bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Structure Activity Relationships for Predicting the Bioaccumulation of POPs in Terrestrial Food‐Webs
Authors: Gobas Frank A. P. C. , Kelly Barry C. , Arnot Jon A.
Published: May 2003

KOW based QSARs are used to assess the bioaccumulation potential of thousands of commercial chemicals in Canada and internationally. The QSARs, which are based on information from aquatic organisms, identify chemicals with a log KOW>5 to have a potential to biomagnify in food‐chains. This study investigates whether KOW based QSARs are also effective in identifying biomagnifying chemicals in terrestrial food‐chains. First, a terrestrial bioaccumulation model is developed and used to hypothesize the general relationship between the chemical's octanol‐air and octanol‐water partition and its biomagnification potential. Secondly, field observations of the bioaccumulation of persistent organic pollutants in wolves are used to test the hypothesis and explore the fundamental differences between QSARs for bioaccumulation in aquatic and terrestrial food‐chains. The results indicate that (i) QSARs for bioaccumulation in terrestrial food‐chains should include both octanol‐air (KOA) and octanol water partition coefficients (KOW); (ii) chemicals with a log KOA>approximately 5 can biomagnify in terrestrial food‐chains if log KOW>2 and the rate chemical transformation or metabolism is low; (iii) biomagnification factors in terrestrial food‐chains are much greater than those in aquatic food‐chains; (iv) biomagnification factors of very hydrophobic substances (log KOW>7) in terrestrial biota do not drop off with increasing KOW as has been observed in aquatic biota. The relevance of these findings is that current regulations and protocols may misidentify (i) low KOW but high KOA chemicals as having no bioaccumulation potential and (ii) very hydrophobic (log KOW>8.5) which appear not to biomagnify in aquatic organisms but have the potential to biomagnify in terrestrial food‐chains. Considering that 67.9% of the approximately 12 000 organic chemicals on Canada's Domestic Substances List exhibit high KOA but low KOW, this represents a major gap in our methods for screening bioaccumulative substances.
A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs
Authors: Arnot Jon A. , Gobas Frank A. P. C.
Published: May 2003

This study presents the development of a quantitative‐structure activity relationship (QSAR) for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. The QSAR is derived by parameterization and calibration of a mechanistic food web bioaccumulation model. Calibration of the QSAR is based on the derivation of a large database of bioconcentration and bioaccumulation factors, which is evaluated for data quality. The QSAR provides estimates of the bioaccumulation potential of organic chemicals in higher trophic level fish species of aquatic food webs. The QSAR can be adapted to include the effect of metabolic transformation and trophic dilution on the BAF. The BAF‐QSAR can be applied to categorize organic chemical substances on their bioaccumulation potential. It identifies chemicals with a log KOW between 4.0 and 12.2 to exhibit BAFs greater than 5 000 in the absence of significant metabolic transformation rates. The BAF‐QSAR can also be used in the derivation of water quality guidelines and total maximum daily loadings by relating internal concentrations of organic chemicals in upper trophic fish species to corresponding concentrations in the water.
Improving Opportunities for Regulatory Acceptance of QSARs: The Importance of Model Domain, Uncertainty, Validity and Predictability
Authors: Walker John D. , Carlsen Lars , Jaworska Joanna
Published: May 2003

For Quantitative Structure Activity Relationships (QSARs) to be accepted by the regulated and regulatory communities, their scope for use needs to be agreed upon by government and industry. This paper discusses the importance of model domain, uncertainty, validity and predictability assessment in promoting the regulatory acceptance of QSARs.
Verification of literature‐derived SARs for skin irritation and corrosion
Authors: Hulzebos E. M. , Maslankiewicz L. , Walker J. D.
Published: May 2003

Structural features known to irritate and corrode skin and physical properties associated with skin absorption were used to evaluate the irritation and corrosion potential of chemicals. Chemicals that irritate and corrode skin include organic acids and bases, aldehydes, halogenated esters, and chemicals with reactive groups. The activity of the reactive group decreases when sterically hindered by adjacent substituents or when electrons of the reactive group interfere with electrons of adjacent substituents. The structural features presented are a good basis for the calculation of SAR prediction rules. Also quantitative and qualitative physical conditions are given to predict skin irritation and skin corrosion.
QSAR Prediction of Ozone Tropospheric Degradation
Authors: Gramatica Paola , Pilutti Pamela , Papa Ester
Published: May 2003

The lifetime of organic chemicals in the atmosphere can be calculated from a knowledge of the rate constant of their reaction with free radicals (OH., NO3.) and O3. The rate constant for the tropospheric degradation of 125 organic compounds by reaction with ozone, the least widely and successfully modelled degradation process, is predicted here by MLR‐QSAR modelling based on a variety of theoretical molecular descriptors, selected by the Genetic Algorithm‐Variable Subset Selection (GA‐VSS) procedure. The proposed models, checked for their reliability and robustness, have good predictivity, verified by internal (Q2LMO(50%)=82–88%) and also external validation (Q2EXT =90%). The best splitting of the original data set into representative training and test sets has been obtained by the Experimental Design approach. The model applicability domain was always verified by the leverage approach. The average root‐mean square error (RMS) for the prediction of log kO3 was 0.73, similar to the typical range of experimental error.
QSAR Modeling of Bioconcentration Factor by theoretical molecular descriptors
Authors: Gramatica Paola , Papa Ester
Published: May 2003

Bioconcentration factor (BCF) is an important ecotoxicological parameter describing the tendency of chemical concentration in organisms, mainly aquatic. Log BCF of 238 non‐ionic organic compounds was modelled by multiple linear regression models, using theoretical structural descriptors of different kinds (1D‐, 2D‐ and 3D‐) selected by the Genetic Algorithm procedure. The models, validated for their predictivity using internal (Q2, Q2LMO) and external validations (Q2EXT) can be applied for the prediction of not available data, and also for not yet synthesized compounds. Comparison of the proposed models and log Kow‐ or molecular connectivity (MCIs)‐based models reveals that our approach is more predictive than the log Kow‐based model and also simpler than the MCIs‐based model.
Using HPV Chemical Data to Develop QSARs for Non‐HPV Chemicals: Opportunities to Promote More Efficient Use of Chemical Testing Resources
Authors: Walker John D. , Dimitrov Sabcho , Mekenyan Ovanes
Published: May 2003

There are opportunities to use data developed for High Production Volume (HPV) chemicals to save chemical testing resources for non‐HPV chemicals. First, data being developed for HPV chemicals could reduce chemical testing resources for non‐HPV chemicals, if the data can be used to develop and validate Quantitative Structure Activity Relationships (QSARs) that can be used to make predictions for non‐HPV chemicals. Second, strategies need to be developed to identify chemicals for which QSARs may not make reliable predictions and appropriate tests need to be conducted so that these and related chemicals can be included in more robust QSAR predictions. This paper illustrates the chemical testing resources that could be saved by using QSAR predictions and discusses guidelines and issues that need to be addressed before using data from HPV chemicals to develop QSARs for non‐HPV chemicals.
Simple prediction of atmospheric concentration of hydrophilic compounds based on the classification of industrial uses
Authors: Kishi Hideko , Sekine Yoshika
Published: May 2003

Volatilization is a route of emission to an atmospheric compartment for chemicals. Although there are many good mathematical models for estimating the fate of volatile chemicals, agreement between the predicted and the measured concentration in air is not exactly evaluated because of the lack of emission factors and details on atmospheric chemistry. Moreover, available parameters are mostly limited for hydrophobic compounds. As a first step, authors investigated the relationship between annual production and atmospheric concentrations of volatile chemicals in the atmospheric monitoring data collected by the Ministry of Environment of Japan since 1974. Hydrophobic compounds were divided into two groups according to industrial uses: solvents/extraction agents and organic materials of chemical products. Significant linear regressions were found for both groups. The relationship between atmospheric concentrations of chemicals (Cair, ng/m3) against the amounts of annual production was expressed in logarithmic correlation equations; log Cair=1.32 log annual production −2.46, R2=0.70 and log Cair=0.72 log annual production −1.43, R2=0.92. The difference between the slopes may reflect emission factors of the processes. Then, these regression equations were applied to the 19 hydrophilic chemicals having OH, CHO, CO, COO, Oand (COOR)n inputting their annual production data. The predicted concentrations of such oxygenic compounds, if the industrial uses were determined, showed good agreement to the measured ones.
Pharmaceuticals and Personal Care Products in the Environment: Regulatory Drivers and Research Needs
Authors: Breton Roger , Boxall Alistair
Published: May 2003

The potential effect of human and veterinary medicines and other personal care products on the environment has become an important topic over the past few years. Whilst an assessment of the potential environmental risks posed by new and existing pharmaceuticals has been required in the United States (U.S.) for a number of decades, in the European Union (EU) and Canada assessments have only been required in the last 5–10 years. In the U.S., guidance has been available since the early 1980s on the assessment of veterinary medicines, whereas only recently has detailed guidance become available on how to perform the risk assessment in other areas. For example, in Canada, new pharmaceuticals (and other substances including novel foods, food additives, human biologics and genetic therapies, medical devices, natural health products, veterinary drugs, cosmetics) have been required to be notified for an environmental assessment under the Canadian Environmental Protection Act (CEPA 1999) since 2001. The European Medicines Evaluation Authority (EMEA) has published guidelines for assessment of veterinary medicines in use in Europe. For veterinary medicines attempts are currently being made by the Veterinary International Co‐operation on Harmonisation (VICH) to harmonise these approaches. Generally, the current assessment approaches are tiered and initially involve a comparison of environmental concentrations with set trigger values. If the trigger values are exceeded then a formal assessment has to be performed requiring data on environmental fate and ecotoxicity. Concerns have been raised over the current approaches used in each of the assessment processes and there are a number of areas that warrant further research. This paper will provide an overview of the regulatory assessment of pharmaceuticals and personal care products (PPCPs) and will expand on many of the topics for research in the future, and the role that QSAR scientists can play in this research will be highlighted.
Minimum binding energy and size of the doubly muonic T3 molecule
Authors: Eskandari M. R. , Faghihi F.
Published: May 2003

The minimum energy and size of doubly muonic T3 molecule in which two of the electrons are replaced by the much heavier muons are calculated by the well‐known variational method. The calculations show that the system possesses two minimum positions, one at a typically muonic distance and the second at the atomic distance. It is shown that at the muonic distance the effective charge, zeff, is 2.88. We assumed a symmetrical planar vibrational model between two minima and an oscillation potential energy is approximated in this region. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 377–383, 2003
Investigation of nucleoside analogs with anti‐HIV activity
Authors: Arissawa Márcia , Taft Carlton Anthony , Felcman Judith
Published: May 2003

Although a relatively large number of drugs that inhibit human immunodeficiency syndrome (HIV)‐1 reverse transcriptase have been developed—such as AZT, d4T, ddI, 3TC, and ddC, which are chain terminating nucleoside analogs—resistance is still a major problem. Atomic charges, regioselective patterns of chemical reactivity, and other indices of biochemical activity may help us acquire a better understanding of how the drugs work and the mechanism of drug resistance. In this work, we investigated the above‐mentioned nucleoside analogs using the ab initio Hartree–Fock method with 3‐21G, 3‐21G*, 6‐31G, 6‐31G*, 6‐31G**, and 6‐31+G** basis sets as well as B3LYP/6‐31G**, including thus diffusion, polarization, and correlation effects to obtain fully optimized geometric parameters. Vibrational frequencies were calculated and we also investigated the effects of solvents, Mulliken, and natural bond orbital charge distribution, as well as hydrogen bond effects. We tried to correlate very low and very high anti‐HIV activity with charges, vibrational stretching frequencies, interatomic distances, and the effect of solvents. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 422–432, 2003
Gelatinisation Characteristics of Cassava Starch Settled in the Presence of Different Chemicals
Authors: Sajeev Moothandassery S. , Moorthy Subramoni N. , Kailappan Ramasami , Rani Vijayalekshmi Sunitha
Published: May 2003

Addition of chemicals during the extraction of cassava starch for enhancing the settling rate, whiteness and compactness of the settled starch is an accepted commercial practice. The effect of addition of selected chemicals such as acids (sulphuric and hydrochloric acids), bleaching and oxidising agents (sodium metabisulphite and sodium hypochlorite) and alum during settling on the thermal and pasting properties of the cassava starch was examined. Treatment with sulphuric acid produced a noticeable increase in all DSC gelatinisation parameters, viz. onset gelatinisation temperature (To), temperature at peak minimum (Tp) and end temperature (Te), with increasing concentration of acid, while only a marginal shift could be obtained even at higher concentration of hydrochloric acid. However, no major effect resulted from treatment with sodium metabisulphite, sodium hypochlorite and alum. The gelatinisation enthalpy was hardly affected by the treatments. An exception was hydrochloric acid, which brought about a perceptible decrease in enthalpy at higher concentrations indicating that starch crystallinity is influenced to a small extent by hydrochloric acid. Pasting characteristics studied using a Rapid Visco Analyser showed that sulphuric acid, even at the lowest concentration (5 mM), considerably affected the structural characteristics of cassava starch, while hydrochloric acid induced similar effect only at higher concentrations. Alum reduced the paste viscosity while the bleaching agents (sodium metabisulphite and sodium hypochlorite) were not so effective in modifying the starch viscosity characteristics.
Cyclodextrins in the Textile Industry
Authors: Szejtli József
Published: May 2003

In the future cyclodextrins might play a significant role in the textile industry and might be used: (1) to remove surfactants from washed textiles; (2) to substitute surfactants; (3) in finishing textiles; (4) when bound chemically to fibers, to provide enhanced hydrophilicity and first of all, inclusion complex forming ability to immobilize perfumes, insect repellents, antimicrobial agents, etc.
Neurotoxic methamphetamine regimen severely impairs recognition memory in rats
Authors: Schröder Nadja , O'Dell Steven J. , Marshall John F.
Published: May 2003

Methamphetamine (mAMPH), when administered repeatedly to rodents or primates, is neurotoxic to some cortical neurons and to forebrain dopaminergic and serotonergic axon terminals. The aim of the present study was to investigate the effects of a neurotoxic regimen of mAMPH on two hippocampus‐dependent memory tasks: object recognition, a nonspatial memory task, and the Morris water maze, a spatial memory task. Male rats were treated with mAMPH (4 × 4.0 mg/kg, s.c.) or saline and trained in the object recognition task 1 week and 3 weeks later. During training, animals explored two identical copies of the same object. In retention test sessions one of the objects was replaced by a novel object. mAMPH‐treated rats showed no recognition memory during the short‐term memory (STM) test, given 90 min after the training session, and showed marked impairments in the long‐term memory (LTM) test, given 24 h after training. Even 3 weeks after drug injections, the mAMPH‐treated animals were unable to discriminate between the novel and familiar objects during both STM and LTM tests. Despite the severe deficits observed in the recognition memory, no effects of prior mAMPH treatment were seen in the water maze task. Damage to monoamine terminals was confirmed by significant 30–40% losses of [125I]RTI‐55 binding to striatal dopamine transporter and hippocampal serotonin transporter sites at both 1 and 3 weeks after mAMPH treatments. Thus, administration of mAMPH restricted to a single day can produce a profound, persistent, and selective deficit in a nonspatial hippocampus‐dependent memory. Synapse 49:89–96, 2003. © 2003 Wiley‐Liss, Inc.
Blockade of neuronal facilitatory nicotinic receptors containing α3β2 subunits contribute to tetanic fade in the rat isolated diaphragm
Authors: Faria Miguel , Oliveira Laura , Timóteo M. Alexandrina , Lobo M. Graça , Correia‐de‐sá Paulo
Published: May 2003

Nicotinic receptor (nAChR) subtypes involved in pre‐ and postjunctional actions underlying tetanic fade were studied in rat phrenic‐nerve hemidiaphragms. We investigated the ability of subtype‐specific nAChR antagonists to depress nerve‐evoked contractions and [3H]‐acetylcholine ([3H]‐ACh) release. Muscle tension was transiently increased during brief high frequency trains (50 Hz for 5 sec). The rank potency order of nAChR antagonists to reduce tetanic peak tension was α‐bungarotoxin > d‐tubocurarine ≫ mecamylamine > hexamethonium. Reduction of maximal tetanic tension produced by dihydro‐β‐erythroidine (0.03–10 μM), methyllycaconitine (0.003–3 μM), and α‐conotoxin MII (0.001–0.3 μM) did not exceed 30%. Besides reduction of peak tension d‐tubocurarine (0.1–0.7 μM), mecamylamine (0.1–300 μM), and hexamethonium (30–3,000 μM) also caused tetanic fading. With α‐conotoxin MII (0.001–0.3 μM) and dihydro‐β‐erythroidine (0.03–10 μM), tetanic fade was evident only after decreasing the safety factor of neuromuscular transmission (with high magnesium ions, 6–7 mM). The antagonist rank potency order to reduce evoked (50 Hz for 5 sec) [3H]‐ACh release from motor nerve terminals was α‐conotoxin MII (0.1 μM) > dihydro‐β‐erythroidine (1 μM) ∼ d‐tubocurarine (1 μM) > mecamylamine (100 μM) > hexamethonium (1,000 μM). When applied in a concentration (0.3 μM) above that producing tetanic paralysis, α‐bungarotoxin failed to affect [3H]‐ACh release. Data obtained suggest that postjunctional neuromuscular relaxants interact with α‐bungarotoxin‐sensitive nicotinic receptors containing α1‐subunits, whereas blockade of neuronal α3β2‐containing receptors produce tetanic fade by breaking nicotinic autofacilitation of acetylcholine release. Synapse 49:77–88, 2003. © 2003 Wiley‐Liss, Inc.
Monocarboxylate transporters contribute to the adaptation of neuronal activity to repeated glucose deprivation in the rat lateral septal nucleus
Authors: Hasuo Hiroshi , Akasu Takashi
Published: May 2003

Using optical recording methods in the rat lateral septal nucleus (LSN) slice, we examined the question of whether antecedent hypoglycemia protects neurons from the adverse effects of subsequent hypoglycemic stimuli. The first exposure of LSN neurons to glucose deprivation for 15 min produced a marked depression of neuronal activity. The neuronal activity recovered by reapplication of glucose to the neurons. In neurons previously exposed to glucose deprivation, subsequent applications of glucose‐free artificial cerebrospinal fluid (ACSF) produced only weak depression of the neuronal activity. The contribution of monocarboxylate transporters to this adaptation of neuronal activity to repeated glucose deprivation was examined in LSN neurons. α‐Cyano‐4‐hydroxycinnamate (4‐CIN, 100 μM), an inhibitor of the monocarboxylate transporters, did not significantly affect the depression of the neuronal activity induced by the first glucose deprivation. However, in the presence of 4‐CIN (100 μM), a second glucose deprivation produced a typical depression of the neuronal activity, indicating that 4‐CIN had nullified the adaptation of neuronal activity to a second glucose deprivation. Cytochalasin B (CCB, 20 μM), an inhibitor of glucose transporters, depressed the neuronal activity in the presence of 11 mM glucose. Pyruvate (11 mM) partially restored the neuronal activity depressed by pretreatment with CCB (20 μM) for 30–40 min. These results suggest that antecedent glucose deprivation stimulates monocarboxylate‐transporters to supply energy substrates to LSN neurons, thus protecting the neurons against subsequent glucose deprivation. Synapse 49:97–105, 2003. © 2003 Wiley‐Liss, Inc.
Changes in NPY‐mediated modulation of hippocampal [3H]D‐aspartate outflow in the kindling model of epilepsy
Authors: Rodi Donata , Mazzuferi Manuela , Bregola Gianni , Dumont Yvan , Fournier Alain , Quirion Remi , Simonato Michele
Published: May 2003

The anticonvulsant effect of NPY may depend on Y2 and/or Y5 receptor‐mediated inhibition of glutamate release in critical areas, such as the hippocampus. However, Y2 and Y5 receptor levels have been reported to increase and decrease, respectively, in the epileptic hippocampus, implicating that the profile of NPY effects may change accordingly. The aim of this study was to evaluate the differential effects of NPY on glutamate release in the normal and in the epileptic hippocampus. Thus, we pharmacologically characterized the effects of NPY on the release of [3H]D‐aspartate, a valid marker of endogenous glutamate, from synaptosomes prepared from the whole hippocampus and from the three hippocampal subregions (dentate gyrus and CA1 and CA3 subfields) of control and kindled rats, killed 1 week after the last stimulus‐evoked seizure. In the whole hippocampus, NPY does not significantly affect stimulus‐evoked [3H]D‐aspartate overflow. In synaptosomes prepared from control rats, NPY significantly inhibited 15 mM K+‐evoked [3H]D‐aspartate overflow only in the CA1 subfield (approx. −30%). Both Y2 and Y5 receptor antagonists (respectively, 1 μM BIIE0246 and 1 μM CGP71683A) prevented this effect, suggesting the involvement of both receptor types. In contrast, in synaptosomes prepared from kindled rats NPY significantly inhibited 15 mM K+‐evoked [3H]D‐aspartate overflow in the CA1 subfield and in the dentate gyrus (approx. –30%). Only the Y2 (not the Y5) antagonist prevented these effects. These data indicate a critical role for the Y2 receptor in the inhibitory control of glutamate release in the kindled hippocampus and, thus, suggest that the anticonvulsant effect of NPY in the epileptic brain is most likely Y2, but not Y5, receptor‐mediated. Synapse 49:116–124, 2003. © 2003 Wiley‐Liss, Inc.
Sensitivities of benzodiazepine receptor binding and muscarinic acetylcholine receptor binding for the detection of neural cell death caused by sodium nitroprusside microinjection in rat brain
Authors: Inoue Osamu , Yanamoto Kazuhiko , Fujiwara Yoshiko , Hosoi Rie , Kobayashi Kaoru , Tsukada Hideo
Published: May 2003

Sodium nitroprusside (SNP) was microinjected into rat cerebral cortex and changes in muscarinic acetylcholine receptor (mAChR) binding and benzodiazepine receptor (BZR) binding were followed for 24 h after the infusion using [3H]‐N‐methyl‐4‐piperidyl benzilate ([3H]‐NMPB) and [3H]‐flumazenil, respectively, as a radioligand. The microinjection of SNP dose‐dependently caused significant neural cell death 3 h after infusion, with the area of cell death becoming extensive 24 h after infusion. Neither SIN‐1 nor NOC‐18, other types of NO donors, caused neural cell death. Together with the result that deferoxamine, an iron‐chelating agent, protected SNP‐induced brain injury indicated important roles of iron‐related radicals in SNP cytotoxicity in rat brain. In vitro [3H]‐NMPB binding was significantly reduced in parallel with the time course of neural cell death detected by TTC staining and Nissl staining. In contrast, [3H]‐flumazenil binding was essentially unaltered during the 24‐h period after the SNP infusion. Similar results were observed in in vivo binding experiments. In vivo [3H]‐NMPB binding was found to be much more sensitive at detecting cell death caused by SNP. On the other hand, [3H]‐flumazenil binding in vivo was relatively insensitive to SNP‐induced cell death. These results indicate that mAChR binding may be superior to BZR binding for detecting cell death in brain tissue, in contrast to what was previously thought. Synapse 49:134–141, 2003. © 2003 Wiley‐Liss, Inc.
Role for calbindin‐D28K in in vitro classical conditioning of abducens nerve responses in turtles
Authors: Keifer Joyce , Brewer Boone T. , Meehan Phillip E. , Brue Richard J. , Clark Timothy G.
Published: May 2003

Intracellular calcium has a pivotal role in synaptic modifications that may underlie learning and memory. The present study examined whether there were changes in immunoreactivity levels of the AMPA receptor subunits GluR2/3 and calcium binding proteins during classical conditioning recorded in the abducens nerve of in vitro brain stem preparations from turtles. The results showed that abducens motor neurons in unconditioned turtle brain stems were immunopositive for GluR2/3, calbindin‐D28K, and calmodulin, but were immunonegative for parvalbumin. After classical conditioning, immunoreactivity for calbindin‐D28K in the abducens motor nuclei was significantly reduced, whereas there were no significant changes in GluR2/3, calmodulin, or parvalbumin. This reduction in calbindin‐D28K immunoreactivity was not observed following conditioning in the NMDA receptor antagonist AP‐5, which blocked conditioned responses, suggesting that these changes are NMDA receptor‐dependent. Moreover, the degree of the decrease in calbindin‐D28K immunoreactivity was negatively correlated with the level of conditioning. Consistent with the immunocytochemical findings, Western blot analysis showed that calbindin‐D28K protein levels were reduced after classical conditioning. The results support the hypothesis that in vitro classical conditioning of abducens nerve responses utilizes intracellular calcium‐dependent signaling pathways that require NMDA receptor function and suggest a specific role for the calcium binding protein calbindin‐D28K. Synapse 49:106–115, 2003. © 2003 Wiley‐Liss, Inc.
Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes
Authors: Giambalvo Cecilia T.
Published: May 2003

Amphetamine has been shown to increase striatal particulate protein kinase C (PKC) activity [Giambalvo (1992b) Neuropharmacology 31:1211–1222]. The present study examined possible mechanisms involved. Specifically, the effects of calcium, endogenous DA, and DA receptors on the amphetamine‐induced increase in PKC activity in striatal synaptoneurosomes were examined. Naïve rats and rats pretreated with N‐ethoxy‐carbonyl‐2‐ethoxy‐1,2‐dihydroquinolone (EEDQ, i.p.), a nonselective irreversible receptor antagonist, or with α‐methyl‐p‐tyrosine (AMPT, i.p.), a DA synthesis inhibitor, were sacrificed and striatal synaptoneurosomes were prepared. The tissue was incubated with amphetamine, with and without calcium, and PKC activity was then determined by the endogenous phosphorylation of endogenous substrate proteins, as described previously [Giambalvo (1988a) Biochem Pharmacol 37:4001–4007]. It was found that calcium enhanced the effect of amphetamine on PKC activity, even in rats pretreated with EEDQ. Intracellular calcium was required since pretreatment with 1,2‐bis (2‐aminophenoxy) ethane‐N, N, N, N‐tetracetic acid acetoxymethyl ester (BAPTA‐AM) in vitro attenuated the amphetamine‐induced increase in PKC activity, resulting in an inhibition of PKC activity instead. Likewise, endogenous DA was essential since pretreatment with AMPT resulted in a similar amphetamine‐induced inhibition of PKC activity. Pretreatment with AMPT did not alter the inhibitory effect of the D2 DA agonist, LY 171555, on PKC activity. It did, however, abolish the calcium‐dependent stimulatory effect of the D1 agonist SKF 38393 on PKC activity, rendering it inhibitory regardless of calcium. Considering that both BAPTA‐AM and AMPT pretreatments, which diminished DA release without affecting uptake via different mechanisms, produced similar inhibitory effects on PKC activity by amphetamine, these results suggest that the inward transport of amphetamine had an inhibitory effect on PKC activity. In contrast, the outward transport of DA seemed to have a stimulatory effect on PKC activity since incubation with low sodium or with ouabain, conditions that promote DA reverse‐transport, increased PKC activity. These results showed that PKC activity was altered differently during inward vs. outward transport. The amphetamine‐induced increase in PKC activity was attenuated by pretreatment with DA uptake blockers (nomifensine, GBR 12935, and bupropion), even though these drugs by themselves also increased PKC activity. This effect was diminished by calcium and persisted in rats pretreated with EEDQ. Thus, calcium had a differential effect on the PKC activity induced by a transported substrate (amphetamine) vs. nontransported inhibitors (DA uptake blockers). Synapse 49:125–133, 2003. © 2003 Wiley‐Liss, Inc.
Microbiological evaluation of toxicity of three polycyclic aromatic hydrocarbons and their decomposition products formed by advanced oxidation processes
Authors: Jamroz Teresa , Ledakowicz Stanisław , Miller Jacek S. , Sencio Barbara
Published: May 2003

The toxicity of benzo[a]pyrene, chrysene, and fluorene and their decomposition products formed by advanced oxidation processes (AOPs) was investigated using biotests with Escherichia coli and Vibrio fischeri. The polycyclic aromatic hydrocarbons (PAHs) were not highly toxic to either bacterial strain; the toxicity of their degradation products depended on the method of chemical processing. Inhibition of more than 27% was observed with products formed by oxidation of the PAHs, by AOP methods without hydrogen peroxide. Toxicity as high as 100% was observed after the combined action of hydrogen peroxide and other oxidizing agents. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 187–191, 2003
Review: Environmental exposure to mercury and its toxicopathologic implications for public health
Authors: Tchounwou Paul B. , Ayensu Wellington K. , Ninashvili Nanuli , Sutton Dwayne
Published: May 2003

Mercury is a toxic and hazardous metal that occurs naturally in the earth's crust. Natural phenomena such as erosion and volcanic eruptions, and anthropogenic activities like metal smelting and industrial production and use may lead to substantial contamination of the environment with mercury. Through consumption of mercury in food, the populations of many areas, particularly in the developing world, have been confronted with catastrophic outbreaks of mercury‐induced diseases and mortality. Countries such as Japan, Iraq, Ghana, the Seychelles, and the Faroe Islands have faced such epidemics, which have unraveled the insidious and debilitating nature of mercury poisoning. Its creeping neurotoxicity is highly devastating, particularly in the central and peripheral nervous systems of children. Central nervous system defects and erethism as well as arrythmias, cardiomyopathies, and kidney damage have been associated with mercury exposure. Necrotizing bronchitis and pneumonitis arising from inhalation of mercury vapor can result in respiratory failure. Mercury is also considered a potent immunostimulant and ‐suppressant, depending on exposure dose and individual susceptibility, producing a number of pathologic sequelae including lymphoproliferation, hypergammaglobulinemia, and total systemic hyper‐ and hyporeactivities. In this review we discuss the sources of mercury and the potential for human exposure; its biogeochemical cycling in the environment; its systemic, immunotoxic, genotoxic/carcinogenic, and teratogenic health effects; and the dietary influences on its toxicity; as well as the important considerations in risk assessment and management of mercury poisoning. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 149–175, 2003.
Gene regulation in response to protein disulphide isomerase deficiency
Authors: Nørgaard Per , Tachibana Christine , Bruun Anette W. , Winther Jakob R.
Published: May 2003

We have examined the activities of promoters of a number of yeast genes encoding resident endoplasmic reticulum proteins, and found increased expression in a strain with severe protein disulphide isomerase deficiency. Serial deletion in the promoter of the MPD1 gene, which encodes a PDI1‐homologue, revealed a cis‐acting element responding to deficiency of protein disulphide isomerase activity (designated CERP). The presence of the sequence element is necessary and sufficient for the upregulation in response to disulphide isomerase deficiency, as measured by a minimal promoter containing the CERP element. The sequence (GACACG) does not resemble the unfolded protein response element. It is present in the upstream regions of the MPD1, MPD2, KAR2, PDI1 and ERO1 genes. Copyright © 2003 John Wiley & Sons, Ltd.
Moderately lipophilic carboxylate compounds are the selective inducers of the Saccharomyces cerevisiae Pdr12p ATP‐binding cassette transporter
Authors: Hatzixanthis Kostas , Mollapour Mehdi , Seymour Ian , Bauer Bettina E. , Krapf Gerd , Schüller Christoph , Kuchler Karl , Piper Peter W.
Published: May 2003

Saccharomyces cerevisiae displays very strong induction of a single ATP‐binding cassette (ABC) transporter, Pdr12p, when stressed with certain weak organic acids. This is a plasma membrane pump catalysing active efflux of the organic acid anion from the cell. Pdr12p action probably allows S. cerevisiae to maintain lower intracellular levels of several weak organic acid preservatives than would be expected on the basis of the free equilibration of the acid across the cell membrane. This in turn facilitates growth in the presence of these preservatives and therefore yeast spoilage of food materials. Pdr12p appears to confer resistance to those carboxylic acids that, to a reasonable degree, partition into both the lipid bilayer and aqueous phases. Its gene (PDR12) is strongly induced by sorbate, benzoate and certain other moderately lipophilic carboxylate compounds, but not by organic alcohols or high levels of acetate. PDR12 induction reflects the operation of a previously uncharacterized S. cerevisiae stress response, for which the induction signal is probably a high intracellular pool of the organic acid anion. Copyright © 2003 John Wiley & Sons, Ltd.
A ‘marker switch’ approach for targeted mutagenesis of genes in Schizosaccharomyces pombe
Authors: MacIver Fiona H. , Glover David. M. , Hagan Iain M.
Published: May 2003

The completion of the Schizosaccharomyces pombe genome sequencing project has led to a dramatic acceleration of gene characterization in this system. Once a gene has been identified, the challenge then comes in using reverse genetics to generate a range of mutants in this gene of interest so that the powerful genetics and wealth of genetic backgrounds available in Sz. pombe can be exploited to study the function of the newly identified molecule. Beyond simple PCR‐tagging approaches, the high frequency with which illegitimate recombination occurs in Sz. pombe has made the manipulation of some loci complex, time consuming and a process of trial and error. Here we describe a simple ‘marker switch’ approach that enables the rapid selection of integration events at the locus of interest from an excessive background of integration at heterologous sites. We use the generation of temperature‐sensitive mutations in the plo1+ gene to validate this approach. Copyright © 2003 John Wiley & Sons, Ltd.
An analysis of the Candida albicans genome database for soluble secreted proteins using computer‐based prediction algorithms
Authors: Lee Samuel A. , Wormsley Steven , Kamoun Sophien , Lee Austin F. S. , Joiner Keith , Wong Brian
Published: May 2003

We sought to identify all genes in the Candida albicans genome database whose deduced proteins would likely be soluble secreted proteins (the secretome). While certain C. albicans secretory proteins have been studied in detail, more data on the entire secretome is needed. One approach to rapidly predict the functions of an entire proteome is to utilize genomic database information and prediction algorithms. Thus, we used a set of prediction algorithms to computationally define a potential C. albicans secretome. We first assembled a validation set of 47 C. albicans proteins that are known to be secreted and 47 that are known not to be secreted. The presence or absence of an N‐terminal signal peptide was correctly predicted by SignalP version 2.0 in 47 of 47 known secreted proteins and in 47 of 47 known non‐secreted proteins. When all 6165 C. albicans ORFs from CandidaDB were analysed with SignalP, 495 ORFs were predicted to encode proteins with N‐terminal signal peptides. In the set of 495 deduced proteins with N‐terminal signal peptides, 350 were predicted to have no transmembrane domains (or a single transmembrane domain at the extreme N‐terminus) and 300 of these were predicted not to be GPI‐anchored. TargetP was used to eliminate proteins with mitochondrial targeting signals, and the final computationally‐predicted C. albicans secretome was estimated to consist of up to 283 ORFs. The C. albicans secretome database is available at http://info.med.yale.edu/intmed/infdis/candida/ Copyright © 2003 John Wiley & Sons, Ltd.
KlROM2 encodes an essential GEF homologuein Kluyveromyces lactis
Authors: Lorberg Anja , Schmitz Hans‐Peter , Gengenbacher Ute , Heinisch Jürgen J.
Published: May 2003

Cellular integrity in yeasts is ensured by a rigid cell wall whose synthesis is controlled by a MAP kinase signal transduction cascade. In Saccharomyces cerevisiae upstream regulatory components of this MAP kinase pathway involve a single protein kinase C, which is regulated in part by interaction with the small GTPase Rho1p. This small G protein is in turn rendered inactive (GDP‐bound) or is activated (GTP‐bound) by the influence of GTPase activating proteins (GAPs) and the GDP/GTP exchange factors (GEFs), respectively. We report here on the isolation of a gene from Kluyveromyces lactis, KlROM2, which encodes a member of the latter protein family. The nucleotide sequence contains an open reading frame of 1227 amino acids, with an overall identity of 57% to the Rom2 protein of S. cerevisiae. Four conserved sequence motifs could be identified: a RhoGEF domain, a DEP sequence, a CNH domain and a less conserved pleckstrin homology (PH) sequence. Klrom2 null mutants show a lethal phenotype, which indicates that the gene may encode the only functional GEF regulating the cellular integrity pathway in K. lactis. Conditional genomic expression of KlROM2 resulted in sensitivity towards caffeine and Calcofluor white as typical phenotypes of mutants defective in this pathway. Overexpression of KlROM2 from multicopy plasmids under the control of the ScGAL1 promoter severely impaired growth in both S. cerevisiae and in K. lactis. The fact that the lethal phenotype was not prevented in mpk1 deletion mutants indicates that growth inhibition is not simply caused by hyperactivation of the Pkc1p signal transduction pathway. The GeneBank Accession No. for KlROM2 is AF421953. Copyright © 2003 John Wiley & Sons, Ltd.
Isolation of the MNN9 gene of Yarrowia lipolytica (YlMNN9) and phenotype analysis of a mutant ylmnn9Δ strain
Authors: Jaafar Lahcen , León Maela , Zueco Jesús
Published: May 2003

In this work we describe the isolation of the Yarrowia lipolytica homologue of Saccharomyces cerevisiae MNN9 gene, which we have named YlMNN9, and the phenotype analysis of a Y. lipolytica strain containing the disrupted YlMNN9 allele. YlMNN9 was cloned using degenerate consensus oligonucleotides to generate specific probes that were in turn used to screen mini‐gene libraries. The gene is defined by a 1014 bp ORF predicted to encode a protein 337 amino acids long that shares significant homology with the Mnn9ps of S. cerevisiae, Candida albicans and Hansenula polymorpha, including a putative N‐terminal transmembrane domain. Disruption of YlMNN9 leads to phenotypes such as resistance to sodium orthovanadate and sensitivity to hygromycin B, compatible with a glycosylation defect, and hypersensitivity to Calcofluor white, Congo red or zymolyase, characteristic of cell wall defects. Analysis of cell wall proteins present in β‐mercaptoethanol and zymolyase extracts showed significant differences between the parental and the ylmnn9Δ strain. These results suggest that, as has been the case with the mnn9 strain of S. cerevisiae, the ylmnn9Δ strain we present in this work, could be used to study the cell wall proteins of Y. lipolytica and how they are organized into the cell wall. The complete YlMNN9 sequence is available from GenBank under Accession No. AF441127. Copyright © 2003 John Wiley & Sons, Ltd.
Normierung und Evaluation der deutschen Elternversion des Strengths and Difficulties Questionnaire (SDQ): Ergebnisse einer repräsentativen Felderhebung
Authors: Woerner W. , Becker A. , Friedrich C. , Rothenberger A. , Klasen H. , Goodman R.
Published: May 2003

Zusammenfassung: Fragestellung: Der Strengths and Difficulties Questionnaire (SDQ) ist ein kurzer Fragebogen zu Verhaltensauffälligkeiten und -stärken bei Kindern und Jugendlichen, der in Eltern- und Lehrerversionen sowie als Selbstbericht vorliegt. Bei der Formulierung der 25 SDQ-Items wurde gezielt auf eine Ausgewogenheit von positiven und negativen Verhaltensaspekten geachtet. Zur deutschen Version existieren erste Validierungsbefunde, bislang aber noch keine Normierung. Methode: In einer bundesweiten repräsentativen Felderhebung wurde für 930 sechs- bis 16-jährige Kinder und Jugendliche die Elternversion des SDQ komplett ausgefüllt. Nach einer Überprüfung der faktoriellen Struktur der deutschen Fassung wurden anhand der Verteilungen der Skalenrohwerte Grenzwerte bestimmt, um individuelle Skalenwerte zu einer von drei Kategorien (unauffällig / Grenzbefund / auffällig) zuzuordnen. Schließlich wurden mögliche Geschlechts-, Alters- und Schichteffekte betrachtet. Ergebnisse: Die erhaltene faktorielle Struktur entsprach genau der ursprünglichen Skalenbildung. Statistisch bedeutsame, aber nur gering ausgeprägte Effekte von Alter, Geschlecht und sozialer Schichtzugehörigkeit führten lediglich beim Gesamtproblemwert zu einer differenzierten Bestimmung alters- und geschlechtsspezifischer Grenzwerte, nicht jedoch bei den SDQ-Einzelskalen. Schlussfolgerungen: Angesichts der exakten Replikation der 5 SDQ-Skalen erhöhen die hier erhobenen Normdaten den diagnostischen Wert des Instruments. Sie dienen ferner als Grundlage für weitere Validierungsstudien, um den klinischen Nutzen des deutschen SDQ als praktikables und ökonomisches Screening-Instrument, für die Eingangsdiagnostik sowie zur Dokumentation von Therapieverläufen zu evaluieren.
Definitionsmöglichkeiten und sich daraus ergebende Häufigkeit der umschriebenen Lese- bzw. Rechtschreibstörung - theoretische Überlegungen und empirische Befunde an einer repräsentativen Stichprobe junger Erwachsener
Authors: Strehlow U. , Haffner J.
Published: May 2003

Zusammenfassung: Fragestellung: An einer epidemiologischen Stichprobe Jugendlicher und junger Erwachsener wird die Bedeutung verschiedener Definitionsansätze zur umschriebenen Lese- bzw. Rechtschreibstörung dargestellt und diskutiert. Methode: Durch Anwendung am gleichen Datensatz wird untersucht, wie sich unterschiedliche Modelle, Definitionen und methodische Vorgehensweisen auf die empirischen und theoretisch zu erwartenden Fallhäufigkeiten der Rechtschreibschwäche auswirken. Die praktische Bedeutung verschiedener normorientierter Falldefinitionen wird anhand inhaltlicher Überlegungen und empirischer Außenkriterien beurteilt. Ergebnis: An inhaltlichen Kriterien orientierte Falldefinitionen führen in der vorliegenden Studie zu Prävalenzzahlen zwischen 6 bis 9%.
Theodor Ziehen als Kinder- und Jugendpsychiater. Eine verspätete Reminiszenz zum 50. Todestag
Authors: Gerhard U.-J. , Blanz B.
Published: May 2003

Zusammenfassung: Einleitung: Am 29. Dezember 2000 jährte sich zum 50. Mal der Todestag von Theodor Ziehen. Da dieses Ereignis kaum eine Würdigung fand, wird in dem vorliegenden Artikel insbesondere an seine Bedeutung als Kinder- und Jugendpsychiater erinnert. Methodik: Anhand von Literaturstudien erfolgt ein kurzer Abriss seines Lebens und die Wertung seines wissenschaftlichen Werkes. Schlussfolgerung: Ziehen (1862-1950) war ein äußerst vielseitiger Gelehrter. Bleibende Spuren hinterließ er nicht nur als Nervenarzt, sondern auch als Psychologe und Philosoph. Darüber hinaus zählt er zu den Gründervätern des Fachgebiets Kinder- und Jugendpsychiatrie. Die ersten entwicklungspsychologischen Untersuchungen, die 1898 in die Schrift «Die Ideenassoziation des Kindes» einflossen, unternahm er in Jena. Er arbeitete eng mit den Pädagogen Rein und Trüper zusammen. Im Jahr 1902 erschien der erste Teil des Buches «Die Geisteskrankheiten des Kindesalters», dem 1904 und 1906 weitere Teile folgten. Es dürfte sich um das zweite bedeutende deutschsprachige kinderpsychiatrische Werk handeln. Damit gelang es ihm, das erste systematische und weitgehend vollständige Lehrbuch der Kinderpsychiatrie herauszugeben. Er führte die Termini «Affektive Psychose» und «Psychopathische Konstitution» in die psychiatrische Nomenklatur ein. Auch auf dem Gebiet der Heilpädagogik und Pädagogik war Ziehen tätig.
Symptom oder Krankheit? Der erschöpfende Weg eines Jugendlichen mit chronischer Müdigkeit
Authors: Di Gallo A.
Published: May 2003

Zusammenfassung: Dieser Fallbericht stellt die Diagnostik bei einem 16-jährigen Jugendlichen mit einem chronischer Erschöpfungssyndrom (chronic fatigue syndrome, CFS) vor. Fragen zur Ätiologie, Dynamik, Diagnostik und Behandlung dieses komplexen Zustandsbildes werden kurz diskutiert.