Biomedical subjects

David B Senn

Publications and source records attributed to David B Senn.

5 recordsLinked to original sources

PubMed2006

Acceleration of amyloid beta-peptide aggregation by physiological concentrations of calcium.

Alzheimer disease is characterized by the accumulation of aggregated amyloid beta-peptide (Abeta) in the brain. The physiological mechanisms and factors that predispose to Abeta aggregation and deposition are not well understood. In this report, we show that calcium can predispose to Abeta aggregation and fibril formation. Calcium increased the aggregation of early forming protofibrillar structures and markedly increased conversion of protofibrils to mature amyloid fibrils. This occurred at levels 20-fold below the calcium concentration in the extracellular space of the brain, the site at which amyloid plaque deposition occurs. In the absence of calcium, protofibrils can remain stable in vitro for several days. Using this approach, we directly compared the neurotoxicity of protofibrils and mature amyloid fibrils and demonstrate that both species are inherently toxic to neurons in culture. Thus, calcium may be an important predisposing factor for Abeta aggregation and toxicity. The high extracellular concentration of calcium in the brain, together with impaired intraneuronal calcium regulation in the aging brain and Alzheimer disease, may play an important role in the onset of amyloid-related pathology.

Alzheimer Disease↗

PubMed2004

Equilibrium-based sampler for determining Cu2+ concentrations in aquatic ecosystems.

The bioavailability of potentially toxic metals in aquatic systems is frequently related to the dissolved free metal ion (M2+) concentration. However, typical methods used to determine M2+ are labor intensive or require sophisticated equipment. We developed an inexpensive, in situ sampling device--the "gellyfish"--that simplifies Cu2+ determinations in seawater. The gellyfish is a thin disk of polyacrylamide gel embedded with iminodiacetate (Id) groups bound to immobile beads. The sampler operates on the principle that the immobilized Id groups equilibrate with the Cu2+ concentration of the surrounding solution. Cu is then back-extracted into a known volume of 10% HNO3 and measured by inductively coupled plasma mass spectrometry (ICP-MS). In laboratory tests, we varied Cu2+ concentrations between 10(-12) and 10(-8) M and salinity between 5 and 35 ppt. Id-bound Cu (CuId(measured)) did not respond to changes in total Cu. However, CuId(measured) does increase in a predictable manner with increasing Cu2+, and prototype gellyfish precision (average coefficient of variation = 10%) is sufficient to resolve small differences in Cu2+ (+/-30%). Modeled Cu uptake, based on thermodynamic equilibrium speciation of Id within gellyfish, is a good predictor of CuId(measured) (r2 = 0.96 and n = 45).

Acrylic Resins↗

PubMed2004

Antimony: an unlikely confounder in the relationship between well water arsenic and health outcomes in Bangladesh.

Recent in vitro studies have suggested a potential role for antimony as a confounder in human health studies related to arsenic in drinking water. We measured tube-well water concentrations of antimony and arsenic in the Pabna region of Bangladesh, where arsenic concentrations are known to be elevated and the concentrations of antimony have not yet been thoroughly documented. Two hundred forty-five tube-well water samples were collected from various regions in Pabna, Bangladesh, as part of an ongoing case-control study. Water samples were analyzed for arsenic and antimony concentrations by inductively coupled plasma-mass spectrometry using U.S. Environmental Protection Agency method 200.8. The arsenic concentrations in the tube-well water samples ranged from < 1 microg/L to 747 microg/L. All 245 water samples had antimony concentrations < 1 microg/L. Based on consideration of the concentrations used the in vitro studies compared with field-observed concentrations, our results do not support the hypothesis that antimony would be a significant confounder in observed relationships between arsenic exposure through drinking water and potential health outcomes in Pabna, Bangladesh.

Antimony↗

PubMed2004

Particulate arsenic and iron during anoxia in a eutrophic, urban lake.

The bioavailability and transport of particle-reactive pollutants are influenced by their partitioning between dissolved and particulate phases. We explored the importance of particle complexation to the arsenic cycle in an urban lake (Upper Mystic Lake, eastern MA, USA) that experiences arsenic remobilization from contaminated sediments during seasonal hypolimnetic anoxia. Particle size distributions were measured using a new in situ serial filtration system that excludes oxygen and filters at low flow rates to minimize filtration artifacts. Despite anoxia, the majority of remobilized As was present as As(V), and typically 85 to 95% of total As was particle complexed, with 25 to 50% found in the size fraction between 0.4 and 0.05 microm. Iron was distributed similarly among these size classes (>95% of total Fe associated with particles larger than 0.05 microm, 30 to 50% between 0.4 microm and 0.05 microm), contrary to conventional expectation that the majority of Fe should be present as soluble Fe(II) in anoxic waters. By classical filtration (i.e., through a 0.4-microm filter), the colloidal fractions of both Fe and As would have been inaccurately classified as dissolved. Correlations between depth profiles of total As and particulate Fe as well as comparisons of measured arsenic sorption (i.e., total As > 0.05 microm) against predictions by surface complexation modeling of As on amorphous Fe(III) oxides argue that arsenic sorbed on Fe(III) oxides was the major As species present in this lake's hypolimnion throughout several months of anoxia.

Arsenic↗

PubMed2002

Nitrate controls on iron and arsenic in an urban lake.

Aquatic ecosystems are often contaminated by multiple substances. Nitrate, a common aquatic pollutant, strongly influenced the cycling of arsenic (As) under anoxic conditions in urban Upper Mystic Lake (Massachusetts, USA) by oxidizing ferrous iron [Fe(II)] to produce As-sorbing particulate hydrous ferric oxides and causing the more oxidized As(V), which is more particle-reactive than As(III) under these conditions, to dominate. This process is likely to be important in many natural waters.

Anaerobiosis↗