the relative importance of various themes and subthemes was different at different ages. Implications of the thematic structure for library practice are discussed.
Bibliomining for automated collection development in a digital library setting: Using data mining to discover Web‐based scholarly research works
Authors: Nicholson Scott
Published: September 2003

This research creates an intelligent agent for automated collection development in a digital library setting. It uses a predictive model based on facets of each Web page to select scholarly works. The criteria came from the academic library selection literature, and a Delphi study was used to refine the list to 41 criteria. A Perl program was designed to analyze a Web page for each criterion and applied to a large collection of scholarly and nonscholarly Web pages. Bibliomining, or data mining for libraries, was then used to create different classification models. Four techniques were used: logistic regression, nonparametric discriminant analysis, classification trees, and neural networks. Accuracy and return were used to judge the effectiveness of each model on test datasets. In addition, a set of problematic pages that were difficult to classify because of their similarity to scholarly research was gathered and classified using the models. The resulting models could be used in the selection process to automatically create a digital library of Web‐based scholarly research works. In addition, the technique can be extended to create a digital library of any type of structured electronic information.
New knowledge management systems: The implications for data discovery, collection development, and the changing role of the librarian
Authors: Stern David
Published: September 2003

The papers presented at the 2002 Tri‐Society Symposium on Chemical Information highlight questions we should consider as we develop new paradigms for information storage and retrieval systems. These new knowledge management systems will require novel approaches for data discovery, collection development, and the changing role of the librarian. This introductory essay discusses new and challenging integrated tools for data manipulation, the confusing and embryonic differential pricing and package deals for journal materials, and the changing role of the librarian in this rapidly transforming industry.
Making the transition from print to electronic serial collections: A new model for academic chemistry libraries?
Authors: Chrzastowski Tina E.
Published: September 2003

A “new model” academic chemistry library is proposed at the University of Illinois at Urbana‐Champaign (UIUC) in which primary access to journals is electronic, replacing traditional print access, binding, and shelving. Print journals will continue to be purchased and archived unbound in a remote storage facility following unbound display and access for twelve months. The new model, initially proposed by administrative chemistry faculty, was assessed in a feasibility study which looked at the stability, quantity, and quality of electronic journals; it also included a survey of chemistry faculty, a review of internal management data, and an analysis of use of chemistry journals, both print and electronic. The feasibility study found support for the model in every area, but with a few caution flags and speed bumps predicted along the way.
Changing use patterns of print journals in the digital age: Impacts of electronic equivalents on print chemistry journal use
Authors: Vaughan K.T.L.
Published: September 2003

Little data are available that can help librarians solve issues surrounding print versus online journals management, including ascertaining when print journals are no longer needed. This study examines the short‐term effects of online availability on the use of print chemistry journals. The Duke University Chemistry Library gained access to Elsevier titles via ScienceDirect in February 2000. By comparing reshelving data for the print journals from 1999, 2000, and 2001, this study identifies the short‐term changes in journals use that can be attributed to the introduction of ScienceDirect. In the first two years after ScienceDirect was introduced, use of print journals nearly halved. The diminished use of the print collection has important implications for collection management in sci‐tech libraries.
Linking of errata: Current practices in online physical sciences journals
Authors: Poworoznek Emily L.
Published: September 2003

Reader awareness of article corrections can be of critical importance in the physical and biomedical sciences. Comparison of errata and corrigenda in online versions of high‐impact physical sciences journals across titles and publishers yielded surprising variability. Of 43 online journals surveyed, 17 had no links between original articles and later corrections. When present, hyperlinks between articles and errata showed patterns in presentation style, but lacked consistency. Variability in the presentation, linking, and availability of online errata indicates that practices are not evenly developed across the field. Comparison of finding tools showed excellent coverage of errata by Science Citation Index, lack of indexing in INSPEC, and lack of retrieval with SciFinder Scholar. The development of standards for the linking of original articles to errata is recommended.
Managing tradeoffs in the electronic age
Authors: Wagner A. Ben
Published: September 2003

An overview of the development of electronic resources over the past three decades is provided, discussing key features, disadvantages, and benefits of traditional online databases and CD‐ROM and Web‐based resources. This analysis of gains and losses as information resources have shifted to the Internet provides a basis for identifying key issues in the decision to shift collections and resources toward purely digital formats. Ownership of content, licensing terms, and the proliferation of user interfaces are especially important and still unresolved concerns.
Intermediary's information seeking, inquiring minds, and elicitation styles
Authors: Wu Mei‐Mei , Liu Ying‐Hsang
Published: September 2003

The current research explores how intermediaries seek information from patrons, in particular by analyzing intermediaries' elicitation utterances through three dimensions—linguistic forms, utterance purposes, and communicative functions—to determine whether indeed any dimension appeared consistently, to be called “elicitation styles.” Five intermediaries from four academic libraries (three national university libraries, one private university library) and one research institute library participated in the study. Thirty patrons with 30 genuine search requests were recruited; thus, 30 patron/intermediary information retrieval interactions making a total of 30 encounters were collected. Video/audio data were taped. Dialogues between patron and intermediary were transcribed. Statistical analysis revealed three types of elicitation styles among the five intermediaries, labeled, (1) situationally oriented, (2) functionally oriented, and (3) stereotyped. This study seeks an explanation for different elicitation styles. Qualitative analysis was applied to investigate “inquiring minds.” An inquiring mind is termed to represent a mentality or tendency that one elicits certain threads of questions influenced by professional beliefs, individual characteristics, tasks, goals, and interactional contexts in conversation. The results of qualitative analysis specified three modes of inquiring minds of the intermediaries, namely: (1) information problem detection, (2) query formulation process, and (3) database instructions.
Effect of feed restriction on Hershberger and pubertal male assay endpoints
Authors: Marty M. Sue , Johnson Keith A. , Carney Edward W.
Published: September 2003

BACKGROUND: The Hershberger and male pubertal onset assays have been identified as possible Tier I screening tests to detect endocrine‐active compounds (EACs). Both tests rely on changes in reproductive and/or accessory sex gland (ASG) weights in young animals. Because chemical treatment may affect growth rate, the relationship between body weight and reproductive/ASG weights was examined using feed restriction (FR) to produce a targeted 10% decrease in body weight. METHODS: In the male pubertal onset assay, 23‐day‐old rats (12/group) were given ad lib feed or FR until euthanized at 45, 49, 52, 56, or 59 days of age. Despite a 10% body weight differential, pubertal onset was not significantly delayed and testes weights were conserved. Absolute prostate, ventral prostate, seminal vesicle, epididymides, and liver weights were decreased by FR. Relative weights for the prostate, ventral prostate, and seminal vesicles were similar to controls, but relative epididymides and liver weights still exhibited FR‐mediated changes. In the Hershberger assay, male rats (12/group) castrated at 36 days of age were given ad lib feed or FR in the presence or absence of testosterone propionate (T) from 46–55, 50–59, or 56–65 days of age. At 56, 60, and 66 days of age, rats were euthanized. In untreated animals, FR did not alter absolute ventral prostate, seminal vesicles, or Cowper's gland weights; however, absolute and relative weights of the levator ani‐bulbocavernosus muscles (LABC) were affected. In T‐treated animals, absolute organ weights (the ventral prostate, seminal vesicles, LABC, and glans penis) were relatively insensitive to FR. The weight of the Cowper's gland was affected only at 66 days of age. RESULTS: These data show that reproductive and ASG organ weight endpoints in the Hershberger and male pubertal onset assays can be influenced by FR levels that produce a 10% change in terminal body weight. CONCLUSIONS: The establishment of objective criteria for a positive or negative result is problematic due to the confounding effects of body weight on some endpoints. Furthermore, a 10% decrease in body weight seems to be excessive as a requirement for high‐dose toxicity in these assays due to possible indictment of agents that are not EACs, as well as potential masking of EAC effects coincident with body weight changes. Minimally, caution must be used in interpreting assay results in the presence of a 10% body weight change, recognizing the possible confounding effects of this degree of growth suppression. Birth Defects Res B 68:363–374, 2003. © 2003 Wiley‐Liss, Inc.
Pretreatment with periodate‐oxidized adenosine enhances developmental toxicity of inorganic arsenic in mice
Authors: Lammon Carol A. , Le X. Chris , Hood Ronald D.
Published: September 2003

BACKGROUND: Inorganic arsenic, given by injection to pregnant laboratory animals, can induce malformations. Arsenic methylation can be inhibited by periodate‐oxidized adenosine (PAD). Severe human health effects from high chronic arsenic exposure have mainly been reported in populations with significant levels of malnutrition, which may enhance toxicity by diminishing arsenic methylating capacity. This study sought to determine the effect of inhibition of arsenic methylation on the developmental toxicity of arsenic in a mammalian model. METHODS: PAD (100 µM/kg, i.p.), was given to pregnant CD‐1 strain mice 30min before 7.5mg/kg sodium arsenite [As(III)], i.p., or 17.9mg/kg sodium arsenate [As(V)], i.p., on gestation day 8 (GD 8; copulation plug=GD 0). Control dams received As(III), As(V), or PAD alone or were untreated. Test dams were killed on GD 17, and their litters were examined for mortality and gross and skeletal defects. RESULTS: Pretreatment with PAD before either arsenical resulted in increased maternal toxicity and lower fetal weights. Pretreatment also caused higher prenatal mortality, with 8 of 21 and 5 of 17 litters totally resorbed in the PAD plus As(III) and PAD plus As(V) treatment groups, respectively. Significant increases in the incidences of exencephaly, ablepharia, and anomalies of the vertebral centra, sternebrae, and ribs were also associated with PAD pretreatment. Short tail (3 fetuses in 3 litters) was seen only following PAD plus As(III) treatment. CONCLUSIONS: These results demonstrate that the developmental toxicity of inorganic arsenic can be enhanced by PAD, due possibly to inhibited methylation of arsenic. Birth Defects Res B 68:335–343, 2003. © 2003 Wiley‐Liss, Inc.
Comparison of prostate gene expression and tissue weight changes as monitors of antiandrogen activity in GNRH‐inhibited rats
Authors: Nellemann C. , Lefevre P.A. , Ashby J.
Published: September 2003

BACKGROUND: The Hershberger assay for antiandrogens and modifiers of steroid biosynthesis uses surgically‐castrated rats. We described an adaptation of the assay using the GnRH inhibitor Antarelix in place of surgical castration [Ashby J, Lefevre PA, Deghenghi R, Wallis N. Regulatory Toxicology and Pharmacology 34:188–203, 2001], and concomitantly described changes in expression of the androgen‐dependent prostatic genes PBP C3, TRPM‐2, and ODC as a possible complement to gravimetric analysis of the sex accessory tissues (SAT) [Nellemann C, Vinggaard AM, Dalgaard M, Hossaini A, Larsen J‐J. Toxicology 163:29–38, 2001]. METHODS: The present study describes the results of combining these two modifications into a single assay. During the course of these experiments it was shown that SD rats gave similar results to AP rats and that the higher stimulatory dose of testosterone propionate (TP) used in our experiments gave stronger assay responses to FLU than the lower dose of TP used by some earlier investigators. The potent antiandrogen flutamide (FLU) and the weak antiandrogen DDE were used to evaluate this modified assay. RESULTS: For all parameters studied (SAT weights and changes in expression of the 3 prostatic genes) FLU gave the expected positive results. The weak antiandrogen DDE gave variable and mainly non‐reproducible responses. Use of DDE as a weak antiandrogen accelerated assessment of the new assay. CONCLUSIONS: Possible reasons for this failure to detect DDE are discussed, and it is concluded that the modified assay is unsuitable for use in its present form. The use of gene expression analyses together with evaluation of SAT weights is a promising tool as an early and sensitive marker of antiandrogen action, but more work is needed on the choice of time frame as well as the selection of genes to monitor. Birth Defects Res B 68:344–354, 2003. © 2003 Wiley‐Liss, Inc.
Maternal‐fetal distribution and prenatal toxicity of 2,2,4‐trimethyl‐1,2‐dihydroquinoline in the rat
Authors: Sitarek Krystyna , Sapota Andrzej
Published: September 2003

BACKGROUND: Polnoks R (poly‐2,2,4‐trimethyl‐1,2‐dihydroquinoline) is used as an antioxidant in elastomer processing. It is an embryotoxic and fetotoxic agent. This chemical given per os to female rats induces also teratogenic effect but only at doses toxic to the mother. The aim of the study was to evaluate prenatal development and tissue distribution in rats exposed to 2,2,4‐trimethyl‐1,2‐dihydroquinoline (TMDHQ), a monomer of Polnoks R. METHODS: Females were exposed orally to unlabeled TMDHQ during organogenesis at doses 50–400 mg/kg to asses prenatal toxicity and to radiolabeled 14C monomer at a dose 210 mg/kg to evaluate tissues distribution. RESULTS: TMDHQ administered to pregnant females per os at doses 100 mg/kg and higher produced teratogenic effect (cleft palate, wavy ribs, kyphoscoliosis, exencephaly, external hydrocephalus, hydronephrosis, and renal hypoplasia). Peak 14C‐radioactivity was found in mothers' plasma about 10 hr after administration of this compound at dose 210 mg/kg. The accretion of 14C proceeded with a kinetic constant of 0.35 hr −1 and a half‐life of 53.3 hr. Kidneys are the main organs of monomer excretion. The highest concentration of 14C in maternal tissues 24 hr after oral dosing was found in adipose tissue, sciatic nerve, muscles, kidneys, and liver. Radiocarbon retention in fetuses was the highest in kidneys at all time points after dosing. CONCLUSIONS: This study has demonstrated that transplacental exposure to Polnoks R monomer is teratogenic in rats. 14C retention in placenta, amniotic fluid, and fetal tissues indicates that this compound or its metabolites penetrate into placenta to the fetus. Birth Defects Res B 68:375–382, 2003. © 2003 Wiley‐Liss, Inc.
Gastroschisis is caused by the combination of carbon monoxide and protein‐zinc deficiencies in mice
Authors: Singh Jarnail
Published: September 2003

BACKGROUND: Gastroschisis is a rare congenital defect of the abdominal wall. Its occurrence is noted primarily in the offspring of young mothers who often smoke during pregnancy. The incidence of gastroschisis has been increasing in many countries in recent years. The etiology of gastroschisis is not known. METHODS: Pregnant mice of CD‐1 strain were maintained on 17 and 9% protein diets mixed with deficient, normal, or supplemental zinc levels throughout gestation. The dams in each protein‐zinc diet group were randomly divided in two groups. One group was exposed to air (control) and the other to 500 ppm carbon monoxide (CO) in air, in environmental chambers, from gestation days (GD) 8–18. The dams were sacrificed by carbon dioxide asphyxiation on GD 18, and data on malformations was collected. RESULTS: The rates of fetal mortality and malformations were increased by protein and zinc deficiencies. Carbon monoxide exposure also increased fetal mortality. In the low protein group, the rate of fetal mortality was inversely related to the dietary zinc level, and the rate of fetal malformations was highest in the zinc deficient group. The incidence of gastroschisis in the low protein/zinc deficient/CO exposed group was 47%, and 60% of the litters were affected. The incidence of gastroschisis in the rest of the low protein/zinc diets/air or CO groups was 0. CONCLUSION: The data indicates that gastroschisis is caused by the combination of protein‐zinc deficiencies and carbon monoxide exposure during gestation. The finding may be relevant to human populations that experience protein and zinc deficiencies during gestation, and are exposed to CO pollution, or cigarette, or marijuana smoke during pregnancy. Birth Defects Res B 68:355–362, 2003. © 2003 Wiley‐Liss, Inc.
Effects of gestational exposure to ethane dimethanesulfonate in CD‐1 mice: Microtia and preliminary hearing tests
Authors: Tarka‐Leeds Dana K. , Herr David W. , Klinefelter Gary R. , Rogers John M.
Published: September 2003

BACKGROUND: Microtia is a reduction in pinna size, usually seen in humans in conjunction with other medical conditions. We report microtia in CD‐1 mice after gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and adult rat Leydig cell toxicant. METHODS: Time‐pregnant CD‐1 mice were administered 0, 80, or 160 mg EDS/kg on gestation days (GD) 11–17, or 0 or 160 mg EDS/kg on GD 11–13, GD 13–15 or GD 15–17. Pinnae were measured on postnatal days (PND) 4, 8, 18, and 28; and were observed for detachment from birth through PND 8. Branchial‐arch derived skeletal structures and histology of the pinna was examined on PND 4 and 24. Brainstem auditory evoked response (BAER) tests were carried out at approximately PND 160 to determine possible effects on hearing. RESULTS: All offspring of EDS‐treated dams exhibited bilateral, dose‐related decreases in pinna size. Gestational exposure during GD 11–13 produced smaller ears than during GD 13–15 or 15–17, but not as small as the GD 11–17 regimen. Ossification of other pharyngeal arch derivatives was delayed whereas histology was unremarkable. BAER analysis showed a decrease in the proportion of adult offspring producing a quantifiable response to varied auditory stimuli among EDS‐treated litters. CONCLUSIONS: Gestational exposure to EDS affects pinna development in the mouse, with a broad period of sensitivity during the second half of gestation. Microtia induced by EDS may be associated with hearing deficits, suggesting functional importance of pinna size or additional effects of EDS on ear development not detected by morphological examination. Birth Defects Res B68:383–390, 2003. © 2003 Wiley‐Liss, Inc.
Species comparison of anatomical and functional immune system development
Authors: Holsapple Michael P. , West Lori J. , Landreth Kenneth S.
Published: September 2003

The components of the immune system have not been traditionally emphasized as potential target organs in standard developmental and reproductive toxicity (DART) protocols. A number of workshops have been organized in recent years to examine scientific questions that underlie developmental immunotoxicity tests, and the interpretation of results as they relate to human risk assessment. A key question that must be addressed is to determine the most appropriate species and strains to model the developing human immune system. The objective of this review is to compare the anatomical and functional development of the immune system in several species important to either preclinical studies for drug development or safety assessments for chemicals, with what is known in humans. The development of the immune system in humans will be compared to what is known in mice, rats, dogs and nonhuman primates. Birth Defects Res B 68:321–334, 2003. © 2003 Wiley‐Liss, Inc.
In vitro studies of the influence of ELF electromagnetic fields on the activity of soluble and insoluble peroxidase
Authors: Portaccio M. , De Luca P. , Durante D. , Rossi S. , Bencivenga U. , Canciglia P. , Lepore M. , Mattei A. , De Maio A. , Mita D.G.
Published: September 2003

The influence of an extremely low frequency (ELF) magnetic field (50 Hz and 1 mT, EMF) on the activity of a soluble and insoluble horseradish peroxidase (E.C. 1.11.17) has been studied as a function of time. Insoluble derivatives were obtained by enzyme entrapment into two different gelatin membranes or by covalent attachment of the enzyme on two nylon membranes, differently preactivated. Results have shown that the field affects the inactivation rate of the soluble enzyme, while no effects are observed with insoluble derivatives. Since in vivo enzymes are immobilised into the biomembrane bilayer or entrapped into the cytoplasmic mixture, one might speculate that our experimental conditions do not reflect the catalytic activity of the enzymes in vivo. Bioelectromagnetics 24:449–456, 2003. © 2003 Wiley‐Liss, Inc.
Effects of ELF magnetic field on membrane protein structure of living HeLa cells studied by Fourier transform infrared spectroscopy
Authors: Ikehara Toshitaka , Yamaguchi Hisao , Hosokawa Keiko , Miyamoto Hiroshi , Aizawa Katsuo
Published: September 2003

The effects of exposure to a 50 Hz magnetic field (maximum of 41.7 to 43.6 mT) on the membrane protein structures of living HeLa cells were studied using attenuated total reflection infrared spectroscopy. One min of such exposure shifted peak absorbance of the amide I band to a smaller wave number, reduced peak absorbance of the amide II band, and increased absorbance at around 1600 cm−1. These results suggest that exposure to the ELF magnetic field has reversible effects on the N–H inplane bending and C–N stretching vibrations of peptide linkages, and changes the secondary structures of α‐helix and β‐sheet in cell membrane proteins. Bioelectromagnetics 24:457–464, 2003. © 2003 Wiley‐Liss, Inc.
Power line frequency electromagnetic fields do not increase the rate of protein synthesis in human skin fibroblasts as previously reported
Authors: Shi Biao , Isseroff R. Rivkah , Nuccitelli Richard
Published: September 2003

Rodemann et al. [Rodemann et al. (1987): Biochem Biophys Res Commun 145:1–9] reported that human skin fibroblasts increase their rate of protein synthesis by as much as over ninefold in response to long term exposure to 20 Hz, 8.4 mT (84 G) magnetic fields. Here we report studies of protein synthesis using an identical cell type, exposure conditions, and the same means of measuring protein synthetic rates. Our initial goal was to determine if the earlier results could be replicated, but we found an inconsistency in the earlier protocol. It exposed cells to [3H]leucine for 6 h prior to measuring incorporation into protein. We found, however, that 24 h is required for [3H]leucine to reach a steady state distribution across the cells' plasma membranes. In addition, we typically measured 100–200 cpm/thousand cells. This is four‐ to eightfold higher than the 19–28 cpm/1000 cells previously reported. Using these conditions, we could find no significant difference in protein synthesis rates between control cells and cells exposed for up to three weeks in an identical electromagnetic field. In addition, we investigated the effects of a 60 Hz field since that is the frequency used for electric power distribution in the United States. Again, we could find no significant effect of this field on rates of protein synthesis, even after 21 days of exposure. Bioelectromagnetics 24:465–472, 2003. © 2003 Wiley‐Liss, Inc.
Effect of a 125 mT static magnetic field on the kinetics of voltage activated Na+ channels in GH3 cells
Authors: Rosen Arthur D.
Published: September 2003

Voltage activated Na+ channels were examined in GH3 cells, using the whole cell patch clamp method. Channel currents were recorded before, during, and after a 150 s exposure to a 125 mT static magnetic field. There was a slight shift in the current–voltage relationship and a less than 5% reduction in peak current during magnetic field exposure. More pronounced, however, was an increase in the activation time constant, τm, during and for at least 100 s following exposure to the field. This change in τm was seen primarily at lower activation voltages. No change was noted in the inactivation time constant, τh. Changes were clearly temperature dependent, being evident only at and above 35 °C. These findings are consistent with the hypothesis that reorientation of diamagnetic anisotropic molecules in the cell membrane are capable of distorting imbedded ion channels sufficiently to alter their function. The temperature dependence of this phenomenon is probably due to the greater ease with which a liquid crystal membrane can be deformed. Bioelectromagnetics 24:517–523, 2003. © 2003 Wiley‐Liss, Inc.
RF nonlinear interactions in living cells–II: Detection methods for spectral signatures
Authors: Balzano Quirino
Published: September 2003

The presence of harmonic products due to possible nonlinear interaction of amplitude modulated RF signals in living cells is best detected by using a cavity with high quality factor. Harmonic products generated by elementary oscillators can be trapped and accumulated in a cavity, permitting detection sensitivity much greater than in an open environment, where they would be radiated in all directions. The experimental method described herein is a systematic approach to detection of the non‐Planck RF energy (if any) emitted by an exposed sample of living cells. Balzano and Sheppard [Balzano and Sheppard (2003): Bioelectromagnetics 24:473–482] classified the non‐Planck RF emissions from living cells as coming from (1) nonlinear interactions and (2) inelastic interactions. Nonlinear harmonic products would appear in the band at twice the frequency of an amplitude modulated RF carrier. Inelastic interaction products resulting from the interaction between the incident RF energy and normally occurring mechanical vibrations are found in the band immediately adjacent to the carrier. Detection of the latter signals is difficult because of this close spectral proximity, for example, 1 part in 107 for 100 Hz modulation of a GHz carrier. Modern audio spectrum analyzers have excellent selectivity, providing 60 dB rejections only 2 kHz away from the carrier. By judicious selection of the amplitude modulation (AM) frequency, frequency of the RF carrier, and size of the biological sample, it is possible to achieve very high sensitivity (about −90 dBm) with commercially available instrumentation. The presence (or absence) of harmonics in the band adjacent to the amplitude modulated RF carrier would establish (or negate) the existence of coherent interactions between mechanical vibrations in the cell ensemble and the incident RF signal. Bioelectromagnetics 24:483–488, 2003. © 2003 Wiley‐Liss, Inc.
RF nonlinear interactions in living cells–I: Nonequilibrium thermodynamic theory
Authors: Balzano Quirino , Sheppard Asher
Published: September 2003

Some biological experiments report effects that depend on low frequency modulation of a radiofrequency (RF) carrier. Such effects require nonlinear responses in biological preparations, which we show could be observed with great generality by the unique frequency signatures that would appear in the scattered RF energy. Following Illinger [Illinger (1982): Bioelectromagnetics 3:9–16], we considered a two part physical system. The greater part, dominated by the properties of water, interacts linearly with the RF field and is described by equilibrium thermodynamics. However, another, much smaller part, e.g., certain biological molecules and molecular subgroups, supports nonlinear interactions and is described by nonequilibrium thermodynamics. For example, a nonlinear interaction might result from scattering of RF photons from oscillators located in a region of strong field gradients, such as at membrane surfaces. A second nonlinear mechanism could appear if stress (elastic) waves were launched within the confines of the exposure vessel by RF heating. Amplitude modulation at angular frequency Ω of a carrier wave with angular frequency ω (Ω ≪ ω) produces two peaks in elastic stress in the cell structure during each period; that is, there is “full‐wave demodulation.” As a result of coherent nonlinear charge motion, modulation products could appear at frequencies ω ± 2Ω and, in general, at ω ± n 2Ω (n = 1, 2,…) if vibrational harmonics at 2 nΩ also are excited. Although in principle microwaves can alter the stability of a thermodynamic system by pumping a chemical transition, the degree of nonlinear coupling required for an observable instability is so great that its probability is effectively zero, unless field intensity is extremely high. A companion paper suggests an extremely sensitive method and the related instrumentation for detection of the spectrum scattered by living cells during exposure to amplitude modulated RF energy. Bioelectromagnetics 24:473–482, 2003. © 2003 Wiley‐Liss, Inc.