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PubMed2004

Dysregulation of gene expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse substantia nigra.

Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2026

PathMED: an R toolkit for single-sample molecular scoring and machine learning with omics data.

MOTIVATION: Molecular scoring is a popular approach for studying pathway-level functional alterations with omics data. Using molecular scores for tasks such as single-sample molecular characterisation, phenotype prediction or disease stratification has several advantages compared to using omics data directly. Molecular scores provide biological interpretability and are more generalisable across datasets, facilitating data integration and machine learning applications. However, numerous scoring methods are available through different software packages, and currently there is a lack of tools to easily use these scores for model training and prediction. RESULTS: We developed pathMED, an R/Bioconductor package that unifies various scoring methods in a simple framework. Furthermore, pathMED also contains a machine learning module to train and test models that use the calculated molecular scores to predict clinical outcomes. We demonstrate some of its potential applications in three use cases using public omics data. We showed the generalisability of machine learning models trained on transcriptomic scores in predicting clinical outcomes when deploying on proteomic scores. We also demonstrated the application of transcriptomics scores in predicting breast cancer treatment response and identifying pathways strongly associated to tumour biology and treatment response. Finally, we demonstrated the benefit of integrating a novel gene set dissection step into the analysis pipeline to resolve disease heterogeneity at the pathway level. AVAILABILITY: PathMED is freely available in the Bioconductor repository (https://bioconductor.org/packages/release/bioc/html/pathMED.html). Code to reproduce the analyses is publicly available at https://github.com/GENyO-BioInformatics/pathMED_article.

Software↗

PubMed1997

[Requirements for a teleradiology system. Experiences with the MEDICUS-2 field test].

During the Medicus field test we gained experience using the teleradiology system for almost daily teleconferences between a radiology department and clinics for internal medicine, urology, and gynecology. The existing system has a high degree of functionality. The full 12-bit data format is available using the DICOM protocol. A data security concept is implemented, ensuring data integrity, privacy and authentication of communication partners. This concept covers the areas of organization, technique, user training, and software implementation. A future system should be a general purpose radiology workstation covering viewing functionality, image manipulation, and digital archive access. Dedicated teleradiology features have to be a part. Specialized evaluation software, e.g. for dynamic MRI, should be integratable in a modular way. For data exchange with other systems and for the synchronization of teleconference sessions, the protocols should be independent of the network standard used (ISDN, Ethernet, ATM) and based on the DICOM protocol. Extensions of the existing standard are therefore necessary. Besides future technical developments, reimbursement for teleradiology must be accomplished.

Computer Communication Networks↗

PubMed2004

Common denominator genes that distinguish colorectal carcinoma from normal mucosa.

PURPOSE: Microarray technology has been used by a growing number of investigators and several studies have been published that list hundreds of genes differentially expressed by colorectal carcinoma (CRC) and normal mucosa (MC). On the basis of our own and other investigators' microarray data, our goal was to identify a common denominator gene cluster distinguishing CRC from MC. METHODS: Thirty GeneChips (HG-U133A, Affymetrix) were hybridized, 20 with RNA of CRC stages I-IV (UICC) and 10 with MC. Expression signals showing at least a 4-fold difference between CRC and MC (p<0.01) were identified as differentially expressed. In addition, in our integrative data analysis approach only those genes whose expression was altered simultaneously in at least 2 of 5 recently published studies were subjected to an unsupervised hierarchical cluster analysis. RESULTS: We detected 168 up- and 283 down-regulated genes in CRC relative to MC. Twenty-three genes were filtered from the five articles reviewed. An unsupervised hierarchical cluster analysis of these 23 genes confirmed the high specificity of these genes to differentiate between CRC and MC in our microarray data. CONCLUSIONS: Colorectal cancer and mucosa could be clearly separated by 23 genes selected for being differentially expressed more than once in a recent literature review. These genes represent a common denominator gene cluster that can be used to distinguish colorectal MC from CRC.

Carcinoma↗

PubMed1999

EpoDB: a prototype database for the analysis of genes expressed during vertebrate erythropoiesis.

EpoDB is a database of genes expressed in vertebrate red blood cells. It is also a prototype for the creation of cell and tissue-specific databases from multiple external sources. The information in EpoDB obtained from GenBank, SWISS-PROT, Transfac, TRRD and GERD is curated to provide high quality data for sequence analysis aimed at understanding gene regulation during erythropoiesis. New protocols have been developed for data integration and updating entries. Using a BLAST-based algorithm, we have grouped GenBank entries representing the same gene together. This sequence similarity protocol was also used to identify new entries to be included in EpoDB. We have recently implemented our database in Sybase (relational tables) in addition to SICStus Prolog to provide us with greater flexibility in asking complex queries that utilize information from multiple sources. New additions to the public web site (http://www.cbil.upenn.edu/epodb) for accessing EpoDB are the ability to retrieve groups of entries representing different variants of the same gene and to retrieve gene expression data. The BLAST query has been enhanced by incorporating BLASTView, an interactive and graphical display of BLAST results. We have also enhanced the queries for retrieving sequence from specified genes by the addition of MEME, a motif discovery tool, to the integrated analysis tools which include CLUSTALW and TESS.

Animals↗

PubMed2026

Comprehensive in silico genomics analysis of global trends and host-specific emergence of aminoglycoside resistance in Staphylococcus aureus: a One-Health perspective.

BACKGROUND: Aminoglycosides remain clinically valuable against Staphylococcus aureus. Aminoglycoside resistance in S. aureus represents a critical One Health concern and is primarily driven by aminoglycoside-modifying enzymes (AMEs), which are frequently plasmid-encoded. Although regional studies have provided valuable insights, the global epidemiology of aminoglycoside resistance determinants remains poorly characterized because comprehensive data integrating human, animal, and environmental reservoirs are still lacking. This study addresses this gap by analyzing over 110,000 S. aureus genomes (2000-2025) to map the global resistome, quantify temporal and host-specific trends, and assess the association between genetic determinants and phenotypic resistance. METHODS: We performed a retrospective One Health meta-analysis of 110,309 S. aureus genomes collected between 2000 and 2025 from 128 countries. Genomes were quality-filtered and aminoglycoside resistance determinants were identified using NCBI AMRFinderPlus (v4.0.23). Multilocus sequence typing and host-source harmonization (Human, Animal, Environment, Unknown) enabled clonal and reservoir stratification. Temporal trends in gene prevalence and resistance burden were modeled with robust regression. Geographic and host-associated structuring of key genes was assessed via χ2 and enrichment tests. Machine-learning models (elastic-net, random forests, XGBoost) were benchmarked for minimum inhibitory concentration (MIC) prediction via nested cross-validation, with performance evaluated by mean absolute error, RMSE, and SHAP-based feature importance. All analyses were conducted in R and Python using publicly available, de-identified genomic data. RESULTS: Aminoglycoside resistance-associated genes were dominated by modifying enzyme determinants, with ant(6)-Ia, ant(9)-Ia, aph(3')-IIIa, sat4, aadD1, and aac(6')-Ie/aph(2'')-Ia occurring in 14-22% of isolates worldwide. Temporal analysis revealed significant declines in several major determinants, most notably ant(9)-Ia (-2.22 percentage points per year, p < 0.001), whereas apmA exhibited a non-significant decreasing trend in animal isolates. Host structuring was marked: human clinical isolates concentrated common determinants, while animal and environmental isolates harbored rare alleles (apmA, spw, str, spd). Geographic mapping confirmed near-universal distribution of common genes but focal restriction of rare ones. Publicly available phenotypic data indicated strong activity of amikacin, whereas gentamicin showed a distinct resistant subpopulation that closely corresponded with AME gene carriage. Genotype-phenotype analyses demonstrated strong concordance, with gene-rich complements predicting resistant MIC strata and absence of determinants predicting susceptibility. Analysis across different gene classes revealed frequent co-occurrence of aminoglycoside resistance genes with determinants from other classes, such as mecA, blaZ, and MLS_B, embedding them within multidrug-resistant (MDR) genomic contexts. CONCLUSION: Over 25 years, the prevalence of aminoglycoside resistance-associated genes in S. aureus has declined for several common determinants, while rare veterinary-linked alleles are emerging in animal isolates. Strong genotype-phenotype concordance supports genomic prediction for gentamicin and amikacin, where MIC data are available, although phenotypic confirmation remains essential. The frequent co-occurrence of aminoglycoside resistance genes with other antimicrobial resistance determinants indicates their integration within co-occurrence patterns of MDR genes, defined here as clusters of co-occurring resistance genes often carried on shared mobile genetic elements. These patterns highlight the need for integrated One Health surveillance combining clinical, veterinary, and environmental monitoring with plasmid-context resolution to anticipate emerging threats.

Aminoglycosides↗

PubMed1993

A mathematical model for dynamics of cardiovascular drug action: application to intravenous dihydropyridines in healthy volunteers.

A physiologically based mathematical model was built to describe the pharmacodynamic effects in response to the administration of intravenous (iv) dihydropyridine drugs in healthy volunteers. This model incorporates a limited number of hemodynamic variables, namely, mean arterial blood pressure (MAP), cardiac output (CO) or heart rate (HR), stroke volume (SV), and total peripheral resistance (TPR), into a closed-loop system supposed to represent essential features of the cardiovascular regulation. We also defined an additional auxiliary control variable (U) which is thought to represent primarily the role of the baroreceptor reflex. It was assumed that the variable U was related to MAP changes through both deviation- and rate-sensitive mechanisms. Other model parameters are the baseline levels for MAP, CO (or HR), and TPR, as well as time constants to account for further temporal aspects of the regulation. Finally, TPR was assumed to be linked to the plasma concentrations of dihydropyridine drugs via a conventional pharmacokinetic/pharmacodynamic (PK/PD) model, relying upon an effect compartment and a linear, hyperbolic, or sigmoidal relationship between the reduction in TPR and the drug concentrations at the effect site. The model characteristics were explored by studying the influence of various parameters, including baseline levels and deviation- and rate-sensitive control parameters, on the hemodynamic responses to a fictive constant rate i.v. infusion of a vasodilator drug. Attempts were also made to mimic literature data with nifedipine, following i.v. administration under both constant and exponentially decreasing infusion rates. The applicability of the model was demonstrated by fitting hemodynamic data following i.v. infusion of nicardipine to healthy volunteers, under experimental conditions similar to those described above for nifedipine. The effect model for the action of nicardipine on TPR, combined with the physiological model including a feedback control loop, allowed an adequate quantitative description of time profiles for both cardiac output and mean arterial pressure. The suggested model is a useful tool for integrated data analysis of hemodynamic responses to vasodilator drugs in healthy volunteers. Computer simulations suggest that a graded variation of a few model parameters--including baseline levels of TPR and MAP and the deviation-sensitive parameter of the arterial pressure control--would also be able to account for the pattern of hemodynamic response observed in hypertensive patients, which is qualitatively different to that seen in normotensive subjects. Extrapolation of drug response from the healthy volunteer to the hypertensive patient is allowed by our model. Its usefulness for an early evaluation of drug efficacy during drug development is under current investigation.

Adult↗

PubMed2005

PharmGKB: the pharmacogenetics and pharmacogenomics knowledge base.

The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) is an interactive tool for researchers investigating how genetic variation effects drug response. The PharmGKB web site, www.pharmgkb.org, displays genotype, molecular, and clinical primary data integrated with literature, pathway representations, protocol information, and links to additional external resources. Users can search and browse the knowledge base by genes, drugs, diseases, and pathways. Registration is free to the entire research community but subject to an agreement to respect the rights and privacy of the individuals whose information is contained within the database. Registered users can access and download primary data to aid in the design of future pharmacogenetics and pharmacogenomics studies.

Databases, Factual↗

PubMed1996

Quantitative clinical measure of spasticity in children with cerebral palsy.

OBJECTIVE: This investigation developed an objective measure to quantify the degree of spasticity. DESIGN: Specifications included a single variable that integrated key elements characterizing spasticity: velocity, range of motion, and resistance to passive motion. A dynamometer at a children's hospital quantified the passive resistance of the hamstrings to knee extension for a range of motion at 4 different speeds for the prospective descriptive investigation. PATIENTS: A convenience sample of six children with able bodies and 17 children with spastic diplegic cerebral palsy volunteered. DATA PROCESSING: Torque-angle data were processed to calculate the work done by the machine on the children for each speed and then determine the slope of the work-velocity curves. This slope was considered to be the measure of spasticity and it was hypothesized that children with cerebral palsy would have a greater slope than children with able bodies. An independent test determined whether a significant difference existed between groups (p < .05). RESULTS: Torque-angle data for children with able bodies indicated little change in passive resistance as a function of speed. Similar data for children with cerebral palsy indicated larger resistive torques with increasing speed. Slope from the work-velocity data was close to zero for children with able bodies [.003 J/(degrees/sec)], while the corresponding slope for children with cerebral palsy was approximately 10 times greater [.031 J/(degrees/sec)] and significantly different (p < .05). CONCLUSION: The slope of the work-velocity data integrates three major components characterizing spasticity, it is a single number that can easily be evaluated and interpreted in a clinical setting, and it utilizes a machine that is available at many centers.

Adolescent↗

PubMed2005

[Distribution effects of orthographic similarity and priming by masked repetition].

This research centres on the effect that the orthographic neighbourhood has in the visual recognition of words. Specifically, we studied to what extent orthographic neighbourhood distribution, that is, the number of letter positions allowing formation of at least one neighbour (Pugh, Rexer, Peter, & Katz, 1994), influences the masked repetition priming effect. In a previous study (Mathey, Robert, & Zagar, 2004), interaction between neighbourhood distribution and orthographic priming was obtained in the lexical decision task. The Interactive Activation Model (IA; McClelland & Rumelhart, 1981) simulated this interaction. With the orthographic priming effect modified for distribution of the neighbourhood of target words, it was necessary to study whether the repetition priming effect also varied as a function of this indicator. Studying this interaction presents a major theoretical issue in specifying the activating and inhibiting processes presented in the IA model. Simulations were produced to obtain precise model predictions regarding the neighbourhood distribution effect in a repetitive priming situation for our experimental material. Target words all had two neighbours that were most frequent. These neighbours were isolated, that is, distributed over two letter positions (e.g.: TAUX/faux-toux), or associated, i.e., concentrated on one single position (e.g., SEAU/beau-peau). Targets were preceded by an identical priming (repetitive priming; e.g.: seau-SEAU) or by controlled priming (e.g., &&&&-SEAU). The simulation results obtained using the IA model show the facilitating effects of neighbourhood distribution and repetitive priming, but no interaction between these factors. The experimental results obtained in a lexical decision task confirm these predictions. Thus, the empirical data replicate the neighbourhood distribution's facilitating effect (Mathey & Zagar, 2000) as well as the facilitating effect of masked repetition (Forster & Davis, 1984). Finally, the most interesting result is that the facilitating effect of repetition is comparable for target words with associated neighbours and target words with isolated neighbours. An explanation of the combined effects of the orthographic neighbourhood and orthographic masked repetition priming, integrating data from literature as well as from the current study, is proposed within the framework of the IA model.

Humans↗

PubMed2003

Is social integration associated with the risk of falling in older community-dwelling women?

BACKGROUND: Social integration may lead to social support and influence that may in turn protect older community-dwelling adults from falls. METHODS: We examined incident falls over 3 years across quartiles of social integration scores in 6692 Caucasian women enrolled in the Study of Osteoporotic Fractures (mean age = 77 +/- 5 years). Social integration was assessed using family networks, friendship networks, and interdependence scores. Higher scores correspond to greater integration. Data were analyzed using Poisson regression with generalized estimating equations. Multivariate analyses were used to adjust for other risk factors and potential confounders. RESULTS: Women reported 11863 falls, averaging 0.60 falls per person annually, 95% confidence interval (CI) (0.57, 0.63), or 600 falls per 1000 women. In age-adjusted analysis, the average incidence rate of falls correlated inversely with family networks, interdependence, and composite integration scores (p <.05). In multivariate analysis, increasing family networks were inversely associated with fall risk, p(trend) =.02. Compared to the lowest quartile, the relative risk of falls (95% CI) associated with family network scores in the second, third, and fourth quartiles were 0.90 (0.79-1.03), 0.86 (0.74-1.00), and 0.84 (0.71-0.99), respectively. CONCLUSIONS: Strong family networks may protect against the risk of falls in older community-dwelling adults.

Accidental Falls↗

PubMed1994

Financial risk, accountability and outcome management: using data to manage and measure clinical performance.

As health care reform and components of managed competition begin to infiltrate the health care system, health care providers will be facing significant challenges over the next several years in responding to priorities that mandate the delivery of appropriate, comprehensive, cost-efficient high quality care. Changes in financial risk, increasing accountability, performance documentation, and outcome measurements will hold providers more responsible for the input and output of services provided. In an effort to respond to these challenges, health care providers will have to rely on integrated data systems to identify opportunities for improvement in an effort to more effectively manage and measure the impact of health care delivery as patients move through the health care system.

Competitive Medical Plans↗

PubMed1988

A successful experiment to reduce unnecessary laboratory use in a community hospital.

A series of interventions at a 228-bed general hospital provided physicians with feedback at regular intervals concerning the amount of laboratory services employed in treating their patients. Case-mix-adjusted estimates of laboratory tests allowed each physician to compare use of laboratory tests with that of peers in the same department at the same hospital. Physicians with "excess" practice patterns ordered hundreds more laboratory tests than average each year. A multifaceted educational program included the following: 1) meetings were held concerning costs and unnecessary laboratory tests; 2) physicians were given descriptions of their practice patterns relative to their peers as part of both large and small departmental discussions; 3) the feedback was repeated a year later; 4) a consensus conference established guidelines for test ordering; and 5) a sample of patient records was examined for appropriateness of laboratory test ordering. A total of 37% of a sample of tests ordered during the baseline period by physicians with "excess" practice patterns was classified as inappropriate. The intervention resulted in a reduction of 1.8 tests per patient (P = 0.0005). Eight of the nine tests individually showed reductions in use. Charge data from the target hospital showed a statistically significant reduction in laboratory charges per patient in the quarter following program initiation (P = 0.02) and no evidence for change in a group of five comparison hospitals. There was no evidence for reductions in the ordering of essential tests. These results demonstrate a cost-effective approach to reducing unnecessary costs that can be implemented in hospitals with integrated data systems.

Clinical Laboratory Techniques↗

PubMed2002

Data standardisation in GlycoSuiteDB.

GlycoSuiteDB, a database of glycan structures, has been constructed with an emphasis on quality, consistency and data integrity. Importance has been placed on making the database a reliable and useful resource for all researchers. This database can help researchers to identify what glycan structures are known to be attached to certain glycoproteins, as well as more generally identifying what types of glycan structures are associated with different states, for example, different species, tissues and diseases. To achieve this, a major effort has gone into data standardisation. Many rules and standards have been adopted, especially for representing glycan structure and biological source information. This paper describes some of the challenges faced during the continuous development of GlycoSuiteDB.

Animals↗

PubMed1989

Differences between patient and family assessments of depression in Alzheimer's disease.

A structured interview covering the DSM-III criteria for major depression was adapted for separate use with Alzheimer's disease patients and with their families. Data from 36 patients yielded a depression rate of 13.9%, whereas information from their families indicated that the rate was 50.0%. This disagreement reflected greater family endorsement of patients' loss of interest or pleasure, irritability, fatigue, and feelings of worthlessness. Use of DSM-III-R criteria narrowed but did not eliminate the discrepancy between patients' and families' assessments of the patients' depression. Uniform procedures for gathering and integrating data from the family that are relevant to diagnosis in this group are indicated.

Aged↗

PubMed1995

Dimensional modeling: beyond data processing constraints.

The focus of information processing requirements is shifting from the on-line transaction processing (OLTP) issues to the on-line analytical processing (OLAP) issues. While the former serves to ensure the feasibility of the real-time on-line transaction processing (which has already exceeded a level of up to 1,000 transactions per second under normal conditions), the latter aims at enabling more sophisticated analytical manipulation of data. The OLTP requirements, or how to efficiently get data into the system, have been solved by applying the Relational theory in the form of Entity-Relation model. There is presently no theory related to OLAP that would resolve the analytical processing requirements as efficiently as Relational theory provided for the transaction processing. The "relational dogma" also provides the mathematical foundation for the Centralized Data Processing paradigm in which mission-critical information is incorporated as 'one and only one instance' of data, thus ensuring data integrity. In such surroundings, the information that supports business analysis and decision support activities is obtained by running predefined reports and queries that are provided by the IS department. In today's intensified competitive climate, businesses are finding that this traditional approach is not good enough. The only way to stay on top of things, and to survive and prosper, is to decentralize the IS services. The newly emerging Distributed Data Processing, with its increased emphasis on empowering the end user, does not seem to find enough merit in the relational database model to justify relying upon it. Relational theory proved too rigid and complex to accommodate the analytical processing needs. In order to satisfy the OLAP requirements, or how to efficiently get the data out of the system, different models, metaphors, and theories have been devised. All of them are pointing to the need for simplifying the highly non-intuitive mathematical constraints found in the relational databases normalized to their 3rd normal form. Object-oriented approach insists on the importance of the common sense component of the data processing activities. But, particularly interesting, is the approach that advocates the necessity of 'flattening' the structure of the business models as we know them today. This discipline is called Dimensional Modeling and it enables users to form multidimensional views of the relevant facts which are stored in a 'flat' (non-structured), easy-to-comprehend and easy-to-access database. When using dimensional modeling, we relax many of the axioms inherent in a relational model. We focus on the knowledge of the relevant facts which are reflecting the business operations and are the real basis for the decision support and business analysis. At the core of the dimensional modeling are fact tables that contain the non-discrete, additive data. To determine the level of aggregation of these facts, we use granularity tables that specify the resolution, or the level/detail, that the user is allowed to entertain. The third component is dimension tables that embody the knowledge of the constraints to be used to form the views.

Electronic Data Processing↗

PubMed2026

GICPIdb: an archival repository of multimodal data focusing on pathological images for gastrointestinal cancers.

INTRODUCTION: Deep learning (DL) shows great potential for predicting biomarkers from routine histopathological slides of gastrointestinal (GI) cancers. Yet most existing models are validated on limited patient cohorts, while pathological image annotation and molecular marker standardization demand substantial professional expertise. To address these gaps, we constructed the Gastrointestinal Cancer Pathological Image Archive (GICPIdb, gicpidb.shubuzuo.top), a dedicated database and web platform covering seven major GI cancer types. METHODS: High-quality hematoxylin and eosin (H&E)-stained whole-slide images were collected from multiple sources and uniformly processed. Image annotations were performed by board-certified pathologists following standardized protocols. GICPIdb offers five interactive web modules for data uploading, quality control, feature extraction, online annotation and AI-based prediction. Its intuitive interface supports data browsing, retrieval, visualization and downloading. RESULTS: The database houses 2,863 pathologist-annotated, uniformly processed, high-quality H&E stained images collected from 2,655 patients. Of these, 1,699 patients were sourced from The Cancer Genome Atlas (TCGA), 182 from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and 424 from China-Japan Friendship Hospital and 350 from Chifeng Municipal Hospital in Inner Mongolia, China. It also integrates data on over 50 key molecular markers (e.g., MSI, TMB) and prognostic labels related to survival, recurrence and metastasis. DISCUSSION: GICPIdb aims to promote the development of DL-driven AI tools for cancer research and clinical translation. The multi-institutional data collection and standardized annotation pipeline are expected to enhance the generalizability and reproducibility of AI-based prediction models across diverse patient populations.

deep learning↗

PubMed2006

Use of the land snail Helix aspersa as sentinel organism for monitoring ecotoxicologic effects of urban pollution: an integrated approach.

Atmospheric pollution from vehicular traffic is a matter of growing interest, often leading to temporary restrictions in urban areas. Although guidelines indicate limits for several parameters, the real toxicologic impacts remain largely unexplored in field conditions. In this study our aim was to validate an ecotoxicologic approach to evaluate both bioaccumulation and toxicologic effects caused by airborne pollutants. Specimens of the land snail Helix aspersa were caged in five sites in the urban area of Ancona, Italy. After 4 weeks, trace metals (cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc) and polycyclic aromatic hydrocarbons (PAHs) were measured and these data integrated with the analyses of molecular and biochemical responses. Such biomarkers reflected the induction of detoxification pathways or the onset of cellular toxicity caused by pollutants. Biomarkers that correlated with contaminant accumulation included levels of metallothioneins, activity of biotransformation enzymes (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase), and peroxisomal proliferation. More general responses were investigated as oxidative stress variations, including efficiency of antioxidant defenses (catalase, glutathione reductase, glutathione S-transferases, glutathione peroxidases, and total glutathione) and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals, onset of cellular damages (i.e., lysosomal destabilization), and loss of DNA integrity. Results revealed a marked accumulation of metals and PAHs in digestive tissues of organisms maintained in more traffic-congested sites. The contemporary appearance of several alterations confirmed the cellular reactivity of these chemicals with toxicologic effects of potential concern for human health. The overall results of this exploratory study suggest the utility of H. aspersa as a sentinel organism for biomonitoring the biologic impact of atmospheric pollution in urban areas. Key words: atmospheric pollutants, bioindicators, biomarkers, DNA integrity, lysosomes, metallothioneins, oxidative stress, peroxisomes, polycyclic aromatic hydrocarbons, trace metals.

Air Pollutants↗