Serum Mg Isotopic Composition Reveals That Mg Dyshomeostasis Remains in Type 1 Diabetes despite the Resolution of Hypomagnesemia.

Hypomagnesemia was historically prevalent in individuals with type 1 diabetes mellitus (T1DM), but contemporary results indicate an incidence comparable to that in the general population, likely due to improved treatment in recent decades, resulting in better glycemic control. However, a recent study found a significant difference between the serum Mg isotopic composition of T1DM individuals and controls, indicating that disruptions to Mg homeostasis persist. Significant deviations were also found in samples taken one year apart. To investigate whether the temporal variability in serum Mg isotopic composition is linked to the transient impact of administered insulin, Mg isotope ratios were determined in serum from 15 T1DM individuals before and one hour after insulin injection/meal consumption using multi-collector inductively coupled plasma-mass spectrometry. Consistent with results of the previous study, significant difference in the serum Mg isotopic composition was found between T1DM individuals and 10 sex-matched controls. However, the average difference between pre- and post-insulin injection/meal T1DM samples of 0.05 ± 0.13‱ (1SD) was not significant. No difference was observed for controls before (-0.12 ± 0.16‱) and after the meal (-0.10 ± 0.13‱) either, suggesting a lack of a postprandial Mg isotopic response within one hour of food consumption, and that the timing of the most recent meal may not require controlling for when determining serum Mg isotopic composition.

Contrasting copper concentrations and isotopic compositions in two Great Lakes watersheds.

Copper (Cu) stable isotopes can elucidate the biogeochemical controls and sources governing Cu dynamics in aquatic environments, but their application in larger rivers and catchments remains comparatively scarce. Here, we use major and trace element hydrogeochemical data, Cu isotope analyses, and mixing modeling, to assess Cu loads and sources in two major river systems in Ontario, Canada. In both the Spanish River and Trent River catchments, aqueous hydrochemical compositions appeared reasonably consistent, but Cu concentrations were more variable spatially. In the Spanish River, waters near (historic) industrial mining activities displayed positive Cu isotope compositions (δ65CuSRM-976 between +0.75 ‰ and +1.01 ‰), but these signatures were gradually attenuated downstream by mixing with natural background waters (δ65Cu -0.65 ‰ to -0.16 ‰). In contrast, Trent River waters exhibited more irregular in-stream Cu isotope patterns (δ65Cu from -0.75 ‰ to +0.21 ‰), beyond the variability in Cu isotope signatures observed for adjacent agricultural soils (δ65Cu between -0.26 ‰ and +0.30 ‰) and lacking spatial correlation, reflective of the more diffuse sourcing and entwined endmember contributions to Cu loads in this catchment. This work shows that metal stable isotopes may improve our understanding of the sources and baseline dynamics of metals, even in large river systems.

The influence of physiological and lifestyle factors on essential mineral element isotopic compositions in the human body: implications for the design of isotope metallomics research.

In the last 20 years, the application of high-precision isotopic analysis of essential mineral elements (Mg, K, Ca, Fe, Cu, and Zn) to biomedicine (sometimes referred to as isotope metallomics) has revealed that their stable isotopic compositions are altered by the metal dysregulation that is fundamental to the pathogenesis of many cancers and other diseases. Despite many published works showing the diagnostic and prognostic potential of this approach, a number of factors that may influence the stable isotopic composition of these essential mineral elements in healthy individuals remain unstudied. In this perspective article, we summarize the available evidence from trophic level studies, animal models, and ancient and modern humans, relating to physiological and lifestyle factors that appear likely (there is evidence indicating their influence) or unlikely (there is evidence indicating their lack of influence) to require controlling for when investigating variations in essential mineral element isotopic compositions in human subjects. We also discuss factors that require additional data to properly assess. There is evidence that sex, menopausal status, age, diet, vitamin and metal supplementation, genetic variation, and obesity influence the isotopic composition of at least one essential mineral element in the human body. The task of investigating potential influences on essential mineral element isotopic compositions in the human body is sizeable, but presents an exciting research opportunity, with each incremental advance helping to improve the quality of research output in the context of isotope metallomics.

Uranium: an overview of physicochemical properties, exposure assessment methodologies, and health effects of environmental and occupational exposure.

Uranium is chemo- and radiotoxic element which can cause multifactorial health hazards. Natural and anthropogenic uranium contamination raises concerns about potential public health problems. Natural contamination plays a significant role with regard to uranium exposure in the general population, whereas anthropogenic contamination leads to occupational uranium exposure, particularly in nuclear industry workers. In this review, we present a state-of-the-art status concerning uranium-induced health risks with a focus on epidemiological findings of uranium processing and enrichment plant workers. We provide a general overview of physicochemical properties of uranium and analytical methods for measuring or monitoring uranium, describe environmental and occupational exposure scenarios, and discuss the challenges for objectively investigating risks from uranium exposure.

Emerging applications of high-precision Cu isotopic analysis by MC-ICP-MS.

As a component of many minerals and an essential trace element in most aerobic organisms, the transition metal element Cu is important for studying reduction-oxidation (redox) interactions and metal cycling in the total environment (lithosphere, atmosphere, biosphere, hydrosphere, and anthroposphere). The "fractionation" or relative partitioning of the naturally occurring "heavy" (65Cu) and "light" (63Cu) isotope between two coexisting phases in a system occurs according to bonding environment and/or as a result of a slight difference in the rate at which these isotopes take part in physical processes and chemical reactions (in absence of equilibrium). Due to this behaviour, Cu isotopic analysis can be used to study a range of geochemical and biological processes that cannot be elucidated with Cu concentrations alone. The shift between Cu+ and Cu2+ is accompanied by a large degree of Cu isotope fractionation, enabling the Cu isotope to be applied as a vector in mineral exploration, tracer of origin, transport, and fate of metal contaminants in the environment, biomonitor, and diagnostic/prognostic marker of disease, among other applications. In this contribution, we (1) discuss the analytical protocols that are currently available to perform Cu isotopic analysis, (2) provide a compilation of published δ65Cu values for matrix reference materials, (3) review Cu isotope fractionation mechanisms, (4) highlight emerging applications of Cu isotopic analysis, and (5) discuss future research avenues.

Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue.

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ66Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g-1 greater than in NAT(MT) (p = 0.00056) and 5.1 µg g-1 greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g-1 greater than in HT (p = 0.00012) and 13.3 µg g-1 greater than in NAT(MT) (p < 0.0001), whereas δ66Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ66Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ66Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (64Zn-rich) expression by activated matrix metalloproteinase (66Zn-rich) in MT, and indicates a resultant 66Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.

Zinc stable isotopes in urine as diagnostic for cancer of secretory organs.

Breast, prostate, and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations [Zn] and Zn stable isotope compositions (δ66Zn) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and δ66Zn in urine from prostate (n = 22), breast (n = 16), and from women with benign breast disease (n = 14) and compared those with age-matched healthy controls (22-49 years or 50+ years) and published data for pancreatic cancer (n = 17). Our results show that cancer-induced changes are reflected in higher urinary [Zn] and lower urinary δ66Zn for pancreatic and prostate cancer and benign breast disease when compared with healthy controls. For prostate cancer, the progression of low [Zn] and high δ66Zn for patients of low-risk disease toward high [Zn] and low δ66Zn for the higher risk patients demonstrates that [Zn] and δ66Zn in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from breast cancer patients shows undistinguishable δ66Zn to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary δ66Zn may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.

Postprandial zinc stable isotope response in human blood serum.

In recent years, considerable advances have been made in the field of medical isotope metallomics, but numerous fundamental physiological processes remain to be investigated. Past studies report that blood serum Zn concentrations decrease by between about 10 and 25%, depending on the size of meal, approximately three hours postprandially (i.e. after eating), before returning to baseline values if no meals are consumed over the following four to five hours. Nine participants were recruited for this study to investigate whether this postprandial Zn concentration decrease is accompanied by a stable isotope response. A baseline serum sample was collected from participants in the morning after overnight fasting. A 576 kcal meal was then provided and additional serum samples were taken 90 and 180 minutes post-meal to coincide with the postprandial response. Serum Zn concentrations decreased postprandially by an average of 21 ± 9% (1SD), but this was not accompanied by a change in stable Zn isotope composition (mean Δ66Zn180-minute-baseline = 0.01 ± 0.09‰, 2SD). We propose that hemodilution and the rapid, efficient postprandial transfer of albumin-bound Zn from serum to the liver and pancreas is responsible for the lack of postprandial serum Zn isotopic response. These results indicate that studies examining solely the distribution of Zn isotopes in serum may obtain samples without considering timing of the most recent meal. However, future studies seeking to compare serum Zn concentrations with δ66Zn values should draw blood samples in the morning after overnight fasting.