Anthony Polwart

Elevated urinary excretion of aluminium and iron in multiple sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system of as yet unknown aetiology. A consensus of opinion has suggested that the disorder is the result of an interplay between environmental factors and susceptibility genes. We have used a battery of analytical techniques to determine if the urinary excretion of i) markers of oxidative damage; ii) iron and iii) the environmental toxin aluminium and its antagonist, silicon, are altered in relapsing remitting (RRMS) and secondary progressive MS (SPMS). Urinary concentrations of oxidative biomarkers, MDA and TBARS, were not found to be useful indicators of inflammatory disease in MS. However, urinary concentrations of another potential marker for inflammation and oxidative stress, iron, were significantly increased in SPMS (P<0.01) and insignificantly increased in RRMS (P>0.05). Urinary concentrations of aluminium were also significantly increased in RRMS (P<0.001) and SPMS (P<0.05) such that the levels of aluminium excretion in the former were similar to those observed in individuals undergoing metal chelation therapy. The excretion of silicon was lower in MS and significantly so in SPMS (P<0.05). Increased excretion of iron in urine supported a role for iron dysmetabolism in MS. Levels of urinary aluminium excretion similar to those seen in aluminium intoxication suggested that aluminium may be a hitherto unrecognized environmental factor associated with the aetiology of MS. If aluminium is involved in MS then an increased dietary intake of its natural antagonist, silicon, might be a therapeutic option.

Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease

There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimers disease. The null hypothesis which underlies any link is that there would be no Alzheimers disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimers disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimers disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P<0.001) their urinary excretion of silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and concomitantly reduced significantly P=0.037) their urinary excretion of aluminium (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P>0.05) influence upon the urinary excretion of iron (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimers disease.

Brain Burdens of Aluminum, Iron, and Copper and their Relationships with Amyloid-β Pathology in 60 Human Brains

The deposition in the brain of amyloid-β as beta sheet conformers associated with senile plaques and vasculature is frequently observed in Alzheimer’s disease. While metals, primarily aluminum, iron, zinc, and copper, have been implicated in amyloid-β deposition in vivo, there are few data specifically relating brain metal burden with extent of amyloid pathologies in human brains. Herein brain tissue content of aluminum, iron, and copper are compared with burdens of amyloid-β, as senile plaques and as congophilic amyloid angiopathy, in 60 aged human brains. Significant observations were strong negative correlations between brain copper burden and the degree of severity of both senile plaque and congophilic amyloid angiopathy pathologies with the relationship with the former reaching statistical significance. While we did not have access to the dementia status of the majority of the 60 brain donors, this knowledge for just 4 donors allowed us to speculate that diagnosis of dementia might be predicted by a combination of amyloid pathology and a ratio of the brain burden of copper to the brain burden of aluminum. Taking into account only those donor brains with either senile plaque scores ≥4 and/or congophilic amyloid angiopathy scores ≥12, a Cu:Al ratio of <20 would predict that at least 39 of the 60 donors would have been diagnosed as suffering from dementia. Future research should test the hypothesis that, in individuals with moderate to severe amyloid pathology, low brain copper is a predisposition to developing dementia.

Serum CRP-like protein profile in common carp Cyprinus carpio challenged with Aeromonas hydrophila and Escherichia coli lipopolysaccharide.

The potential of C-reactive protein (CRP)-like proteins to be used as a biomarker of health status in cultured carp obtained from various European fish lines has been assessed. Varying CRP-like protein levels in the serum of carp were monitored using an indirect competitive enzyme-linked immunosorbent assay. CRP-like protein basal levels in normal fish varied between carp lines, ranging on average from 2.9+/-0.15 to 12.57+/-1.19 microg ml(-1). Serum levels of CRP-like protein in carp were observed to increase several fold in fish infected with the pathogen Aeromonas hydrophila. However, carp injected with Escherichia coli lipopolysaccharide (LPS) serotype 0111:B4 did not exhibit an increase in CRP-like proteins levels.

Elevated urinary aluminium in current and past users of illicit heroin.

The use of illicit heroin is associated with aberrant neurology of unknown aetiology and various psychiatric illnesses. Aluminium, which is a proven neurotoxin, is present in significant amounts in illicit heroin and may also be volatilized and inhaled following the vaporization of heroin off aluminium foil (‘Chasing the Dragon’). The purpose of this study was to establish if the use of illicit heroin was associated with an increase in the body burden of aluminium. We have used graphite furnace atomic absorption spectrometry to measure the aluminium and iron contents of the urine of current and past users of illicit heroin and used these data to estimate body burdens of aluminium. Urinary excretion of aluminium is the most effective non‐invasive indicator of the body burden of aluminium and was found to be significantly (P < 0.001) higher in users of illicit heroin, range 14–3382 nmol/mmol creatinine (mean ± SD; 222 ± 491 nmol/mmol creatinine), than in a normal non‐drug abusing control population, range 23–74 nmol/mmol creatinine (mean ± SD; 43 ± 19 nmol/mmol creatinine). Exposure to aluminium from the use of illicit heroin may be of particular significance because the urinary excretion of iron, another major contaminant of illicit heroin, in users (mean ± SD; 53 ± 63 nmol/mmol creatinine) was not significantly different (P > 0.05) from the control population (mean ± SD; 38 ± 18 nmol/mmol creatinine). We have shown for the first time that the use of illicit heroin may be a significant contributor to the body burden of aluminium. Further research will be required to determine if adventitious aluminium has a role in heroin use‐related neuropathology and neurology.

The aluminium content of breast tissue taken from women with breast cancer.

The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content in defatted tissue and oil from such tissues and thereby contribute towards our knowledge on aluminium and any role in breast cancer.

X-ray microanalysis (EDXMA) of cadmium-exposed eggs of Bothriocephalus acheilognathi (Cestoda: Bothriocephalidea) and the influence of this heavy metal on coracidial hatching and activity

Over recent years it has been established that pollutants can have a significant impact on host-parasite systems in the aquatic environment, so much so that it has been proposed that parasite fauna may be a useful parameter to monitor water quality. Surprisingly, with perhaps the exception of trematodes and bioaccumulation in adult acanthocephalans, detailed observations on the interaction between helminths, particularly cestodes, and pollutants such as heavy metals, are lacking. In this study, eggs of the carp tapeworm, Bothriocephalus acheilognathi were exposed to a range of cadmium concentrations (0.1, 10, 100 and 10,000 mcirog/L) and coracidial hatching and survival assessed. Results indicated that the egg is highly resistant to heavy metal pollution and hatching occurs even at 10,000 microg/L. In contrast, the activity of the liberated coracidium significantly decreased after 1h exposure to cadmium at 10 and 100 microg/L. Electron microscopic X-ray microanalysis of parasite eggs exposed to 1000 and 10,000 microg/L cadmium revealed that cadmium accumulates on the surface of the egg and does not penetrate detectably into the enclosed coracidium. This means that the parasite eggs may be able to withstand a heavy metal pollutant incident.

Engagement with Online Pre-exam Formative Tests Improves Exam Performance and Feedback Satisfaction

Abstract The National Union of Students (NUS) National Student Experience Report identified examination feedback as an area where students had particular concerns. This finding was echoed in the authors’ institution and triggered an action research project to investigate ways of improving students’ perceptions of pre- and post-exam feedback. We report the results of part of the project aimed at improving student satisfaction with pre-exam feedback and preparedness for the end of module examination, where we used an ‘Assessment for Learning’ (AfL) strategy. Students on a second year human genetics module (LSC-20050) were supplied with a series of 10 formative online tests with instant feedback. Our results show that students who completed more of the online tests performed significantly better in the end of module exam than students who completed < 4 tests. Comparing the LSC-20050 exam results with other bioscience modules indicates that the students who took fewer tests did no better in LSC-20050, but the students who did more tests showed significantly enhanced performance in LSC-20050. Students who did the tests reported that they found the tests a useful way to learn and felt better prepared for the exam. Thus, engagement with online assessments can improve pre-exam feedback satisfaction with the added bonus of improving exam performance.