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1.
Brain Behav Immun ; 65: 57-67, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28606462

RESUMO

Traumatic brain injury (TBI) is highly prevalent among a wide range of populations, including civilians, military personnel, and Veterans. TBI sequelae may be further exacerbated by symptoms associated with frequently occurring comorbid psychiatric conditions, including posttraumatic stress disorder (PTSD). This is particularly true among the population of military personnel from recent conflicts in Iraq and Afghanistan, with a history of mild TBI (mTBI) and PTSD. The need for efficacious treatments for TBI and comorbid PTSD is significant, and evidence-based interventions for these frequently co-occurring conditions are limited. Based on findings suggesting that inflammation may be an underlying mechanism of both conditions, anti-inflammatory/immunoregulatory agents, including probiotics, may represent a novel strategy to treat TBI and/or PTSD-related symptoms. The focus of this systematic review was to identify and evaluate existing research regarding prebiotic and probiotic interventions for the populations of individuals with a history of TBI and/or PTSD. Only 4 studies were identified (3 severe TBI, 1 PTSD, 0 co-occurring TBI and PTSD). Although findings suggested some promise, work in this area is nascent and results to date do not support some claims within the extensive coverage of probiotics in the popular press.


Assuntos
Síndrome Pós-Concussão/tratamento farmacológico , Probióticos/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Concussão Encefálica/tratamento farmacológico , Concussão Encefálica/microbiologia , Lesões Encefálicas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/microbiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Prebióticos/estatística & dados numéricos , Probióticos/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/microbiologia , Veteranos
2.
J Am Chem Soc ; 134(50): 20513-20, 2012 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-23153249

RESUMO

The ability to rationally modify enzymes to perform novel chemical transformations is essential for the rapid production of next-generation protein therapeutics. Here we describe the use of chemical principles to identify a naturally occurring acid-active peptidase, and the subsequent use of computational protein design tools to reengineer its specificity toward immunogenic elements found in gluten that are the proposed cause of celiac disease. The engineered enzyme exhibits a k(cat)/K(M) of 568 M(-1) s(-1), representing a 116-fold greater proteolytic activity for a model gluten tetrapeptide than the native template enzyme, as well as an over 800-fold switch in substrate specificity toward immunogenic portions of gluten peptides. The computationally engineered enzyme is resistant to proteolysis by digestive proteases and degrades over 95% of an immunogenic peptide implicated in celiac disease in under an hour. Thus, through identification of a natural enzyme with the pre-existing qualities relevant to an ultimate goal and redefinition of its substrate specificity using computational modeling, we were able to generate an enzyme with potential as a therapeutic for celiac disease.


Assuntos
Gliadina/química , Peptídeo Hidrolases/química , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular
3.
Artigo em Inglês | MEDLINE | ID: mdl-30510919

RESUMO

Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.


Assuntos
Disbiose , Microbiota , Militares/psicologia , Determinantes Sociais da Saúde , Saúde dos Veteranos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Estados Unidos , United States Department of Veterans Affairs , Veteranos , Adulto Jovem
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