Walter Goessler

Arsenic species in an arsenic hyperaccumulating fern, Pityrogramma calomelanos: a potential phytoremediator of arsenic-contaminated soils

The fern Pityrogramma calomelanos is a hyperaccumulator of arsenic that grows readily on arsenic-contaminated soils in the Ron Phibun district of southern Thailand. P. calomelanos accumulates arsenic mostly in the fronds (up to 8350 microg As g(-1) dry mass) while the rhizoids contain the lowest concentrations of arsenic (88-310 microg As g(-1) dry mass). The arsenic species in aqueous extracts of the fern and soil were determined by high performance liquid chromatography coupled to an inductively coupled plasma mass spectrometer (HPLC-ICPMS) which served as an arsenic specific detector. Only a small part of the arsenic (6.1-12%) in soil was extracted into water, and most of this arsenic (> 97%) was present as arsenate. The arsenic in the fern rhizoids was approximately 60% water-extractable, 95% of which was present as arsenate. In contrast, arsenic in the fern fronds was readily extracted into water (86-93%) and was present mainly as arsenite (60-72%) with the remainder being arsenate. Methylarsonate and dimethylarsinate were detected as trace constituents in only two fern samples. Preliminary estimates of phytoremediation potential suggest that P. calomelanos might remove approximately 2% of the soil arsenic load per year. With due consideration to the type of arsenic compounds present in the fern, and their water-solubility, the option of disposing high arsenic ferns at sea is raised for discussion.

Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study

Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r = 0.84, p < 0.001), whereas the correlation coefficient was much lower in white matter (r = 0.27, p < 0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation.

Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study

PURPOSE To investigate the relationship between transverse relaxation rates R2 and R2*, the most frequently used surrogate markers for iron in brain tissue, and chemically determined iron concentrations. MATERIALS AND METHODS This study was approved by the local ethics committee, and informed consent was obtained from each individuals next of kin. Quantitative magnetic resonance (MR) imaging was performed at 3.0 T in seven human postmortem brains in situ (age range at death, 38-81 years). Following brain extraction, iron concentrations were determined with inductively coupled plasma mass spectrometry in prespecified gray and white matter regions and correlated with R2 and R2* by using linear regression analysis. Hemispheric differences were tested with paired t tests. RESULTS The highest iron concentrations were found in the globus pallidus (mean ± standard deviation, 205 mg/kg wet mass ± 32), followed by the putamen (mean, 153 mg/kg wet mass ± 29), caudate nucleus (mean, 92 mg/kg wet mass ± 15), thalamus (mean, 49 mg/kg wet mass ± 11), and white matter regions. When all tissue samples were considered, transverse relaxation rates showed a strong linear correlation with iron concentration throughout the brain (r² = 0.67 for R2, r² = 0.90 for R2*; P < .001). In white matter structures, only R2* showed a linear correlation with iron concentration. Chemical analysis revealed significantly higher iron concentrations in the left hemisphere than in the right hemisphere, a finding that was not reflected in the relaxation rates. CONCLUSION Because of their strong linear correlation with iron concentration, both R2 and R2* can be used to measure iron deposition in the brain. Because R2* is more sensitive than R2 to variations in brain iron concentration and can detect differences in white matter, it is the preferred parameter for the assessment of iron concentration in vivo.

Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms.

Background There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. Objectives Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. Methods We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). Results The results show that the M287T (T→C) polymorphism in the AS3MT gene, the A222V (C→T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 μg/L arsenic in urine. Females < 60 years of age had, in general, higher methylation efficiency than males, indicating an influence of sex steroids. That might also explain the observed better methylation in overweight or obese women, compared with normal weight men. The influence of the M287T (T→C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. Conclusions The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic.

Plasmapheresis reverses all side-effects of a cisplatin overdose – a case report and treatment recommendation

BackgroundCisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death.Case presentationWe report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m2 of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae.ConclusionTo date, no general accepted guidelines for the treatment of cisplatin overdoses are available. Along with the experience from other published cases, our report shows that plasmapheresis is capable of lowering cisplatin plasma and serum levels efficiently. Therefore, plasma exchange performed as soon as possible can ameliorate all side effects of a cisplatin overdose and be a potential tool for clinicians for treatment. However, additional intensive supportive treatment-modalities are necessary to control all occurring side effects.

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR‐based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.

Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study.

BACKGROUND Long-term exposure to high levels of arsenic is associated with increased risk for cardiovascular disease, whereas risk from long-term exposure to low to moderate arsenic levels (< 100μg/L in drinking water) is unclear. OBJECTIVE To evaluate the association between long-term exposure to low to moderate arsenic levels and incident cardiovascular disease. DESIGN Prospective cohort study. SETTING The Strong Heart Study baseline visit between 1989 and 1991, with follow-up through 2008. PATIENTS 3575 American Indian men and women aged 45 to 74 years living in Arizona, Oklahoma, and North and South Dakota. MEASUREMENTS The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of long-term arsenic exposure. Outcomes were incident fatal and nonfatal cardiovascular disease. RESULTS A total of 1184 participants developed fatal and nonfatal cardiovascular disease. When the highest and lowest quartiles of arsenic concentrations (> 15.7 vs. < 5.8 μg/g creatinine) were compared,the hazard ratios for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for sociodemographic factors, smoking, body mass index, and lipid levels were 1.65 (95%CI, 1.20 to 2.27; P for trend < 0.001), 1.71 (CI, 1.19 to 2.44; P for trend < 0.001), and 3.03 (CI, 1.08 to 8.50; P for trend = 0.061),respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (CI,1.09 to 1.59; P for trend = 0.002), 1.30 (CI, 1.04 to 1.62; P for trend = 0.006), and 1.47 (CI, 0.97 to 2.21; P for trend = 0.032).These associations varied by study region and were attenuated after further adjustment for diabetes, hypertension, and kidney disease measures. LIMITATION Direct measurement of individual arsenic levels in drinking water was unavailable. CONCLUSION Long-term exposure to low to moderate arsenic levels was associated with cardiovascular disease incidence and mortality.

Cadmium exposure and incident cardiovascular disease.

Background: Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort. Methods: We conducted a prospective cohort study of 3348 American Indian adults 45–74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989–1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008. Results: The geometric mean cadmium level in the study population was 0.94 &mgr;g/g (95% confidence interval [CI] = 0.92–0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21–1.70) and 1.34 for coronary heart disease mortality (1.10–1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11–1.38), 1.22 (1.08–1.38), 1.75 (1.17–2.59), and 1.39 (1.01–1.94), respectively. The associations were similar in most study subgroups, including never-smokers. Conclusions: Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor.

Arsenobetaine and other arsenic compounds in the National Research Council of Canada Certified Reference Materials DORM 1 and DORM 2

A silica-based cation-exchange column was used to determine the arsenic compounds in the National Research Council of Canada (NRCC) CRMs DORM 1 and DORM 2 (Dogfish Muscle). With a 20 mM aqueous pyridine mobile phase at pH 3.0, the concentration of arsenobetaine was only 10.7 mg kg–1 As in the extract of DORM 1. When the same extract was chromatographed on an anion-exchange column, 15.9±0.3 mg kg–1 As (arsenobetaine) were found. The calibration for arsenobetaine was linear from 0.5 µg dm–1 As to 10 mg dm–3 As. When the extracts were diluted with water the cation-exchange results approached the anion-exchange results. The multi-element capabilities of ICP-MS allowed the simultaneous monitoring of arsenic and alkali metals. Sodium and potassium were found to co-elute with arsenobetaine. When aqueous solutions of arsenobetaine with 250 mg dm–3 Na were chromatographed, the signal obtained for arsenobetaine was only 60% of the signal without sodium in the solution. When the pH of the 20 mM aqueous pyridine mobile phase was lowered, the alkali metals were separated from arsenobetaine and the results obtained from cation-exchange chromatography were not significantly different from the anion-exchange results. Because DORM 1 is no longer available, the arsenic compounds in DORM 2 were determined. No significant difference was found for the concentration of arsenobetaine (15.6±0.7 mg kg–1 As for DORM 1; 16.0±0.7 mg kg–1 As for DORM 2). The concentrations of the minor arsenic compounds (dimethylarsinic acid, arsenocholine, the tetramethylarsonium cation and an unknown arsenic compound) in DORM 2 were only half the concentrations in DORM 1.

Arsenic exposure in Hungary, Romania and Slovakia

Inorganic arsenic is a potent human carcinogen and toxicant which people are exposed to mainly via drinking water and food. The objective of the present study was to assess current exposure to arsenic via drinking water in three European countries. For this purpose, 520 individuals from four Hungarian, two Slovakian and two Romanian countries were investigated by measuring inorganic arsenic and methylated arsenic metabolites in urine by high performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry. Arsenic in drinking water was determined by atomic absorption spectrometry. Significantly higher concentrations of arsenic were found in both the water and the urine samples from the Hungarian counties (median: 11 and 15 microg dm(-3), respectively; p < 0.001) than from the Slovakian (median: 0.94 and 4.5 microg dm(-3), respectively) and Romanian (median: 0.70 and 2.1 microg dm(-3), respectively) counties. A significant correlation was seen between arsenic in water and arsenic in urine (R(2)= 0.46). At low water arsenic concentrations, the relative amount of dimethylarsinic acid (DMA) in urine was increased, indicating exposure via food. Also, high body mass index was associated with higher concentrations of arsenic in urine (p= 0.03), mostly in the form of DMA. Smokers had significantly higher urinary arsenic concentrations than non-smokers (p= 0.03). In conclusion, elevated arsenic exposure via drinking water was prevalent in some of the counties. Exposure to arsenic from food, mainly as DMA, and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water.