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Molluscan shellfish biomarker study of the Quebec, Canada, Saguenay Fjord with the soft-shell clam, Mya arenaria.

A spatial and temporal survey of six sites in the Saguenay Fjord and of one adjacent site in the St. Lawrence River estuary (Quebec, Canada) was undertaken to study the possible effects of anthropogenic contaminant input on soft-shell clam (Mya arenaria) populations. Bivalve sampling sites were selected because they reflected a range of areas representative of either no known (or apparent) pollution sources or of areas potentially influenced by different gradients and types of contamination sources. The most upstream site selected in the Saguenay Fjord, nearest to a highly populated and industrialized sector, and the most downstream site, near its mouth with the St. Lawrence River estuary, spanned a distance of some 70 km and encompassed the entire intertidal area suitable for Mya arenaria habitat. To measure effects in collected animals, we used a comprehensive battery of biomarkers composed of metallothionein-like proteins (MT), 7-ethoxyresorufin O-deethylase activity (EROD), DNA damage (DD), lipid peroxidation (LPO), vitellinlike proteins (Vn), phagocytosis (PHAG), nonspecific esterase (NspE) activity, and condition factor (weight-to-length ratio of clams). Vn, PHAG, DD, and NspE biomarkers were assayed in hemolymph (or hemocytes), whereas others (MT, EROD, LPO) were determined in the digestive gland. Whole-tissue metal content was also quantified in clams collected in the spatial survey. The spatial survey conducted in June 1997 showed significant effects at all sites, and principal component analysis indicated in addition that the more important responses were linked to the MT, LPO, and NspE biomarkers. Clams collected from sites closest to the upstream reaches of the fjord generally displayed higher levels of tissue metals (cadmium, manganese), as well as greater responses of NspE activity, MT, LPO, and PHAG. Animals collected from sites influenced by municipal wastewaters had higher levels of Vn, suggesting the presence of environmental estrogens. The results of the temporal survey (six monthly samplings of clams at three sites from May through October, 1997) showed that the bivalve reproductive cycle (vitellogenesis and spawning) can modulate the expression of several biomarkers. Vn levels, for example, were positively correlated with DD and EROD and negatively correlated with MT, suggesting that reproduction can influence the susceptibility of clams to some contaminants. Discrimination analysis over the 6 months of sampling revealed that the mean value of the discriminant function changed significantly over time, suggesting important changes in the relative contribution of each biomarker. In short, this study has provided evidence that clam populations in the Saguenay Fjord are impacted by multiple sources of contamination whose effects can be modulated by reproduction.

Animals↗

Biomarker conservation in primary and metastatic epithelial ovarian cancer.

PURPOSE: The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS: Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied. RESULTS: A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluation of urinary biomarkers for radical-induced liver damage in rats treated with carbon tetrachloride.

Carbon tetrachloride (CCl4) is a model compound for inducing free radical damage in liver. In this study 10 biomarkers in rats treated i.p. with three different single doses of CCl4 (0.25, 0.50, and 1.00 ml/kg body wt) were measured dose and time dependently and compared to evaluate these urinary products as noninvasive biomarkers for radical damage. Eight degradation products of lipid peroxides, namely, formaldehyde, acetaldehyde, acetone, propanal, butanal, pentanal, hexanal, and malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and coproporphyrin III were measured in this study. As general measures of toxicity, several clinical chemical parameters (n = 12) and histopathological damage were determined. A dose-dependent increase in both the clinical parameters and the lipid degradation products was found. Increases in lipid degradation products were statistically significant at doses of 0.5 and 1 ml/kg CCl4. An increase in these products was already found in the first 12 h after exposure. At the lowest dose, 0.25 ml/kg CCl4, acetaldehyde and propanal already showed a statistically significant increase as well. No change in the urinary levels of 8-OH-dG could be found in this study and a decrease in the urinary excretion of coproporphyrin III was found. It is concluded that 8-OH-dG and coproporphyrin III are not useful biomarkers for radical damage induced by CCl4. Lipid degradation products, however, are promising noninvasive biomarkers for in vivo radical damage, although the precise specificity of these biomarkers for damage induced by radicals needs to be further investigated.

8-Hydroxy-2'-Deoxyguanosine↗

Plasma and cerebrospinal fluid-based protein biomarkers for motor neuron disease.

Motor neuron diseases (MNDs) and, in particular, amyotrophic lateral sclerosis (ALS), are a heterogeneous group of neurologic disorders characterized by the progressive loss of motor function. In ALS, a selective and relentless degeneration of both upper and lower motor neurons occurs, culminating in mortality typically within 5 years of symptom onset. However, survival rates vary among individual patients and can be from a few months to >10 years from diagnosis. Inadequacies in disease detection and treatment, along with a lack of diagnostic and prognostic tools, have prompted many to turn to proteomics-based biomarker discovery efforts. Proteomics refers to the study of the proteins expressed by a genome at a particular time, and the proteome can respond to and reflect the status of an organism, including health and disease states. Although an emerging field, proteomic applications promise to uncover biomarkers critical for differentiating patients with ALS and other MNDs from healthy individuals and from patients affected by other diseases. Ideally, these studies will also provide mechanistic information to facilitate identification of new drug targets for subsequent therapeutic development. In addition to proper experimental design, standard operating procedures for sample acquisition, preprocessing, and storage must be developed. Biological samples typically analyzed in proteomic studies of neurologic diseases include both plasma and cerebrospinal fluid (CSF). Recent studies have identified individual proteins and/or protein panels from blood plasma and CSF that represent putative biomarkers for ALS, although many of these proteins are not unique to this disease. Continued investigations are required to validate these initial findings and to further pursue the role of these proteins as diagnostic biomarkers or surrogate markers of disease progression. Protein biomarkers specific to ALS will additionally function to evaluate drug efficacy in clinical trials and to identify novel targets for drug design. It is hoped that proteomic technologies will soon integrate the basic biology of ALS with mechanistic disease information to achieve success in the clinical setting.

Amyotrophic Lateral Sclerosis↗

Biomarkers for the development of cancer vaccines: current status.

Significant improvements in our knowledge of tumor immunology have resulted in more sophisticated vaccine approaches for the treatment of cancer. However, research into biomarkers that correlate with the clinical outcome of immunotherapy has lagged behind vaccine development. To this extent, very few immunological or other markers exist that can be used in clinical trials for immunotherapy. In this review, we discuss the current status of biomarker development specifically for the monitoring and development of cancer vaccines. This includes immunological biomarkers (measurement of T-cell and cytokine responses), autoimmunity as a correlate for treatment outcome, and the possible development of multiple biomarkers using high-throughput proteomics technologies. The generation of such biomarkers will allow us to make clinical decisions about patient treatment at an earlier stage and should aid in shortening the development time for vaccines.

Animals↗

Assessment of teeth as biomarkers for skeletal fluoride exposure.

Skeletal fluorosis and dental fluorosis are diseases related to fluoride (F) ingestion. Bone is the largest storage site of F in our body. Therefore, bone F concentrations are considered biomarkers for total F body burden (exposure). However, difficult accessibility limits its use as a biomarker. Thus, a more accessible tissue should be considered and analyzed as a biomarker for total F body burden. The objective of this study, which was divided into two parts, was to evaluate teeth as a biomarker for skeletal F exposure. In part 1 of the study, 70 mice of three different strains (SWR/J, A/J and 129P3/J) were exposed to different levels of water fluoridation (0, 25, 50 and 100 ppm). Bone (femora and vertebrae) and teeth from these mice were then analyzed for F concentration using Instrumental Neutron Activation Analysis (INAA). In part 2 of the study, human teeth (enamel and dentin) and bone from 30 study subjects were collected and analyzed for F concentration using INAA. Study subjects lived in areas with optimum levels of water fluoridation (0.7 and 1 ppm) and underwent therapeutic extraction of their unerupted third molars. The values of bone and teeth F concentration were correlated for parts 1 and 2 of this study. The results showed that in the animal model, where animals were exposed to a wide range of F in their drinking water, tooth [F] correlated with bone [F]. However, no correlation was seen between bone and enamel F concentrations or between bone and dentin F concentrations in the human samples. Therefore, teeth are not good biomarkers for skeletal F exposure in humans when exposure is confined to optimum levels of F in the drinking water.

Adolescent↗

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

Biomarkers↗

Biomarkers of exposure and reproduction-related effects in mussels exposed to endocrine disruptors.

Biomarkers are useful tools to study the health of estuarine and marine ecosystems. Biomarkers can be measured in different organisms, but mussels have acquired a global importance as sentinels in marine pollution-monitoring programs. In the present work, we aimed to determine the effects of different endocrine disruptors in mussels by using peroxisome proliferation as a biomarker of exposure to organic pollutants and the levels of vitellogenin (Vtg)-like proteins as biomarker of endocrine disruption. In experiment 1, mussels Mytilus edulis were exposed for 3 weeks to North Sea crude oil (NSO 0.5 ppm) and a mixture of 0.5 ppm NSO, 0.1 ppm alkylphenol mix, and 0.1 ppm extra polycyclic aromatic hydrocarbons (PAHs) (MIX). In experiment 2, mussels were exposed for 3 weeks to diallylphthalate (DAP 50 ppb), bisphenol-A (BPA 50 ppb), and tetrabromodiphenylether (TBDE 5 ppb). Peroxisome proliferation was assessed by measuring acyl-CoA oxidase (AOX) activity and peroxisomal volume density (VVp) in digestive gland. Vtg-like protein levels were measured in gonads by the alkali-labile phosphate (ALP) method. Gonad was also analyzed histologically, and the gonad index (GI) calculated. Mussels exposed to NSO and MIX showed significantly increased AOX activities and VVP compared with control animals. Significantly higher VVP was also found in DAP- and TBDE-exposed mussels. Effects on ALP and GI depended significantly on sex and time of year. In female mussels, ALP levels and GI were lower in the NSO group. In male mussels, ALP levels were significantly increased in the MIX group. The volume density of athretic oocytes was higher in the NSO and MIX exposure groups than in controls, and gonad resorption was observed in the BPA exposure group. Our results confirm the usefulness of peroxisome proliferation as a biomarker of exposure to organic contaminants in mussels and indicate that changes in Vtg-like proteins could be used as potential indicator of pollutant effects on mussel reproduction.

Acyl-CoA Oxidase↗

Serum biomarkers for detection of breast cancers: A prospective study.

Using surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF), Li et al. [Clin Chem 48(8): 1296-1304, 2002] identified 3 serum biomarkers, BC1 (4.3 kDa), BC2 (8.1 kDa) and BC3 (8.9 kDa), whose combination significantly detects breast cancer patients from non-cancer controls. This work aimed to validate these biomarkers in an independent prospective study. We screened 89 serum samples including 49 breast cancers at pT1-4N0M0 (n = 23), pT1-4N1-3M0 (n = 17) or pT1-4N0-3M1 (n = 9) stages, 13 benign breast diseases and 27 healthy women. The BC2 biomarker significance was not recovered. However, we found 2 peaks that we named BC1a (4286 Da) and BC1b (4302 Da), that could correspond to Li's BC1 since they significantly decrease in breast cancers (p < 0.00007 and p < 0.0002, respectively). Similarly, BC3a (8919 Da) and BC3b (8961 Da) are significantly increased in breast cancers (p < 0.02 and p < 0.0002, respectively) and could correspond to the Li's BC3. For each biomarker we defined stringent (no errors) and flexible (less than 10% errors) cut-off values and tested the power of the combined BC1a/BC1b/BC3a/BC3b stringent and flexible profiles to discriminate breast cancers. They identified 33% and 45% cancers, respectively. Applied to the same series, Ca 15.3 test identified 22% patients. Interestingly, in association with the BC1a/BC1b/BC3a/BC3b profiles, Ca 15.3 improved the number of detected cancers indicating that it is an independent parameter. Collectively, our data partially validate those of Li's study and confirm that the BC1 and BC3 biomarkers are helpful for breast cancer diagnosis.

Adenocarcinoma, Mucinous↗

Use of biomarkers in epidemiologic studies: minimizing the influence of measurement error in the study design and analysis.

The inclusion of biomarkers measured on the continuous scale, such as endogenous sex hormones or antioxidant levels, has become common in epidemiologic studies, and introduces additional sources of error that are specific to biomarkers. This includes error associated with specimen collection, processing, and storage; laboratory error (both within and between batch); and variability in the biomarker levels over time within an individual. In this review, we discuss and recommend study design and analytic strategies to deal with these sources of measurement error. In particular we describe methods to prevent or minimize some sources of error through appropriate sample collection and storage, communication with the laboratory, proper batching of samples, and participant matching. We also discuss how to quantify error related to biomarkers, focusing on issues of quality control, pilot studies, and how to measure within-person stability over time. Further, we discuss analytic issues for dealing with laboratory and within-person variability. Finally we recommend that journals standardize the reporting of biomarker assays in scientific manuscripts.

Biomarkers↗

The 'Coral Bulker' fuel oil spill on the north coast of Portugal: spatial and temporal biomarker responses in Mytilus galloprovincialis.

In December 2000, the ship 'Coral Bulker' ran aground at the entrance of the port of Viana do Castelo (North-west coast of Portugal). A large amount of fuel oil was spilled and part of it reached the shore. To evaluate the spatial and temporal impact of this oil spill, a field study, and several laboratory toxicity tests were performed using Mytilus galloprovincialis as biological indicator of environmental contamination and the biomarkers glutathione S-transferases (GSTs) and acetylcholinesterase (AChE) as indicative criteria. Fifteen days after the oil spill, mussels collected at stations located near the ship presented higher and lower values of GSTs and AChE activity, respectively. These results, and those obtained in the laboratory toxicity tests, evidence that these biomarkers were sensitive indicators of exposure to this kind of pollution and were able to monitor a spatial impact of the oil spill of at least 10 km, confirming the higher level of contamination near the ship and a contamination gradient along the sampling stations. One year after the accident, such a contamination gradient was no longer evident. This study highlight the potential suitability of a biomarker approach for assessing spatial and temporal impacts of marine pollution accidents, such as fuel oil spills, suggesting the inclusion of these biomarkers in risk assessment studies, as cost-effective and early warning recognized tools. Major advantages and limitations of the biomarker approach used in this study are further discussed.

Acetylcholinesterase↗

Evaluating measures of hematology and blood chemistry in male rhesus monkeys as biomarkers of aging.

Reliable and valid biomarkers of aging can provide valuable tools for examining the effectiveness of interventions that may influence the rate of aging processes. However, a standardized method for identifying biomarkers of aging has yet to be developed. The current analysis focused on hematology and blood chemistry variables obtained from a 5-year longitudinal study of male rhesus monkeys (N = 29) on a diet restriction regime known to retard aging processes and extend lifespan in laboratory rodents (70% of the diet intake of controls). For the current analysis, the major screening criteria for identifying candidate biomarkers of aging were cross-sectional and longitudinal correlation with chronological age (CA) and stability of individual differences. Six potential variables from the battery of blood chemistry tests were identified: 1) serum glutamic oxalacetic transaminase; 2) alkaline phosphatase; 3) total protein; 4) globulin; 5) blood urea nitrogen to creatinine ratio; and 6) phosphates. When submitted to principle component analysis, these variables loaded onto a single component that accounted for over 50% of the total variance to indicate marked covariance among them. By applying the factor score coefficients from the first principle component, an equation was derived for estimating a biological age score (BAS) for each individual monkey. A comparison of BAS between control and diet-restricted monkeys revealed no statistically significant difference at present; however, the slope of the regression of BAS onto CA appeared steeper for the control group compared to the experimental group. Thus, while demonstration of the validity of the candidate biomarkers awaits further evidence, a strategy by which additional biomarkers of aging can be identified is proposed as an improvement over past approaches.

Aging↗

Evaluation and management of the acutely dyspneic patient: the role of biomarkers.

The etiology of dyspnea can often be difficult to rapidly and accurately determine and can delay timely and appropriate therapies. The current literature reveals important diagnostic, prognostic, and therapeutic implications of several currently used biomarkers: sensitive d -dimer, myoglobin, creatine kinase-MB, cardiac troponins, and b-type natriuretic peptide. These biomarkers were found to have a high sensitivity and negative predictive value for rapidly ruling out potential serious etiologies of dyspnea, namely, pulmonary embolism (PE), acute myocardial infarction (AMI), and congestive heart failure (CHF). In the setting of a low to moderate pretest probability of PE, a negative sensitive d -dimer can rule out a PE with 97% accuracy. After 10 hours from the onset of symptoms, normal levels of myoglobin, creatine kinase-MB, and cardiac troponin I can rule out an AMI with greater than 96% accuracy. A b-type natriuretic peptide level less than 80 pg/mL can confidently rule out decompensated CHF with greater than 99% accuracy. However, no literature was found analyzing the use of these biomarkers in combination. A dyspnea biomarker panel could rapidly and accurately assist a clinician to rule out PE, AMI, and CHF. If a PE, AMI, or CHF is determined to be the cause of dyspnea, a biomarker panel could help risk stratify and help determine initial therapies. Subsequent clinical research is needed to corroborate this postulation.

Antifibrinolytic Agents↗

Cellular biomarkers of exposure and biological effect in hepatocytes of turbot (Scophthalmus maximus) exposed to Cd, Cu and Zn and after depuration.

Cellular biomarkers of exposure and biological effects were measured in hepatocytes of turbot exposed to either Cd, Cu or Zn at concentrations of 1 and 10 mg/l seawater for 7 days and after depuration for 14 days. Metal content in hepatocyte lysosomes was determined by image analysis after autometallography (AMG) as volume density of autometallographed black silver deposits (Vv(BSD)). Metallothionein (MT) levels were quantified on liver sections by microdensitometry after immunohistochemical staining with a polyclonal anti cod-MT antibody (MT-OD), and in the cytosolic fraction of hepatocytes by difference pulse polarography (MT-DPP). Lysosomal structural changes (lysosomal volume, surface and numerical densities--Vv(LYS), Sv(LYS) and Nv(LYS-), and surface-to-volume ratio S/V(Lys)) were quantified by image analysis after demonstration of beta-glucuronidase activity on liver cryotome sections. Vacuolisation produced by metal-exposure in hepatocytes was quantified by stereology as volume density of vacuoles (Vv(VAC)). Exposure time and metal concentrations significantly affected Vv(BSD) in lysosomes, MT levels and the degree of vacuolisation after 1 h and 1 day exposure to the three metals. The highest Vv(BSD), MT and Vv(VAC) values were recorded after 7 days exposure in all cases. MT-OD and MT-DPP were significantly correlated with Vv(BSD). Vv(LYS) in hepatocytes increased significantly after exposure to the metals. Exposure biomarkers returned to control values after depuration with the exception of those turbots that had been exposed to 10 mg Cd/l. Alike, Vv(LYS) and Sv(lys) (Cu exposure) and Nv(LYS) (Cd and Zn exposures) returned to control values after depuration. It has been therefore demonstrated that the biomarkers used are reversible and return towards control levels once metal exposure ceases. Overall, it is concluded that Vv(BSD), MT-levels and lysosomal responses are valuable biomarkers to assess metal exposure and its effects in turbot, although in quantitative terms the biomarker response varied between metals.

Analysis of Variance↗

Novel biomarkers in preeclampsia.

Preeclampsia is a pregnancy-associated disease with maternal symptoms, but placental origin. Although clinical symptoms are late, systemic and maternal, the origin of preeclampsia is early, local and placental. Despite that various protein biomarkers display changed levels in maternal serum at presymptomatic stages, they lack discriminative and predictive power in individual patients. In contrast to protein markers, placental RNA analyzed in maternal plasma permits rapid screening of novel biomarkers including markers not accessible by antibody based assays. This includes transcription factors, non-coding RNA, epigenetic features, as well as genes functionally or genetically linked with preeclampsia. By reviewing genes with placental expression in the Human SymAtlas and comparison with proven qualifiers, a large set of RNA biomarkers was targeted for use in maternal plasma. These biomarkers qualify as novel RNA biomarkers for the presymptomatic detection in first trimester of pregnancy-associated diseases with placental origin and/or dysfunction such as pregnancy-induced hypertension without or with proteinuria (preeclampsia), the HELLP syndrome, and intrauterine growth restriction.

Biomarkers↗

Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. METHODS: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. RESULTS: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. CONCLUSIONS: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Adolescent↗

Interannual variability in fish biomarkers in a contaminated temperate urban estuary.

During the past decade the Swan-Canning estuary, Western Australia, has shown signs of stress which has been attributed to high nutrient inputs. There is little information on the effect of nonnutrient contaminants on biota inhabiting the estuary. A suite of biomarkers was measured on black bream (Acanthopagrus butcheri) to determine whether annual variations in fish biomarkers exist in the wet (winter) and dry (summer) seasons. Serum sorbitol dehydrogenase showed no significant differences between years, indicating that measured mixed-function oxygenase (MFO) enzyme activities were not affected by annual variations in hepatic tissue damage. Ethoxyresorufin-O-deethylase activity was lower in female black bream than in male fish while ethoxycoumarin-O-deethylase activity was not influenced by gender. Biomarker levels measured at various sites confirm that major roads and drains are significant contributors of MFO-inducing chemicals into the Swan-Canning estuary. No consistent upstream or downstream gradient in biomarker response was identified. The ratio of naphthalene-type to benzo(a)pyrene-type biliary metabolites was linked to runoff from urban areas into the estuary. There was high annual variability in all biomarkers in both seasons, suggesting that biannual monitoring is required to evaluate the effect of contaminants on the biota in the estuary.

7-Alkoxycoumarin O-Dealkylase↗

Current issues relating to drug safety especially with regard to the use of biomarkers: a meeting report and progress update.

An expert group met in Leiden to review the state-of-the-art in detecting drug-related safety problems and to review the role of biomarkers and modelling techniques. It was clear that new drugs are not necessarily safer than old drugs, despite much larger clinical trial programs. Larger or longer clinical trials may be unfeasible and postmarketing surveillance is not being undertaken systematically enough to ensure safety. Biomarkers could improve drug safety by detecting drug-related signals early but determining whether the biomarker is on the causal pathway to toxicity is difficult. The maturity and utility of safety-related biomarkers varies among target organ systems. A consortium approach to assimilate a large amount of biomarker-related safety signals incorporating this information into mechanism-based models may provide a useful way forward. However no techniques will ensure that drugs are perfectly safe and communication with the public is required to achieve mutual understanding of benefit risk/balance assessments.

Biomarkers↗