scholarly journals Resolving Whether Inhalation of Depleted Uranium Contributed to Gulf War Illness Using High-Sensitivity Mass Spectrometry

2020 ◽  
Author(s):  
Randall Parrish ◽  
Robert Haley

Abstract Background: Of the hypothesized causes of Gulf War Illness (GWI), a chronic multi-symptom illness afflicting approximately 25 percent of >700,000 military personnel deployed to the 1991 Gulf War, depleted uranium (DU) and exposure to nerve agents have stimulated the most intense international concern. Past depleted uranium research on Gulf War veterans has measured urinary uranium concentration [U] and uranium isotopic ratios with low precision mass spectrometry primarily in GW veterans with retained shrapnel but has not used high precision mass spectrometry to test for an association of GWI with inhaled DU and we set out to test this potential association. Methods: We applied a standard biokinetic model to predict the urinary total [U] and uranium isotopic ratios in urine 18 years after inhalation exposure. We applied high sensitivity mass spectrometry methods capable of detecting the predicted levels in 154 individuals of a population-representative sample of U.S. veterans in whom Gulf War illness had been determined by standard case definitions and DU inhalation exposures obtained by medical history. Results: Methods used in past studies are capable of detecting only the high urinary uranium excretion levels from retained DU shrapnel but not lower levels predicted from DU inhalation. Using high precision mass spectrometry, we found no difference in the 238U/235U ratio in veterans meeting the standard case definitions of GWI versus control veterans, and no differences by levels of DU inhalation exposure. Our bivariate analysis of 236U/238U by 235U/238U showed only the signature of natural dietary uranium, excluding DU inhalation exposures above 0.4 mg, far below the disease-causing threshold. Conclusion: The findings by high precision mass spectrometry support the conclusion that even the highest levels of DU inhalation played no role in the development of Gulf War illness. Other factors including exposure to aerosolized organophosphate compounds (pesticides and sarin nerve agent) remain as the most likely cause(s) of GWI.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Randall R. Parrish ◽  
Robert W. Haley

AbstractOf the hypothesized causes of Gulf War Illness (GWI), a chronic multi-symptom illness afflicting approximately 25% of military personnel deployed to the 1991 Gulf War, exposure to depleted uranium (DU) munitions has attracted international concern. Past research has not tested the potential association of GWI with inhaled DU nor used isotope mass spectrometry of sufficient sensitivity to rigorously assess prior DU exposure. We applied a standard biokinetic model to predict the urinary concentration and uranium isotopic ratios for a range of inhalation exposures. We then applied sensitive mass spectrometry capable of detecting the predicted urinary DU to 154 individuals of a population-representative sample of U.S. veterans in whom GWI had been determined by standard case definitions and DU inhalation exposures obtained by medical history. We found no difference in the 238U/235U ratio in veterans meeting the standard case definitions of GWI versus control veterans, no differences by levels of DU inhalation exposure, and no 236U associated with DU was detected. These findings show that even the highest likely levels of DU inhalation played no role in the development of GWI, leaving exposure to aerosolized organophosphate compounds (pesticides and sarin nerve agent) as the most likely cause(s) of GWI.


2021 ◽  
Vol 11 (7) ◽  
pp. 845
Author(s):  
Krishnan Radhakrishnan ◽  
Elizabeth R. Hauser ◽  
Renato Polimanti ◽  
Drew A. Helmer ◽  
Dawn Provenzale ◽  
...  

Background: Approximately 697,000 members of the U.S. Armed Forces were deployed to the Persian Gulf in support of the 1990–1991 Persian Gulf War (GW). Subsequently, many deployed and some non-deployed veterans developed a chronic multi-symptom illness, now named Gulf War Illness (GWI). This manuscript outlines the methods and rationale for studying the genomics of GWI within the Million Veteran Program (MVP), a VA-based national research program that has linked medical records, surveys, and genomic data, enabling genome-wide association studies (GWASs). Methods: MVP participants who served in the military during the GW era were contacted by mail and invited to participate in the GWI study. A structured health questionnaire, based on a previously tested instrument, was also included in the mailing. Data on deployment locations and exposures, symptoms associated with GWI, clinical diagnoses, personal habits, and health care utilization were collected. Self-reported data will be augmented with chart reviews and structured international classification of disease codes, to classify participants by GWI case status. We will develop a phenotyping algorithm, based on two commonly used case definitions, to determine GWI status, and then conduct a nested case-control GWAS. Genetic variants associated with GWI will be investigated, and gene–gene and gene–environment interactions studied. The genetic overlap of GWI with, and causative mechanisms linking this illness to, other health conditions and the effects of genomic regulatory mechanisms on GWI risk will also be explored. Conclusions: The proposed initial GWAS described in this report will investigate the genomic underpinnings of GWI with a large sample size and state-of-the-art genomic analyses and phenotyping. The data generated will provide a rich and expansive foundation on which to build additional analyses.


2020 ◽  
Vol 181 ◽  
pp. 108927 ◽  
Author(s):  
Geir Bjørklund ◽  
Lyudmila Pivina ◽  
Maryam Dadar ◽  
Yuliya Semenova ◽  
Md Mostafizur Rahman ◽  
...  

2006 ◽  
Author(s):  
Katherine N. Nguyen ◽  
Kendal C. Boyd

The Lancet ◽  
2005 ◽  
Vol 365 (9460) ◽  
pp. 635-638 ◽  
Author(s):  
M DEAHL
Keyword(s):  
Gulf War ◽  

2019 ◽  
Author(s):  
Zachary VanAernum ◽  
Florian Busch ◽  
Benjamin J. Jones ◽  
Mengxuan Jia ◽  
Zibo Chen ◽  
...  

It is important to assess the identity and purity of proteins and protein complexes during and after protein purification to ensure that samples are of sufficient quality for further biochemical and structural characterization, as well as for use in consumer products, chemical processes, and therapeutics. Native mass spectrometry (nMS) has become an important tool in protein analysis due to its ability to retain non-covalent interactions during measurements, making it possible to obtain protein structural information with high sensitivity and at high speed. Interferences from the presence of non-volatiles are typically alleviated by offline buffer exchange, which is timeconsuming and difficult to automate. We provide a protocol for rapid online buffer exchange (OBE) nMS to directly screen structural features of pre-purified proteins, protein complexes, or clarified cell lysates. Information obtained by OBE nMS can be used for fast (<5 min) quality control and can further guide protein expression and purification optimization.


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