-
Shock (Augusta, Ga.) Feb 2022Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies...
Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. In particular, intoxication at the time of burn injury leads to compromised intestinal T cell responses, which can diminish intestinal immunity and promote bacterial translocation, allowing for increased secondary infections in the injured host and associated sequelae, such as multiple organ failure and sepsis. Regulatory T cells (Treg) have been identified as important mediators of suppressing effector T cell function. Therefore, the goal of this study was to assess the effects of ethanol intoxication and burn injury on Treg populations in small intestinal immune organs. We also evaluated the suppressive capability of Tregs isolated from injured animals. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a ∼12.5% total body surface area scald burn. One day after injury, we identified a significant increase in Tregs number in small intestine Peyer's patches (∼×1.5) and lamina propria (∼×2). Tregs-producing cytokine IL-10 were also increased in both tissues. Finally, Tregs isolated from ethanol and burn-injured mice were able to suppress proliferation of effector T cells to a greater degree than sham vehicle Tregs. This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol + burn Tregs compared with sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues 1 day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn-injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.
Topics: Alcoholic Intoxication; Animals; Burns; Intestine, Small; Male; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory
PubMed: 34482318
DOI: 10.1097/SHK.0000000000001853 -
Journal of Controlled Release :... Nov 2020Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid... (Review)
Review
Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.
Topics: Drug Delivery Systems; Drug Liberation; Humans; Inflammation; Inflammatory Bowel Diseases; Tissue Distribution
PubMed: 32911014
DOI: 10.1016/j.jconrel.2020.09.008 -
Burns & Trauma 2023Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear pathogenesis, the current therapeutic strategy for IBD is focused on symptoms alleviation. Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis. Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms, including modulating macrophage function. Macrophages are the gatekeepers of intestinal immune homeostasis, especially involved in regulating inflammation remission and tissue repair. Interestingly, many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function, suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation. Here, we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance, inflammation remission and tissue repair regulation in IBD, and discuss how this knowledge can be used as a strategy for IBD treatment.
PubMed: 37152076
DOI: 10.1093/burnst/tkad004 -
The Journal of Allergy and Clinical... Dec 2023Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2),... (Observational Study)
Observational Study
BACKGROUND
Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments.
OBJECTIVE
We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD.
METHODS
We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium.
RESULTS
We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD.
CONCLUSION
Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.
Topics: Humans; Granulomatous Disease, Chronic; Gastrointestinal Microbiome; NADPH Oxidases; Cross-Sectional Studies; Inflammatory Bowel Diseases
PubMed: 37659505
DOI: 10.1016/j.jaci.2023.07.022 -
Journal of Leukocyte Biology Nov 2021The gastrointestinal (GI) tract is a highly dynamic structure essential for digestion, nutrient absorption, and providing an interface to prevent gut bacterial... (Review)
Review
The gastrointestinal (GI) tract is a highly dynamic structure essential for digestion, nutrient absorption, and providing an interface to prevent gut bacterial translocation. In order to maintain the barrier function, the gut utilizes many defense mechanisms including proliferation, apoptosis, and apical junctional complexes. Disruption of any of these parameters due to injury or disease could negatively impact the intestinal barrier function and homeostasis resulting in increased intestine inflammation, permeability, bacterial dysbiosis, and tissue damage. MicroRNAs are small noncoding RNA sequences that are master regulators of normal cellular homeostasis. These regulatory molecules affect cellular signaling pathways and potentially serve as candidates for providing a mechanism of impaired gut barrier integrity following GI-related pathologic conditions, ethanol exposure, or trauma such as burn injury. MicroRNAs influence cellular apoptosis, proliferation, apical junction complex expression, inflammation, and the microbiome. Due to their widespread functional affiliations, altered expression of microRNAs are associated with many pathologic conditions. This review explores the role of microRNAs in regulation of intestinal barrier integrity. The studies reviewed demonstrate that microRNAs largely impact intestine barrier function and provide insight behind the observed adverse effects following ethanol and burn injury. Furthermore, these studies suggest that microRNAs are excellent candidates for therapeutic intervention or for biomarkers to manage gut barrier integrity following trauma such as burn injury and other GI-related pathologic conditions.
Topics: Animals; Humans; Intestinal Mucosa; Intestines; Permeability; RNA, Messenger; Tight Junctions
PubMed: 33577717
DOI: 10.1002/JLB.3RU0120-090RR -
Frontiers in Cellular and Infection... 2022Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut... (Review)
Review
Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut microbiome, the largest microbial reservoir in the human body, plays a significant role in this pathogenic process. Intestinal dysbiosis and disruption of the intestinal mucosal barrier are common after severe burn, leading to bacterial translocation to the bloodstream and other organs of the body, which is associated with many subsequent severe complications. The progression of some intestinal diseases can be improved by modulating the composition of gut microbiota and the levels of its metabolites, which also provides a promising direction for post-burn treatment. In this article, we summarised the studies describing changes in the gut microbiome after severe burn, as well as changes in the function of the intestinal mucosal barrier. Additionally, we presented the potential and challenges of microbial therapy, which may provide microbial therapy strategies for severe burn.
Topics: Humans; Gastrointestinal Microbiome; Bacterial Translocation; Intestinal Mucosa; Sepsis
PubMed: 36467727
DOI: 10.3389/fcimb.2022.974259 -
BMJ Open Gastroenterology Apr 2022Inflammatory bowel disease clinical nurse specialists (IBD-CNSs) face increasing pressures due to rising clinical and patient demands, advanced complexity of work role,... (Review)
Review
Scoping review with textual narrative synthesis of the literature reporting stress and burn-out in specialist nurses: making the case for inflammatory bowel disease nurse specialists.
OBJECTIVE
Inflammatory bowel disease clinical nurse specialists (IBD-CNSs) face increasing pressures due to rising clinical and patient demands, advanced complexity of work role, and minimal specialist management training and support. Stress and burn-out could undermine the stability of this workforce, disrupting clinical provision. We reviewed the literature on stress and burn-out to demonstrate the lack of evidence pertinent to IBD-CNSs and make the case for further research.
DESIGN
Following Levac 's scoping review framework, relevant databases were searched for publications reporting work-related stress and burn-out among specialist nurses. Following screening and consensus on selection of the final articles for review, all authors contributed to data charting. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension guided reporting of the review.
RESULTS
Of 194 retrieved articles, eight were eligible for review. None focused on IBD-CNSs, were qualitative, or UK-based. Three core themes were identified: Rates of Burn-out, Mitigating and Alleviating Factors, and Preventing and Resolving Burn-out. Risk of burn-out is greatest in novice and mid-career CNSs. Age and duration in role appear protective. Personal achievement is also protective and can mitigate earlier episodes of burn-out; opportunities for career progression are limited. Promoting personal well-being is beneficial. Senior managers have poor understanding of the role and provide inadequate support. Commitment to patients remains high.
CONCLUSION
Burn-out arises in CNSs across clinical specialisms in the international literature and has a significant negative effect on the workforce. Further research is needed to address the dearth of evidence on burn-out in IBD-CNSs in the UK.
Topics: Burnout, Professional; Humans; Inflammatory Bowel Diseases; Nurse Clinicians; Nurse Specialists
PubMed: 35428670
DOI: 10.1136/bmjgast-2021-000852 -
Surgical Case Reports Sep 2021Severe electrical burns are a rare cause of admission to major burn centers. Incidence of electrical injury causing full-thickness injury to viscera is an increasingly...
BACKGROUND
Severe electrical burns are a rare cause of admission to major burn centers. Incidence of electrical injury causing full-thickness injury to viscera is an increasingly scarce, but severe presentation requiring rapid intervention. We report one of few cases of a patient with full-thickness electrical injury to the abdominal wall, bowel, and bladder.
CASE REPORT
The patient, a 22-year-old male, was transferred to our institution from his local hospital after sustaining a suspected electrical burn. On arrival the patient was noted to have severe burn injuries to the lower abdominal wall with evisceration of multiple loops of burned small bowel as well as burns to the groin, left upper, and bilateral lower extremities. In the trauma bay, primary and secondary surveys were completed, and the patient was taken for CT imaging and then emergently to the operating room. On exploration, the patient had massive full-thickness burns to the lower abdominal wall, five full-thickness burns to small bowel, and intraperitoneal bladder rupture secondary to full-thickness burn. The patient underwent damage-control laparotomy including enterectomies, debridement of bladder coagulative necrosis, and layered closure of bladder injury followed by temporary abdominal closure with vacuum dressing. The patient also underwent right leg escharotomy and partial right foot fasciotomies. The patient was subsequently transferred to the nearest burn center for continued resuscitation and comprehensive burn care.
CONCLUSION
Severe electrical burns can be associated with devastating visceral injuries in rare cases. Though uncommon, these injuries are associated with very high mortality rates. The authors assert that rapid evaluation and initial stabilization following ATLS guidelines, damage-control laparotomy, and goal-directed resuscitation in concert with transfer to a major burn center are essential in effecting a successful outcome in these challenging cases.
PubMed: 34585274
DOI: 10.1186/s40792-021-01302-8 -
World Journal of Clinical Cases Aug 2023It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial...
BACKGROUND
It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial symptom. The severity of coronavirus disease 2019 (COVID-19) is often reflected in the prevalence of gastrointestinal symptoms. COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction. There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.
AIM
To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction, including its manifestations, potential mechanisms, diagnosis, differential diagnosis, impact on quality of life, prognosis, and management and prevention strategies.
METHODS
We conducted a thorough systematic search across various databases and performed an extensive literature review. Our review encompassed 113 studies published in English from January 2000 to April 18, 2023.
RESULTS
According to most of the literature, gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis. Numerous factors can influence gastrointestinal autonomic nervous functions. Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues, and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways. These symptoms include anorexia, dysgeusia, heartburn, belching, chest pain, regurgitation, vomiting, epigastric burn, diarrhea, abdominal pain, bloating, irregular bowel movements, and constipation. Diarrhea is the most prevalent symptom, followed by anorexia, nausea, vomiting, and abdominal pain. Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms, COVID-19-induced autonomic effects significantly impact the patient's condition, general health, prognosis, and quality of life. Early diagnosis and proper recognition are crucial for improving outcomes. It is important to consider the differential diagnosis, as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction. Treating this dysfunction can be a challenging task.
CONCLUSION
To ensure the best possible outcomes for COVID-19 patients, it is essential to take a multidisciplinary approach involving providing supportive care, treating the underlying infection, managing dysfunction, monitoring for complications, and offering nutritional support. Close monitoring of the patient's condition is crucial, and prompt intervention should be taken if necessary. Furthermore, conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.
PubMed: 37621592
DOI: 10.12998/wjcc.v11.i22.5252 -
Frontiers in Neuroscience 2022Circadian rhythms are cyclic patterns of physiological, behavioural and molecular events that occur over a 24-h period. They are controlled by the suprachiasmatic... (Review)
Review
Circadian rhythms are cyclic patterns of physiological, behavioural and molecular events that occur over a 24-h period. They are controlled by the suprachiasmatic nucleus (SCN), the brain's master pacemaker which governs peripheral clocks and melatonin release. While circadian systems are endogenous, there are external factors that synchronise the SCN to the ambient environment including light/dark cycles, fasting/fed state, temperature and physical activity. Circadian rhythms also provide internal temporal organisation which ensures that any internal changes that take place are centrally coordinated. Melatonin synchronises peripheral clocks to the external time and circadian rhythms are regulated by gene expression to control physiological function. Synchronisation of the circadian system with the external environment is vital for the health and survival of an organism and as circadian rhythms play a pivotal role in regulating GI physiology, disruption may lead to gastrointestinal (GI) dysfunction. Disorders of gut-brain interactions (DGBIs), also known as functional gastrointestinal disorders (FGIDs), are a group of diseases where patients experience reoccurring gastrointestinal symptoms which cannot be explained by obvious structural abnormalities and include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Food timing impacts on the production of melatonin and given the correlation between food intake and symptom onset reported by patients with DGBIs, chronodisruption may be a feature of these conditions. Recent advances in immunology implicate circadian rhythms in the regulation of immune responses, and DGBI patients report fatigue and disordered sleep, suggesting circadian disruption. Further, melatonin treatment has been demonstrated to improve symptom burden in IBS patients, however, the mechanisms underlying this efficacy are unclear. Given the influence of circadian rhythms on gastrointestinal physiology and the immune system, modulation of these rhythms may be a potential therapeutic option for reducing symptom burden in these patients.
PubMed: 35356051
DOI: 10.3389/fnins.2022.825246