Major correlates of mercury in small fish and common loons (Gavia immer) across four large study areas in Canada.

We investigated mercury (Hg) concentrations in small fish (mainly yellow perch, Perca flavescens; ∼60% of fish collected) and in blood of common loons (Gavia immer) that prey upon them during the breeding season on lakes in 4 large, widely separated study areas in Canada (>13 lakes per study area; total number of lakes = 93). Although surface sediments from lakes near a base metal smelter in Flin Flon, Manitoba had the highest Hg concentrations, perch and other small fish and blood of common loon chicks sampled from these same lakes had low Hg concentrations similar to those from uncontaminated reference lakes. Multiple regression modeling with AIC analysis indicated that lake pH was by far the most important single factor influencing perch Hg concentrations in lakes across the four study areas (R(2) = 0.29). The best model was a three-variable model (pH + alkalinity + sediment Se; Wi = 0.61, R(2) = 0.85). A single-variable model (fish Hg) best explained among-lake variability in loon chick blood Hg (Wi = 0.17; R(2) = 0.53). From a toxicological risk perspective, all lakes posing a potential Hg health risk for perch and possibly other small pelagic fish species (where mean fish muscle Hg concentrations exceeded 2.4 µg/g dry wt.), and for breeding common loons (where mean fish muscle Hg concentrations exceeded 0.8 µg/g dry wt., and loon chick blood Hg exceeded 1.4 µg/g dry wt.) had pH < 6.7 and were located in eastern Canada.

Independent protein-profiling studies show a decrease in apolipoprotein A1 levels in schizophrenia CSF, brain and peripheral tissues.

Although some insights into the etiology of schizophrenia have been gained, an understanding of the illness at the molecular level remains elusive. Recent advances in proteomic profiling offer great promise for the discovery of markers underlying pathophysiology of diseases. In the present study, we employed two high-throughput proteomic techniques together with traditional methods to investigate cerebrospinal fluid (CSF), brain and peripheral tissues (liver, red blood cells and serum) of schizophrenia patients in an attempt to identify peripheral/surrogate disease markers. The cohorts used to investigate each tissue were largely independent, although some CSF and serum samples were collected from the same patient. To address the major confounding factor of antipsychotic drug treatment, we also included a large cohort of first-onset drug-naive patients. Apolipoprotein A1 (apoA1) showed a significant decrease in expression in schizophrenia patients compared to controls in all five tissues examined. Specifically, using SELDI-TOF mass spectrometry, apoA1 was found decreased in CSF from schizophrenia patients (-35%, P=0.00001) and, using 2D-DIGE, apoA1 was also found downregulated in liver (-30%, P=0.02) and RBCs (-60%, P=0.003). Furthermore, we found a significant reduction of apoA1 in sera of first-onset drug-naive schizophrenia patients using enzyme-linked immunosorbent assay (-18%, P=0.00008) and in two investigations of post-mortem brain tissue using western blot analysis (-35%, P=0.05; -51%, P=0.05). These results show that apoA1 is consistently downregulated in the central nervous system as well as peripheral tissues of schizophrenia patients and may be linked to the underlying disease mechanism.

Relationships among mercury, selenium, and neurochemical parameters in common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus).

Fish-eating birds can be exposed to levels of dietary methylmercury (MeHg) known or suspected to adversely affect normal behavior and reproduction, but little is known regarding Hg's subtle effects on the avian brain. In the current study, we explored relationships among Hg, Se, and neurochemical receptors and enzymes in two fish-eating birds--common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus). In liver, both species demonstrated a wide range of total Hg (THg) concentrations, substantial demethylation of MeHg, and a co-accumulation of Hg and Se. In liver, there were molar excesses of Se over Hg up to about 50-60 microg/g THg, above which there was an approximate 1:1 molar ratio of Hg:Se in both species. However, in brain, bald eagles displayed a greater apparent ability to demethylate MeHg than common loons. There were molar excesses of Se over Hg in brains of bald eagles across the full range of THg concentrations, whereas common loons often had extreme molar excesses of Hg in their brains, with a higher proportion of THg remaining as MeHg compared with eagles. There were significant positive correlations between brain THg and muscarinic cholinergic receptor concentrations in both species studied; whereas significant negative correlations were observed between N-methyl-D-aspartic acid (NMDA) receptor levels and brain Hg concentration. There were no significant correlations between brain Se and neurochemical receptors or enzymes (cholinesterase and monoamine oxidase) in either species. Our findings suggest that there are significant differences between common loons and bald eagles with respect to cerebral metabolism and toxicodynamics of MeHg and Se. These interspecies differences may influence relative susceptibility to MeHg toxicity; however, neurochemical responses to Hg in both species were similar.

Gene expression profiling in the adult Down syndrome brain.

The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear. We used whole genome microarrays to characterize for the first time the transcriptome of human adult brain tissue (dorsolateral prefrontal cortex) from seven DS subjects and eight controls. These data were coanalyzed with a publicly available dataset from fetal DS tissue and functional profiling was performed to identify the biological processes central to DS and those that may be related to late onset pathologies, particularly Alzheimer disease neuropathology. A total of 685 probe sets were differentially expressed between adult DS and control brains at a stringent significance threshold (adjusted p value (q) < 0.005), 70% of these being up-regulated in DS. Over 25% of genes on chromosome 21 were differentially expressed in comparison to a median of 4.4% for all chromosomes. The unique profile of up-regulation on chromosome 21, consistent with primary dosage effects, was accompanied by widespread transcriptional disruption. The critical Alzheimer disease gene, APP, located on chromosome 21, was not found to be up-regulated in adult brain by microarray or QPCR analysis. However, numerous other genes functionally linked to APP processing were dysregulated. Functional profiling of genes dysregulated in both fetal and adult datasets identified categories including development (notably Notch signaling and Dlx family genes), lipid transport, and cellular proliferation. In the adult brain these processes were concomitant with cytoskeletal regulation and vesicle trafficking categories, and increased immune response and oxidative stress response, which are likely linked to the development of Alzheimer pathology in individuals with DS.

Year-to-year correlations in blood metal levels among individuals of two species of North American sea ducks.

Sea duck populations have declined in North America. Contaminants, especially metals, have been listed as possible contributing factors. Sea ducks are long-lived. Thus, individuals chronically exposed to elevated metal levels may be at greatest risk. Information about long-term exposure (> or =1year) of individuals to metals is absent. To address this information gap, we examined year-to-year correlations among individual White-Winged Scoters and King Eiders in levels of blood cadmium, lead, mercury and selenium. Positive correlations (r> or =0.43), were found in six, five, five and two of seven correlations for cadmium, selenium, lead and mercury. Thus, certain individuals of these species may be exposed over two or more years to higher levels of cadmium, selenium and lead (but apparently not mercury) than other individuals. Single blood samples are appropriate metrics of exposure for studies that examine long-term effects of certain metals on these birds.

Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.

Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology to determine the expression of approximately 22,000 mRNA transcripts in post-mortem tissue from two brain regions in patients with bipolar disorder and matched healthy controls. Dorsolateral prefrontal cortex tissue from a cohort of 70 subjects and orbitofrontal cortex tissue from a separate cohort of 30 subjects was investigated. The final analysis included 30 bipolar and 31 control subjects for the dorsolateral prefrontal cortex and 10 bipolar and 11 control subjects for the orbitofrontal cortex. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing. In the orbitofrontal cortex, 393 differentially expressed transcripts were identified by microarray analysis and a representative subset was validated by quantitative real-time PCR. Pathway analysis revealed significant upregulation of genes involved in G-protein coupled receptor signalling and response to stimulus (in particular the immune response), while genes relating to the ubiquitin cycle and intracellular transport showed coordinated downregulation in bipolar disorder. Additionally, several genes involved in synaptic function were significantly downregulated in bipolar disorder. No significant changes in gene expression were observed in the dorsolateral prefrontal cortex using microarray analysis or quantitative real-time PCR. Our findings implicate the orbitofrontal cortex as a region prominently involved in bipolar disorder and indicate that diverse processes are affected. Overall, our results suggest that dysregulation of the ubiquitin pathway and synaptic function may be central to the disease process.

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress.

The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

Immune function, stress response, and body condition in arctic-breeding common eiders in relation to cadmium, mercury, and selenium concentrations.

We examined relationships between trace metal concentrations in tissues of common eider ducks (cadmium, mercury, and selenium) and selected biomarkers of health (stress response, immune function, and body condition). This study was conducted at an eider nesting colony in the Canadian arctic in 1998 and 1999. Capture-induced stress, measured as the rise in corticosterone concentrations following capture, was positively related (P=0.03) to renal cadmium concentration in 1998 when incubating eiders were sampled, but not in 1999 when prenesting eiders were sampled. Stress response was inversely related (P=0.02) to selenium concentrations in 1999. Following capture and blood sampling in 1999, eiders were placed in a flight pen on-site for eight days in order to examine immune function. Cell-mediated immunity, measured as the skin-swelling response to an intradermal injection of phytohemagglutinin-P, (PHA-P), was positively related (P=0.003) to hepatic selenium. The heterophil:lymphocyte ratio was inversely related (P=0.08) to hepatic selenium. In 1998, selenium was positively related to body mass (P=0.01), abdominal fat mass (P=0.07), kidney mass (P=0.03), and liver mass (P=0.07). In 1999, hepatic mercury was negatively related to abdominal fat mass (P=0.01), spleen mass (P=0.07) and body mass at capture (P=0.09) in prenesting eiders.

Concentrations of cadmium, mercury and selenium in blood, liver and kidney of common eider ducks from the Canadian arctic.

We determined concentrations of selected trace elements in livers, kidneys and blood samples from common eiders (Somateria mollissima borealis) from the eastern Canadian arctic during 1997 and 1998. Concentrations of total mercury and organic mercury were generally low in the livers of these birds (less than 6 and 4 microg g(-1) dry wt, respectively). Selenium ranged between 11-47 microg g(-1) in livers. Renal cadmium concentrations were among the highest ever published for this species (range: 47-281 microg g(-1)). The regressions of log-transformed concentrations of these trace elements in blood samples on those in liver or kidney were significant (all P-values < 0.05) and positive. However, except for organic mercury (R2 = 0.83), the co-efficients of determination were low to moderate (range of R2: 0.26-0.52), suggesting poor to moderate predictive capability. Furthermore, the relationships between total mercury in blood and liver changed between 1997 and 1998, suggesting that it would not be possible to predict consistently, concentrations of mercury in blood from those in liver based on samples taken in one year. Blood samples can be used to determine concentrations of these trace elements in common eiders (and probably other sea duck species as well). The use of blood samples is especially warranted when it is undesirable to kill the animal such as when working with rare or endangered sea duck species or when the objective is to relate trace element exposure to annual survival rates. However, the predictive equations developed here should not be used to predict expected concentrations in one type of tissue from those in the other.

Trace elements in king eiders and common eiders in the Canadian arctic.

We determined concentrations of selected trace elements in tissues of king and common eiders at three locations in the Canadian arctic. Renal and hepatic cadmium concentrations in king eiders at a location in the eastern arctic were among the highest ever recorded in eider ducks: there, they were higher in king eiders than in common eiders. Cadmium concentrations were lower in king eiders from the western arctic than in those from the east. In the western arctic, cadmium concentrations did not differ between species. Hepatic mercury and zinc were higher in king eiders than in common eiders. Zinc and selenium were higher in eiders from the western arctic than in those from the eastern arctic. Trace element concentrations in these two duck species were below published toxicity thresholds. Positive correlations in trace element concentrations in both species were found between total and organic hepatic mercury, renal and hepatic cadmium as well as hepatic zinc, copper, mercury, and cadmium. Body mass of common but not king eiders and spleen mass of both species were negatively correlated with mercury concentrations. In common eiders, the number of nematode parasites was positively correlated with total and organic mercury. Histopathological evidence of kidney or liver lesions that are typical of trace metal poisoning was not found. We did not find evidence to support the hypothesis that trace metal exposure may be contributing to adverse effects on the health of individuals of these species.

Hemograms for and nutritional condition of migrant bald eagles tested for exposure to lead.

Plasma proteins, hematocrit, differential blood counts were examined and nutritional condition was estimated for bald eagles (Haliaeetus leucocephalus) trapped (n = 66) during antumn migration, 1994-95 at Galloway Bay (Saskatchewan, Canada), for the purposes of estimating prevalence of exposure to lead. Sex and age differences in hematocrit and plasma proteins were not observed; however, female eagles exhibited larger median absolute heterophil counts than males. Hematologic values were similar to those previously reported from eagles in captivity. Departures from expected hematological values from a healthy population of eagles were not observed in birds with elevated levels of blood lead (> or =0.200 microg/ml). Similarly, nutritional condition was not related to blood-lead concentrations. Therefore, it appears that lead exposure in this population was below a threshold required to indicate toxicological alteration in the hematological values and index of nutritional condition that we measured.

Exposure of migrant bald eagles to lead in prairie Canada.

The prevalence of elevated exposure to lead was assessed in a migrant population of bald eagles (Haliaeetus leucocephalus) at a waterfowl staging area in the southern portion of the Canadian prairies, from September to November, 1992-1995. Of 103 eagles, 8% exhibited blood lead (PbB) concentrations suggestive of elevated exposure to lead (> or = 0.200 microgram ml-1 wet wt.). PbB concentrations in eagles from the study area ranged from < 0.01 to 0.585 microgram ml-1, while those of nestling eagles from a reference site indicated normal or background exposure (< 0.01 microgram ml-1). No differences in the prevalence of elevated exposure were detected among genders or age classes (0.5- and > or = 1.5-year-old birds) (P > 0.05). The prevalence of elevated exposure was significantly greater in November than in October (21.7 vs. 3.8%) (all years: chi 2Y = 5.75, P = 0.017). Eagles with shotshell pellets in the digestive tract did not have accompanying high PbB concentrations. The prevalence of elevated lead exposure in this study was low in comparison to other areas in North America. Potential biases in the trapping technique as they relate to interpreting the results are addressed.

Health care professionals and industry: reducing conflicts of interest and established best practices.

The relationship between health care providers and pharmaceutical companies and other commercial interests is ethically complex. The common practice of gift giving takes many forms including free samples, sponsorship of medical education, loan of equipment, and gifts ranging from those of nominal value such as pens to more valuable gifts such as golf outings or dinners. Gift giving is a practice that serves both the recipient and the giver, but, in the medical setting, it raises the question of whether this is to the detriment of patient care. Although health care professionals may believe they are able to ignore influence from commercial interests, human judgment research indicates that decision-makers are generally unaware of biases affecting their decisions. This is an issue of organizational ethics as well. Institutions that allow commercial interests to give some form of gift are allowing the appearance of bias as well as placing the burden of avoiding bias on the individual rather than on the institution. Conflict-of-interest analysis indicates that best practice is to limit or eliminate the influence of commercial interests, ensuring that professionals are better able to exercise their independent objective judgment.

Concentrations of lead in liver, kidney, and bone of bald and golden eagles.

The diagnosis of lead poisoning in eagles relies on autopsy information and residue analysis of lead in certain tissues, usually liver or blood. Similarly, the assessment of elevated lead exposure in eagles depends on the determination of lead concentrations in these tissues. Renal and bone lead concentrations have rarely been examined in eagles. We examined relationships among hepatic, renal, and bone lead concentrations in bald and golden eagles from the Canadian prairie provinces. Hepatic and renal lead concentrations were strongly related (R2 = 0.87) while those in liver and bone were significantly but poorly related (R2 = 0.22). Renal lead concentrations of 5 and 18 microg x g-1 (dry weight) corresponded to hepatic lead concentrations of 6 and 30 microg x g-1, the hepatic concentrations that we used as criterion levels associated with elevated lead exposure and death from lead poisoning, respectively. Lead was elevated in 19 of 119 and 21 of 109 liver and kidney samples, respectively. Of these 19 and 21 liver and kidney samples, 14 and 11, respectively, had lead concentrations compatible with death from lead poisoning. Taken together, lead concentrations were elevated in liver or kidney samples from 25 eagles and were compatible with death from lead poisoning in 15. Mean bone lead was higher in eagles with elevated hepatic lead than in those exhibiting background hepatic lead concentrations. However, even in the former group, bone lead concentrations were lower than those in lead-exposed individuals of other species of birds. Bone is probably not a useful tissue for identifying elevated lead exposure in eagles. Three of eleven birds that had been shot had anomalous renal lead concentrations, suggestive of contamination by residue from lead ammunition. It is important to exclude such birds when assessing lead exposure.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p267.html

Echinorhynchus brayi n. sp. (Acanthocephala: Echinorhynchidae) from Pachycara crassiceps (Roule) (Zoarcidae), a deep-sea fish.

Echinorhynchus brayi n. sp. (Palaeacanthocephala: Echinorhynchidae) is described from Pachycara crassiceps (Roule) (Zoarcidae) from the Porcupine Seabight, Northeast Atlantic. The new species closely resembles E. canyonensis Huffman & Kliever, 1977, a parasite of a Pacific zoarcid, but has longer lemnisci, larger eggs and larger testes. E. brayi n. sp. can be readily differentiated from the ten other Echinorhynchus spp. recorded from deep-sea fishes (E. abyssicola, E. gadi, E. longiproboscis, E. malacocephali, E. melanoglaeae, E. muraenolepisi, E. petrotschenkoi, E. sebastolobi, E. trachyrinci and E. truttae), because it has fewer hooks per longitudinal row.

A comparison of blood lead levels in bald eagles from two regions on the great plains of North America.

The connection between bald eagles (Haliaeetus leucocephalus) and the consumption of waterfowl, lead shotshell pellet ingestion, and subsequent lead exposure is well documented in the United States and is presumed also to be widespread in Canada. We compared blood lead concentrations in samples from bald eagles ranging in age from 0.5- to 1.5-yr-old at Galloway Bay, Saskatchewan, Canada (n = 97) during October-November, 1992-95 and Hauser Lake, Montana, USA (n = 81) during October-December, 1990-94, within the Great Plains region of North America. Abundant prey are available in the form of hunter-injured waterfowl in Saskatchewan and spawning salmon in Montana; both areas attract large numbers of mid-continent bald eagles during fall migration. Blood lead concentrations suggestive of recent lead exposure (> 0.201 microgram/ml) were found in 32% and 8% of eagles at Hauser Lake and Galloway Bay, respectively, when samples from each study area were analyzed independently at two laboratories. To determine if this difference was an artifact of interlaboratory variation, we determined a correction factor by reanalyzing 14 Saskatchewan blood samples at each laboratory and predicted blood lead concentrations from Hauser Lake had the samples been analyzed at the Canadian laboratory. Adjusted blood lead concentrations of samples from Hauser Lake indicated that 21% of eagles were recently exposed to lead, a proportion not significantly different from the proportion of the same exposure category at Galloway Bay. Our data do not support the supposition that a large proportion of bald eagles feeding on waterfowl in areas of high hunting pressure will be exposed to lead via consumption of lead shotshell pellets in waterfowl.

Fate of carbofuran and its effects on aquatic macroinvertebrates in Canadian prairie parkland ponds.

: A multipond study was conducted in 1986 to determine the fate of carbofuran and its effects on aquatic macroinvertebrates in alkaline, Canadian prairie parkland ponds. Four ponds were sprayed with carbofuran in late July; four other ponds served as controls. Sixteen hours after spraying, concentrations of carbofuran in the water column ranged from 9-32 µg l(-1). After 124 h, concentrations had declined to 3-12µg l(-1). Carbofuran partitioned into submersed aquatic plants, ranging from three to 46 times greater in the plants than in the surrounding water. Carbofuran was below detection limits in most sediment samples. Among the aquatic macroinvertebrates considered in this study, the crustacean Hyalella azteca and trichopteran larvae declined significantly in abundance following the application of carbofuran. Coenagrionidae and small chironomid larvae did not decline following carbofuran application. Hyalella azteca abundance remained relatively low in treatment ponds through to May 1987, while trichopteran larval abundance had recovered by August 1986. There were no readily apparent shifts in community structure in this study, although slight, disproportionate increases in Chironominae and Coenagrionidae in the treatment ponds following spraying may have resulted from such factors as reduced competition or a change in the size or composition of the food base.