The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide...The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.展开更多
Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now refe...Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.展开更多
Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic...Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic constipation,stomach pain,indigestion,diarrhea,and other conditions that severely impact the quality of life of GWI veterans.However,despite a high prevalence of gastrointestinal impairments among these veterans,most research attention has focused on neurological disturbances.This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI.Generally,these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI.Additionally,this perspective highlights the potential and challenges of in vitro bioengineering models,which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.展开更多
Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,a...Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].展开更多
Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a...Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a Food and Drug Administration(FDA)-approved cannabidiol(CBD),in improving brain function in a rat model of chronic GWI.Methods:Six months after exposure to low doses of GWI-related chemicals[pyridostigmine bromide,N,N-diethyl-meta-toluamide(DEET),and permethrin(PER)]along with moderate stress,rats with chronic GWI were administered either vehicle(VEH)or CBD(20 mg/kg,oral)for 16 weeks.Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory,object location memory,pattern separation,and sucrose preference.The effect of CBD on hyperalgesia was also examined.The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.Results:GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia,whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia.Additionally,CBD treatment alleviated hyperalgesia in GWI rats.Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription(JAK/STAT)signaling.Furthermore,there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis.In contrast,the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling,normalized concentrations of proinflammatory cytokines and oxidative stress markers,and improved neurogenesis.Notably,CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.Conclusions:The use of an FDA-approved CBD(Epidiolex®)has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI.Importantly,the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.展开更多
Background: Malondialdehyde(MDA) is a candidate general marker of oxidative stress(OS). We sought to assess the relation of MDA to Gulf War illness(GWI) and to a variety of exposures.Methods: This is an observational ...Background: Malondialdehyde(MDA) is a candidate general marker of oxidative stress(OS). We sought to assess the relation of MDA to Gulf War illness(GWI) and to a variety of exposures.Methods: This is an observational study involving subjects from Southern California recruited from October 2011 to May 2014. MDA was assessed in 81 participants(41 GWI-cases, 40 controls). General and Gulf-specific exposures were elicited. MDA case–control comparison was restricted to 40 matched pairs. The potential association between MDA and exposures was assessed using regression analyses. Gulf-specific exposures were incorporated into a case-specific model.Results: Plasma MDA was significantly lower in GWI-cases than controls. Composite pesticide and fuel-solvent exposures negatively predicted MDA in the total sample, as well as in the analyses that included either GWI-cases or controls only. Self-reported exposure to organophosphate(OP) nerve gas was a strong predictor for lower MDA level in veterans with GWI.Conclusions: Past pesticide exposures predicted lower MDA in both veterans with GWI and in healthy controls.展开更多
By its nature, Gulf war illness(GWI) is multi-symptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as ...By its nature, Gulf war illness(GWI) is multi-symptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation,pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war(GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies,which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.展开更多
Gulf War Illness(GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not limit...Gulf War Illness(GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not limited to)exposures to chemical agents and a foreign environment(e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants,may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure.展开更多
Gastrointestinal problems are common during wars, and they have exerted significant adverse effects on the health of service members involved in warfare. The spectrum of digestive diseases has varied during wars of di...Gastrointestinal problems are common during wars, and they have exerted significant adverse effects on the health of service members involved in warfare. The spectrum of digestive diseases has varied during wars of different eras. At the end of the 20 th century, new frontiers of military medical research emerged due to the occurrence of high-tech wars such as the Gulf War and the Kosovo War, in which ground combat was no longer the primary method of field operations. The risk to the military personnel who face trauma has been greatly reduced, but disease and non-battle injuries(DNBIs) such as neuropsychological disorders and digestive diseases seemed to be increased. Data revealed that gastrointestinal symptoms such as constipation, diarrhea, dyspepsia, and noncardiac chest pain are common among military personnel during modern wars. In addition, a large number of deployed soldiers and veterans who participated in recent wars presented with chronic gastrointestinal complaints, which fulfilled with the Rome III criteria for functional gastrointestinal disorders(FGIDs). It was also noted that many veterans who returned from the Gulf War suffered not only from chronic digestive symptoms but also from neuropsychological dysfunction; however, they also showed symptoms of other systems. Presently, this broad range of unexplained symptoms is known as "Gulf War syndrome". The mechanism that underlies Gulf War syndrome remains unclear, but many factors have been associated with this syndrome such as war trauma, stress, infections, immune dysfunction, radiological factors, anthrax vaccination and so on. Some have questioned if the diagnosis of FGIDs can be reached given the complexity of the military situation. As a result, further studies are needed to elucidate the pathogenesis of gastrointestinal disease among military personnel.展开更多
文摘The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.
基金suppor ted by the US Depar tment of Defense Congressionally Directed Medical Research Program (CDMRP)awards (http://cdmrp.army.mil/) W81XWH-16-1-0632 (Craddock PI),W81XWH-16-1-0552 (Craddock PI),W81XWH-18-1-0549 (Sullivan PI),W81XWH-13-2-0072 (Sullivan PI),and W81XWH-09-2-0071 (Klimas PI)a Veterans Affairs Merit Award (4987.69) to Dr.Nancy Klimas。
文摘Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
基金supported by the Congressionally Directed Medical Research Program Award through the Gulf War Illness Research Program (SAR, W81XWH-21±1-0477)funding from the Aviles-Johnson Doctoral Diversity Fellowship Awardthe National Defense Science and Engineering Graduate Fellowship Awards (CAC)
文摘Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic constipation,stomach pain,indigestion,diarrhea,and other conditions that severely impact the quality of life of GWI veterans.However,despite a high prevalence of gastrointestinal impairments among these veterans,most research attention has focused on neurological disturbances.This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI.Generally,these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI.Additionally,this perspective highlights the potential and challenges of in vitro bioengineering models,which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.
基金Department of Defense(W81XWH-17-1-0447 and W81XWH1910548 to AKS)Texas A&M University School of Medicine。
文摘Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].
基金supported by grants from Jazz Pharmaceuticals Inc.the Texas A&M University of School of Medicine to AKS
文摘Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a Food and Drug Administration(FDA)-approved cannabidiol(CBD),in improving brain function in a rat model of chronic GWI.Methods:Six months after exposure to low doses of GWI-related chemicals[pyridostigmine bromide,N,N-diethyl-meta-toluamide(DEET),and permethrin(PER)]along with moderate stress,rats with chronic GWI were administered either vehicle(VEH)or CBD(20 mg/kg,oral)for 16 weeks.Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory,object location memory,pattern separation,and sucrose preference.The effect of CBD on hyperalgesia was also examined.The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.Results:GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia,whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia.Additionally,CBD treatment alleviated hyperalgesia in GWI rats.Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription(JAK/STAT)signaling.Furthermore,there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis.In contrast,the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling,normalized concentrations of proinflammatory cytokines and oxidative stress markers,and improved neurogenesis.Notably,CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.Conclusions:The use of an FDA-approved CBD(Epidiolex®)has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI.Importantly,the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.
基金funded by the Depar tment of Defense Congressionally Directed Medical Research Program (GW093063)。
文摘Background: Malondialdehyde(MDA) is a candidate general marker of oxidative stress(OS). We sought to assess the relation of MDA to Gulf War illness(GWI) and to a variety of exposures.Methods: This is an observational study involving subjects from Southern California recruited from October 2011 to May 2014. MDA was assessed in 81 participants(41 GWI-cases, 40 controls). General and Gulf-specific exposures were elicited. MDA case–control comparison was restricted to 40 matched pairs. The potential association between MDA and exposures was assessed using regression analyses. Gulf-specific exposures were incorporated into a case-specific model.Results: Plasma MDA was significantly lower in GWI-cases than controls. Composite pesticide and fuel-solvent exposures negatively predicted MDA in the total sample, as well as in the analyses that included either GWI-cases or controls only. Self-reported exposure to organophosphate(OP) nerve gas was a strong predictor for lower MDA level in veterans with GWI.Conclusions: Past pesticide exposures predicted lower MDA in both veterans with GWI and in healthy controls.
基金the Department of Defense and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development。
文摘By its nature, Gulf war illness(GWI) is multi-symptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation,pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war(GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies,which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.
基金supported in part by the VA grant(5 I21 BX003760)to JMR.
文摘Gulf War Illness(GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not limited to)exposures to chemical agents and a foreign environment(e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants,may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure.
文摘Gastrointestinal problems are common during wars, and they have exerted significant adverse effects on the health of service members involved in warfare. The spectrum of digestive diseases has varied during wars of different eras. At the end of the 20 th century, new frontiers of military medical research emerged due to the occurrence of high-tech wars such as the Gulf War and the Kosovo War, in which ground combat was no longer the primary method of field operations. The risk to the military personnel who face trauma has been greatly reduced, but disease and non-battle injuries(DNBIs) such as neuropsychological disorders and digestive diseases seemed to be increased. Data revealed that gastrointestinal symptoms such as constipation, diarrhea, dyspepsia, and noncardiac chest pain are common among military personnel during modern wars. In addition, a large number of deployed soldiers and veterans who participated in recent wars presented with chronic gastrointestinal complaints, which fulfilled with the Rome III criteria for functional gastrointestinal disorders(FGIDs). It was also noted that many veterans who returned from the Gulf War suffered not only from chronic digestive symptoms but also from neuropsychological dysfunction; however, they also showed symptoms of other systems. Presently, this broad range of unexplained symptoms is known as "Gulf War syndrome". The mechanism that underlies Gulf War syndrome remains unclear, but many factors have been associated with this syndrome such as war trauma, stress, infections, immune dysfunction, radiological factors, anthrax vaccination and so on. Some have questioned if the diagnosis of FGIDs can be reached given the complexity of the military situation. As a result, further studies are needed to elucidate the pathogenesis of gastrointestinal disease among military personnel.
