Hepatic and renal histology and mercury concentrations of North West and North East Greenland narwhals (Monodon monoceros)

Narwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males). The zoological length was significantly larger and hepatic and renal concentrations significantly higher in adults compared to subadults. When comparing tissues, the Hg levels were significantly the highest in liver, while a correlation between metal levels in liver and kidneys was positive and significant. Histological examination of renal tissues presented four types of glomerular lesions (capillary dilatation [0–100%], membrane thickening [0–100%], dilatation of space [0–80%], and sclerosis [0–70%]) and two tubular lesions (atrophy/hyalinization [0–40%] and casts [0–60%]). Hepatic tissues exhibited three portal lesions (fibrosis [0–33%], cell infiltrates [0–40%], and bile duct proliferation [0–40%]) and two parenchymal lesions (steatosis [83–100%] and lipid-filled Ito cells [0–33%]). All 12 lesions were found in adult whales from North West Greenland while eight were present in adult whales from North East Greenland. Six lesions were detected in subadults from North East Greenland and four in subadults from North West Greenland. A significantly higher frequency of dilatation and hyalinization of Bowman’s space and capsule and glomerular capillary dilatation was found in adult narwhals from West Greenland. There was no marked difference in Hg concentrations in whales with and without histological lesions. In conclusion, the prevalence of histological changes and Hg levels were the highest in adults and therefore both age and metal are important factors to include when evaluating liver and kidney lesions in narwhals.     

Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose‐dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5‐fold higher) than that needed to obtain 29 nmol/L of HgCl₂ on the vascular function. Three‐month‐old male Wistar rats received intramuscular (i.m.) HgCl₂ for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l ‐NAME (100 μmol/L). The phosphorylated‐eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE‐induced contractions, while l ‐NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase‐2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin‐angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.     

Comparative assessment of blood mercury in American alligators (Alligator mississippiensis) from Coastal North Carolina and Florida

Ecotoxicology - Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis)...     

Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil

It has been suggested that docosahexaenoic acid (DHA) or other n-3 polyunsaturated fatty acids (PUFAs) may prevent or ameliorate methyl mercury's neurotoxicity. To examine interactions between PUFAs and methyl mercury exposure, sixty-six female Long-Evans rats were exposed to methyl mercury continuously via drinking water from fifteen weeks of age. Water included methyl mercury concentrations of 0, 0.5, and 5.0 ppm, creating estimated intakes of about 0, 40, and 400 microg/kg/day across exposure groups. An additional fifty-eight female offspring were exposed to methyl mercury only during gestation. Rats consumed one of two diets, each based on AIN-93 formulation, providing a 2 (generation) X 2 (diet) X 3 (methyl mercury exposure) factorial experimental design. A "coconut oil" diet (1/3 of fats were provided by coconut oil) was marginally adequate in n-3 PUFAs and contained no DHA. A "fish oil" diet was rich in n-3 fatty acids, including DHA. The diets were approximately equal in n-6 fatty acids. Forelimb grip strength declined with age for all groups, but the decline was greatest for those exposed chronically to 400 microg/kg/day of methyl mercury. This high-dose group also displayed hind limb crossing, gait disorders, and diminished running wheel activity. Dietary n-3 fatty acids did not influence these effects. Chronic exposure to 400 microg/kg/day of methyl mercury resulted in blood and brain concentrations of about 70 and 10 ppm, respectively, approximately 50-fold higher than concentrations seen in rats exposed to 40 microg/kg/day. Rats that became ill and died before the experiment ended had higher concentrations of mercury than their cohorts who survived to the end. Organic mercury was highly correlated with total mercury in these rats but inorganic mercury remained approximately constant. Some deaths were due to urolithiasis (kidney or bladder stones) associated with a dietary contaminant and that was eventually fatal to 22% of the females in the colony. Neurobehavioral effects are reported on rats that did not become ill.     

Setting standards of practice in therapeutic drug monitoring and clinical toxicology: a North American view

Standards for therapeutic drug monitoring (TDM) must address the factors required for a valid TDM result. These are that the test be ordered with an appropriate indication, samples be obtained at the appropriate time, analysis be precise and accurate, and the result be interpreted and used correctly. General indications for ordering drug concentrations are to assess patient compliance, lack of response, adverse effects, initial or new baseline concentration after steady state has been achieved, and drug interactions. In establishing standards for clinical toxicology testing, the following points need to be considered: relatively few drugs will be involved in the majority of overdoses in a given location, the majority of drug overdoses and poisonings are treated symptomatically and supportively, and there are a relatively small number of drugs the testing of which may provide useful information in the emergency setting. An effective toxicology screen can be designed by first developing a list of candidate drugs that have antidotes, require specific treatment, are frequently encountered, or have a delayed onset of toxicity. Once such a list is in hand, it can be further evaluated to determine whether qualitative or quantitative testing is most appropriate and if rapid, convenient methods of analysis are available.     

Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial

Olanzapine is an atypical antipsychotic that is effective in the treatment of schizophrenia. Olanzapine plasma concentrations > or = 9.3 ng/mL (24 hours postdose) have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanzapine concentrations and treatment response from the North American Double-Blind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meeting DSM-III-R criteria for schizophrenia were randomly assigned to receive olanzapine, haloperidol, or placebo. Patients who were randomly assigned to receive olanzapine were given daily doses ranging from 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma concentrations were obtained between 10 and 16 hours (11.7 +/- 1.7 hours) after the last dose was administered. Therapeutic response data and olanzapine concentrations used for analysis were obtained from the endpoint visit for each patient if the patient had been receiving a fixed olanzapine dose for at least the last 2 weeks of the study. Plasma concentrations from previous visits were used if endpoint concentrations were invalid. Response was defined as a > or = 20% reduction in Brief Psychiatric Rating Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity scale score of < or = 3 or a final BPRS score of < or = 35. The final ROC analysis included data from 84 patients and suggested an olanzapine concentration > or = 23.2 ng/mL to be a predictor of therapeutic response. Fifty-two percent of patients with 12-hour olanzapine concentrations > or = 23.2 ng/mL responded, whereas only 25% of patients with concentrations < 23.2 ng/mL responded. Furthermore, an olanzapine concentration > or = 23.2 ng/mL was a predictor of response in the Scale for the Assessment of Negative Symptoms (> or = 20% decrease and endpoint CGI < or = 3). Olanzapine concentrations were found to be a function of olanzapine dose (in milligrams per day) and gender such that prospective olanzapine dosing is feasible. A 12-hour olanzapine plasma concentration of > 23.2 ng/mL was a predictor of therapeutic response in acutely ill patients with schizophrenia. Males required a higher olanzapine dose to reach this threshold concentration than their female counterparts.     

Validity of methyl mercury hair analysis: mercury monitoring in human scalp/nude mouse model

OBJECTIVE: The grafting of human scalp hair was used as a new application of this method to explore methyl mercury incorporation into human hair and to validate this model for mercury monitoring in hair. METHODS: Human scalp grafts were transplanted to athymic BALB/c nude mice. The animals were exposed to methyl mercury either as a single dose i.p. or continuously for 4 months, using ALZET osmotic pumps. The mercury concentration in hair was determined using x-ray fluorescence (XRF) spectrometry by segmental (2 mm) analysis of a single strand, and tissue concentrations were measured by cold vapor atomic absorption analysis. RESULTS: Human scalp hair grown in nude mice showed long-term persistence of human features including the expression of histocompatibility antigens (KAB 3, W 6/32, SF 1-1.1.1) and normal hair morphometry. The disposition of methyl mercury in nude mice followed a one-compartment model with a whole body elimination half-life of 6.7 days (elimination constant, k = 0.1/day). Autoradiographic studies revealed that methyl mercury was rapidly incorporated into areas of the hair follicle undergoing active keratinization. Methyl mercury concentrations in human hair transplanted onto nude mice were two orders of magnitude higher than in blood and attained a mean hair: blood ratio of 217 : 1, similar to ratios reported only in human studies. CONCLUSIONS: This study demonstrated that human hair grown on nude mice can record the level of exposure to methyl mercury and can serve as a valuable research tool to study mercury incorporation into human hair.     

A sensitive new method for clinically monitoring cytarabine concentrations at the DNA level in leukemic cells

Cytarabine (ara-C), a major antileukemic agent, is phosphorylated in the cell to cytarabine triphosphate (ara-CTP), which is then partly incorporated into DNA. The drug incorporation into DNA poisons the extending primer against further incorporation of deoxyribonucleotides including dCTP, ultimately inhibiting DNA synthesis. While intracellular ara-CTP concentration has been found to predict clinical outcome, cytotoxicity in vitro is determined primarily by the extent of drug incorporation into DNA. However, clinically appropriate quantitation methods for ara-C at the DNA level have not been available. We developed a sensitive new method for monitoring ara-C incorporated into DNA in vivo. After DNA from leukemic cells was fractionated using the Schmidt-Thannhauser-Schneider method, it was degraded to constituent nucleosides to release ara-C, which was isolated from the nucleosides using HPLC and then measured by radioimmunoassay. Recovery for DNA fractionation, ara-C release by degradation, and ara-C isolation were 92.0+/-6.4%, 90.7+/-9.4%, and 98.5+/-1.4%, respectively. The method was found to determine ara-C incorporation into DNA of ara-C-treated HL 60 cells in vitro with minimal interassay variation. The values determined were compatible with those determined by scintillation counting in parallel experiments using tritiated ara-C. Our method could be used to monitor DNA-incorporated ara-C concentrations during ara-C therapy, together with plasma ara-C and intracellular ara-CTP concentrations. ara-C incorporation into DNA appeared to be associated with intracellular retention of ara-CTP or persistence of plasma ara-C. Thus, the present method is sensitive, accurate, precise, and may permit therapeutic drug monitoring at the DNA level for better individualization of antileukemic regimens.     

Manchineel dermatitis in North American students in the Caribbean

We report an outbreak of Manchineel dermatitis and ophthalmitis in four students from North America who visited the island of Bequia, West Indies. The exposure resulted from taking shelter during a rain storm under a Manchineel tree. Manchineel exposure and ingestion can lead to severe and even fatal disease.     

Differential trends in mercury concentrations in double-crested cormorant populations of the Canadian Prairies

Mercury and selenium concentrations were measured in double-crested cormorants (Phalacrocorax auritus), piscivorous fish, and common prey items in five lakes in two ecoregions in Saskatchewan, Canada. Hg and Se concentrations in cormorants were within the natural ranges of birds living in un-impacted sites. Site explained a significant proportion of the variation in total Hg (THg) and methylmercury (MeHg) concentrations in both cormorant breast muscle and livers. Birds nesting on more northern lakes in the Boreal Plain ecoregion (THg range 0.11–1.06 and 0.26–9.27 μg g^?1 wet weight, for breast and liver respectively) had lower THg concentrations compared to those from lakes in the Prairie ecoregion (THg range 0.60–4.26 μg g^?1 ww and 1.59–25.11 μg g^?1, for breast and liver respectively). Concentrations of MeHg in livers was also lower in birds from northern sites (0.06–1.15 μg g^?1 ww) compared to those from prairie sites (0.22–4.06 μg g^?1 ww). We documented a wide range of %MeHg in livers (4.5–52 %), indicative of detoxifying MeHg via demethylation to inorganic Hg. Our data suggest that the threshold value where demethylation rates increase substantially appears to be ~10 μg g^?1 ww MeHg, similar to thresholds in other wildlife. Molar ratios of Hg:Se suggests that some birds from highly saline Reed Lake in the prairie region had insufficient Se available to bind to Hg, thereby removing Se binding as a mitigative strategy for high Hg levels for these birds.     

Temporal and spatial changes in mercury concentrations in the North Atlantic as indicated by museum specimens of glacier lanternfish Benthosema glaciale (Pisces: Myctophidae)

Museum specimens of glacier lanternfish Benthosema glaciale were used to investigate long-term variations in mercury concentration of mesopelagic organisms from the North Atlantic. B. glaciale is an abundant mesopelagic fish species in the boreal and sub-polar pelagic regions of the North Atlantic, playing an important role in the cycling of energy in the oceanic food webs of these systems. We used 35 museum specimens of lanternfish, collected from the Gulf Stream biogeographic region between 1936 and 1993, to test for long-term variations in mercury concentrations. In addition, we studied the mercury concentrations throughout the geographical range of the species, using 105 specimens collected around 1970s. Mercury concentrations were similar over time; however there was evidence of a noteworthy increase in mercury contamination during the World War II (1941) followed by a general decrease with lowest concentrations being found in 1954 and 1993. Significant differences were found between the different studied areas, probably reflecting different degrees of anthropogenic contamination. The results presented here indicate that museum myctophids may be suitable for the assessment of historical changes in mercury contamination of marine ecosystems.     

Opium poppy monitoring with remote sensing in North Myanmar

Background

Myanmar has long been a focus of the international community as a major opium poppy cultivation region.

Method

This study used remote sensing technology and ground verification to monitor opium poppy cultivation for three opium poppy growth seasons in North Myanmar.

Results

The study found that opium poppy cultivation has remained high. In 2005-6, 2006-7 and 2007-8 growing seasons the total areas monitored were 52,482 km², 178,274 km² and 236,342 km² and the total cultivated area of opium poppy was 8959 ha, 18,606 ha and 22,300, respectively. This was significantly less than cultivation levels reported during the 1990s. The major cultivation regions were located in Shan State, producing 88% of total poppy cultivation in North Myanmar in 2007-8. The opium poppy was mainly cultivated in the interlocking regions controlled by the local armed forces in Shan State. The field survey noted that most households in this area were poor and poppy cultivation was a main source of income. There were also differences between our figures on poppy cultivation and those reported by United Nations Office on Drugs and Crime.

Conclusion

Our study shows that although the opium poppy cultivation in North Myanmar has reduced over recent years, it remains a major producer of opium and to which the international community needs to pay attention, especially in those areas controlled by local armed forces.     

Small concentrations of mercury enhances positive inotropic effects in the rat ventricular myocardium

Small concentrations of mercury reduce the force development of the rat right myocardium and inhibit the sodium pump. This inhibition might increase the amount of activator Ca(2+) in the sarcoplasmic reticulum available upon activation. We further investigated whether this action could potentiate positive inotropic effects produced by Ca(2+) increment (0.62-1.25mM) and isoproterenol (20nM). Right ventricular strips contracting isometrically were treated with 0.1 and 1μM HgCl(2). Results showed that after HgCl(2) treatment the magnitude of both inotropic interventions was increased. Considering that Hg(2+) amongst its effects induces hypertension and might be associated with cardiovascular diseases these potentiating effects might have hazardous consequences.     

Factors influencing exposure of North American river otter (Lontra canadensis) and American mink (Neovison vison) to mercury relative to a large-scale reservoir in northern British Columbia,Canada

Although reservoir creation increases fish mercury (Hg) concentrations, little information exists on its effects on Hg concentrations in aquatic mammals. River otters (Lontra canadensis) and American mink (Neovison vison) are two aquatic mammals that have been used as model species for assessing Hg bioaccumulation in aquatic systems. We assessed Hg and selenium (Se) concentrations in these two species within and outside of the Williston Reservoir (Peace-Williston (PW) watershed) in northern British Columbia (BC) and used these data to investigate potential explanatory factors (i.e., watershed, gender, trophic level (δ15N), and regional geology) influencing Hg concentrations. Hg concentrations in otter and mink inhabiting the Mackenzie watershed (outside the PW) were significantly lower than other watersheds in Northern BC. The general trend was the same for both species; the Peace-Williston having the highest and Mackenzie having the lowest Hg concentrations. For mink, the Peace-Williston watershed, higher trophic levels, and higher proportions of igneous/metamorphic bedrock were all significant influences on higher Hg concentrations (logistic regression). Higher trophic levels or proportions of of igneous/metamorphic bedrock, however, were not directly associated with the PW watershed suggesting there may be an impoundment effect. Baseline data on natural Hg inputs before planned anthropogenic changes occur is a critical first step to aiding interpretations of Hg-related effects on wildlife populations and their related ecosystems.

     

Using nestling feathers to assess spatial and temporal concentrations of mercury in bald eagles at Voyageurs National Park, Minnesota, USA

Bald eagles (Haliaeetus leucocephalus) have been utilized as a biosentinel of aquatic ecosystem health in the Great Lakes Region since the early 1960s. Bald eagle populations have been monitored at Voyageurs National Park (VNP), Minnesota, since 1973. For the past 20 years, researchers have collected feathers from nestling bald eagles to assess their dietary exposure to mercury (Hg) on Rainy, Kabetogama, and Namakan lakes in VNP. Mercury is an environmental pollutant with both natural and anthropogenic sources, and negatively affects many species of wildlife. In a previous study, geometric mean concentrations of Hg in feathers of nestling bald eagles were greater at VNP (20 mg/kg Dry Weight (DW)) than in nestling feathers from other Great Lakes subpopulations (~7 mg/kg DW), for the period 1985–1989. Current geometric mean concentrations have declined by 77.4% since 1989 at VNP. While all samples from 1985 to 1989 had detectable concentrations of Hg, 10% of current samples had concentrations below the reportable detection limit (0.001 mg/kg DW, n = 180). The major lakes at VNP are impounded, and Hg concentrations also declined greatly after the lake level stabilization order by the International Joint Commission was implemented in 1999. Mercury concentrations in feathers of nestling bald eagles from 1989 to 2010 ranged from ND (<0.001) to 34.97 mg/kg DW. The highest single concentration in a nestling was from Namakan Lake in 2010. The five-year geometric means for Rainy, Kabetogama, and Namakan lakes for 2006–2010 were 6.08, 1.07, and 5.56 mg/kg DW (n = 28, n = 32, n = 27) respectively. Although Hg concentrations in feathers of nestlings greatly declined after the change in water level management in 1999 and are lower than 1989 concentrations, recent samples suggest a gradual increase. Continued monitoring of nestling feather concentrations will be essential to assess this increase, to determine the source of Hg, to determine if there are changes to methylation potential, and to evaluate and optimize water level management.