RESUMO
As primary flavonoids extracted from citrus fruits, hesperidin has been attracting attention widely for its capacity to act as antioxidants that are able to scavenge free radicals and reactive oxygen species (ROS). Many factors have made oxidative stress a risk factor for the occurrence of intestinal barrier injury, which is a serious health threat to human beings. However, little data are available regarding the underlying mechanism of hesperidin alleviating intestinal injury under oxidative stress. Recently, endoplasmic reticulum (ER) mitochondria contact sites (ERMCSs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and Ca2+ transport. In our experiment, 24 piglets were randomly divided into 4 groups. Piglets in the diquat group and hesperidin + diquat group received an intraperitoneal injection of diquat (10 mg/kg), while piglets in the hesperidin group and hesperidin + diquat group received hesperidin (300 mg/kg) with feed. The results indicated that hesperidin alleviated growth restriction and intestinal barrier injury in piglets compared with the diquat group. Hesperidin ameliorated oxidative stress and restored antioxidant capacity under diquat exposure. The mitochondrial dysfunction was markedly alleviated via hesperidin versus diquat group. Meanwhile, hesperidin alleviated ER stress and downregulated the PERK pathway. Furthermore, hesperidin prevented the disorder of ERMCSs by downregulating the level of ERMCS proteins, decreasing the percentage of mitochondria with ERMCSs/total mitochondria and the ratio of ERMCSs length/mitochondrial perimeter. These results suggested hesperidin could alleviate ERMCS disorder and prevent mitochondrial dysfunction, which subsequently decreased ROS production and alleviated intestinal barrier injury of piglets under oxidative stress.
Assuntos
Retículo Endoplasmático , Hesperidina , Mucosa Intestinal , Mitocôndrias , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Estresse Oxidativo/efeitos dos fármacos , Hesperidina/farmacologia , Suínos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/lesões , Masculino , Humanos , Antioxidantes/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacosRESUMO
OBJECTIVES: Intestinal ischemia-reperfusion (I/R) injury is a multifactorial and complex clinical pathophysiological process. Current research indicates that the pathogenesis of intestinal I/R injury involves various mechanisms, including ferroptosis. Methane saline (MS) has been demonstrated to primarily exert anti-inflammatory and antioxidant effects in I/R injury. In this study, we mainly investigated the effect of MS on ferroptosis in intestinal I/R injury and determined its potential mechanism. METHODS: In vivo and in vitro intestinal I/R injury models were established to validate the relationship between ferroptosis and intestinal I/R injury. MS treatment was applied to assess its impact on intestinal epithelial cell damage, intestinal barrier disruption, and ferroptosis. RESULTS: MS treatment led to a reduction in I/R-induced intestinal epithelial cell damage and intestinal barrier disruption. Moreover, similar to treatment with ferroptosis inhibitors, MS treatment reduced ferroptosis in I/R, as indicated by a decrease in the levels of intracellular pro-ferroptosis factors, an increase in the levels of anti-ferroptosis factors, and alleviation of mitochondrial damage. Additionally, the expression of Nrf2/HO-1 was significantly increased after MS treatment. However, the intestinal protective and ferroptosis inhibitory effects of MS were diminished after the use of M385 to inhibit Nrf2 in mice or si-Nrf2 in Caco-2 cells. DISCUSSION: We proved that intestinal I/R injury was mitigated by MS and that the underlying mechanism involved modulating the Nrf2/HO-1 signaling pathway to decrease ferroptosis. MS could be a promising treatment for intestinal I/R injury.
Assuntos
Ferroptose , Heme Oxigenase-1 , Metano , Fator 2 Relacionado a NF-E2 , Traumatismo por Reperfusão , Transdução de Sinais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Camundongos , Heme Oxigenase-1/metabolismo , Metano/farmacologia , Masculino , Humanos , Solução Salina/farmacologia , Intestinos/efeitos dos fármacos , Intestinos/lesões , Camundongos Endogâmicos C57BL , Proteínas de MembranaRESUMO
Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.
Assuntos
Sepse , Humanos , Sepse/complicações , Sepse/etiologia , Sepse/fisiopatologia , Hepatopatias/etiologia , Intestinos/lesões , Animais , Microbioma GastrointestinalRESUMO
Foreign body ingestion of sharp objects can be a striking feature of psychological dysfunction with high morbidity and mortality. While the phenomenon has been reported on, primarily from a psychiatric perspective, this report will present the effects of this behavior on the intestinal system from a pathology perspective. The report is of a 43-year-old female with a past medical history of foreign object ingestion, borderline personality disorder, depression, anxiety, and prior suicidality who passed away due to bowel obstruction. Review of her history revealed an eighteen-year history of repeated foreign body ingestion with multiple surgical interventions. A particularly remarkable aspect revealed through the surgical history is the nature of the complications. They begin in 2008 with bowel perforation due to a blunt object and continue to present with perforation in the early years but show a gradual change to adhesions and obstruction as the primary concern. Her final presentation to the hospital and cause of death was due to obstruction, not perforation, even though the foreign bodies were six knives. While this case is not the only known report of foreign body ingestion, the extensive timeline and frequency allow for an examination of the gradual progression of fibrosis and adhesions within the intestines and abdominal wall, which led to the obstruction and death despite being a protective factor against further perforation.This case was presented at the annual Association of Clinical Scientists meeting (April 2-4, Jacksonville, FL).
Assuntos
Fibrose , Corpos Estranhos , Intestinos , Humanos , Feminino , Adulto , Corpos Estranhos/complicações , Intestinos/patologia , Intestinos/lesões , Obstrução Intestinal/etiologia , Obstrução Intestinal/patologia , Evolução Fatal , Perfuração Intestinal/etiologia , Perfuração Intestinal/patologia , Perfuração Intestinal/cirurgiaAssuntos
Inteligência Artificial , Recém-Nascido Prematuro , Humanos , Recém-Nascido , Intestinos/lesõesRESUMO
ABSTRACT: Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx-, cell junction-, and PI3K/Akt/NF-κB signaling pathway-related proteins was analyzed by western blot. Results : MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.
Assuntos
Intestinos , MicroRNAs , Solução de Ringer , Choque Hemorrágico , Animais , Masculino , Ratos , Glicocálix/efeitos dos fármacos , Glicocálix/metabolismo , Glicocálix/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Intestinos/patologia , Intestinos/efeitos dos fármacos , Intestinos/lesões , Soluções Isotônicas/farmacologia , Soluções Isotônicas/uso terapêutico , MicroRNAs/metabolismo , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Ressuscitação , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Choque Hemorrágico/complicações , Transdução de Sinais/efeitos dos fármacos , Bicarbonato de Sódio/uso terapêutico , Bicarbonato de Sódio/farmacologia , Solução de Ringer/farmacologia , Solução de Ringer/uso terapêuticoRESUMO
PURPOSE: Blunt bowel and/or mesenteric injury requiring surgery presents a diagnostic challenge. Although computed tomography (CT) imaging is standard following blunt trauma, findings can be nonspecific. Most studies have focused on the diagnostic value of CT findings in identifying significant bowel and/or mesenteric injury (sBMI). Some studies have described scoring systems to assist with diagnosis. Little attention, has been given to radiologist interpretation of CT scans. This study compared the discriminative ability of scoring systems (BIPS and RAPTOR) with radiologist interpretation in identifying sBMI. METHODS: We conducted a retrospective chart review of trauma patients with suspected sBMI. CT images were reviewed in a blinded fashion to calculate BIPS and RAPTOR scores. Sensitivity and specificity were compared between BIPS, RAPTOR, and the admission CT report with respect to identifying sBMI. RESULTS: One hundred sixty-two patients were identified, 72 (44%) underwent laparotomy and 43 (26.5%) had sBMI. Sensitivity and specificity were: BIPS 49% and 87%, AUC 0.75 (0.67-0.81), P < 0.001; RAPTOR 46% and 82%, AUC 0.72 (0.64-0.79), P < 0.001; radiologist impression 81% and 71%, AUC 0.82(0.75-0.87), P < 0.001. The discriminative ability of the radiologist impression was higher than RAPTOR (P = 0.04) but not BIPS (P = 0.13). There was not a difference between RAPTOR vs. BIPS (P = 0.55). CONCLUSION: Radiologist interpretation of the admission CT scan was discriminative of sBMI. Although surgical vigilance, including evaluation of the CT images and patient, remains fundamental to early diagnosis, the radiologist's impression of the CT scan can be used in clinical practice to simplify the approach to patients with abdominal trauma.
Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Humanos , Estudos Retrospectivos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/lesões , Intestinos/lesões , Tomografia Computadorizada por Raios X/métodos , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/cirurgiaRESUMO
ABSTRACT: Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using hematoxylin and eosin staining. Oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established to mimic ischemic injury in vitro . Transient transfection was used to overexpress or knock down genes. Cell death or apoptosis was assessed by propidium iodide staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and flow cytometry. The expression of proteins was detected by western blot. The histopathology observed by hematoxylin and eosin staining suggested that the IIRI animal model was successfully established. Our findings revealed that IIRI resulted in increased Bax and decreased Bcl-2 levels. In vitro experiments showed that overexpression of Parkin decreased OGD/R injury and suppressed elevation of Bax/Bcl-2. PRMT6 regulated the methylation level of FoxO3a. Moreover, FoxO3a directly binds to Parkin, and FoxO3a overexpression reduced OGD/R-induced cell death and regulation of Parkin. Overexpression of PRMT6 can attenuate the downregulation of Parkin and elevation of Bax/Bcl-2 caused by OGD/R. Knockdown of PRMT6 promoted apoptosis in intestinal epithelial cells of OGD/R group, while PRMT6 overexpression exhibited the opposite effect. Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.
Assuntos
Apoptose , Proteína Forkhead Box O3 , Intestinos , Proteína-Arginina N-Metiltransferases , Traumatismo por Reperfusão , Animais , Camundongos , Apoptose/genética , Proteína Forkhead Box O3/metabolismo , Intestinos/patologia , Intestinos/lesões , Intestinos/irrigação sanguínea , Camundongos Endogâmicos C57BL , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Regulação para CimaRESUMO
OBJETIVO: Analisar os fatores de risco para complicações de lesão periestomal em estomas de eliminação. MÉTODO: Uma revisão sistemática e um protocolo de meta-síntese serão conduzidos de acordo com o checklist Principais Itens para Relatar Revisões Sistemáticas e Metanálises (PRISMA) e as diretrizes e recomendações metodológicas do Joanna Briggs Institute (JBI). Dois pesquisadores independentes realizarão buscas nas seguintes bases de dados: Web of Science, Scopus, Embase, PubMed via CAPES e LILACS. Os estudos elegíveis incluirão estudos observacionais, estudos experimentais e estudos quase-experimentais publicados em inglês, espanhol e português, com foco em fatores de risco para complicações da pele periestomal em estomas de eliminação. Será utilizado o software Rayyan Intelligent para auxiliar no processo de seleção dos estudos. O risco de viés será apresentado usando gráficos de barras ponderadas e gráficos de semáforos para exibir os resultados para cada domínio avaliado em cada estudo incluído. A metassíntese será realizada em software de análise qualitativa, empregando análise de similaridade textual.
OBJECTIVE: To analyze risk factors for peristomal skin complications in elimination stomas. METHOD: A systematic review and meta-synthesis protocol will be conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methodological guidelines and recommendations of the Joanna Briggs Institute (JBI). Two independent researchers will search the following databases: Web of Science, Scopus, Embase, PubMed via CAPES, and LILACS. Eligible studies will include observational, experimental, and quasi-experimental studies published in English, Spanish, and Portuguese, focusing on risk factors for peristomal skin complications in elimination stomas. A software will be used to aid in the study selection process. The risk of bias will be presented using weighted bar graphs and traffic light plots to display the results for each assessed domain in each included study. The meta-synthesis will be conducted using qualitative analysis software, employing textual similarity analysis.
Assuntos
Sistema Urinário/lesões , Ferimentos e Lesões/complicações , Estomia , Fatores de Risco , Intestinos/lesões , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Avoiding missed diagnosis and therapeutic delay for significant blunt bowel and mesenteric injuries (sBBMIs) after trauma is still challenging despite the widespread use of computed tomography (CT). Several scoring tools aiming at reducing this risk have been published. The purpose of the present work was to assess the incidence of delayed (>24 hours) diagnosis for sBBMI patients and to compare the predictive performance of three previously published scores using clinical, radiological, and laboratory findings: the Bowel Injury Prediction Score (BIPS) and the scores developed by Raharimanantsoa Score (RS) and by Faget Score (FS). METHODS: A population-based retrospective observational cohort study was conducted; it included adult trauma patients after road traffic crashes admitted to Lausanne University Hospital, Switzerland, between 2008 and 2019 (n = 1,258) with reliable information about sBBMI status (n = 1,164) and for whom all items for score calculation were available (n = 917). The three scores were retrospectively applied on all patients to assess their predictive performance. RESULTS: The incidence of sBBMI after road traffic crash was 3.3% (38 of 1,164), and in 18% (7 of 38), there was a diagnostic and treatment delay of more than 24 hours. The diagnostic performances of the FS, the RS, and the BIPS to predict sBBMI, expressed as the area under the receiver operating characteristic curve, were 95.3% (95% confidence interval [CI], 92.7-97.9%), 89.2% (95% CI, 83.2-95.3%), and 87.6% (95% CI, 81.8-93.3%) respectively. CONCLUSION: The present study confirms that diagnostic delays for sBBMI still occur despite the widespread use of abdominal CT. When CT findings during the initial assessment are negative or equivocal for sBBMI, using a score may be helpful to select patients for early diagnostic laparoscopy. The FS had the best individual diagnostic performance. However, the BIPS or the RS, relying on clinical and laboratory variables, may be helpful to select patients for early diagnostic laparoscopy when there are unspecific CT signs of bowel or mesenteric injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.
Assuntos
Diagnóstico Tardio , Mesentério , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes , Humanos , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Adulto , Diagnóstico Tardio/estatística & dados numéricos , Pessoa de Meia-Idade , Mesentério/lesões , Mesentério/diagnóstico por imagem , Suíça/epidemiologia , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/diagnóstico por imagem , Intestinos/lesões , Intestinos/diagnóstico por imagem , Acidentes de Trânsito/estatística & dados numéricos , Escala de Gravidade do Ferimento , Valor Preditivo dos Testes , Idoso , IncidênciaAssuntos
Traumatismos Abdominais , Imunidade , Ferimentos não Penetrantes , Humanos , Intestinos/lesõesRESUMO
BACKGROUND: Sepsis is a dysregulated host response to infection syndrome leading to life-threatening organ dysfunction. Sepsis-induced intestinal dysfunction is a key element in the progression to multisystem organ failure. The stimulator of interferon genes is an intracellular protein implicated in intestinal injury in sepsis. H151, a small molecule inhibitor of stimulator of interferon genes, has not yet been studied as a potential therapeutic in sepsis. We hypothesize that H151 therapeutically reduces sepsis-induced acute intestinal injury. METHODS: Male mice underwent cecal ligation and puncture and were treated with intraperitoneal H151 (10 mg/kg body weight) or vehicle. Intestines and serum were collected for analysis 20 hours after cecal ligation and puncture. Oral gavage of mice with FITC-dextran was performed 15 hours after cecal ligation and puncture. Five hours after gavage, serum was collected, and intestinal permeability was assessed. Mice were monitored for 10 days after cecal ligation and puncture to assess survival. RESULTS: Zonula occludens 1 tight junctional protein expression was reduced after cecal ligation and puncture and recovered with H151 treatment. This was associated with a 62.3% reduction in intestinal permeability as assessed by fluorimetry. After cecal ligation and puncture, treatment with H151 was associated with a 58.7% reduction in intestinal histopathologic injury (P < .05) and a 56.6% reduction in intestinal apoptosis (P < .05). Intestinal myeloperoxidase activity was decreased by 70.8% after H151 treatment (P < .05). Finally, H151 improved 10-day survival from 33% to 80% after cecal ligation and puncture (P = .011). CONCLUSION: H151, a novel stimulator of interferon genes inhibitor, reduces intestinal injury, inflammation, and permeability when administered as a treatment for cecal ligation and puncture-induced sepsis. Thus, targeting stimulator of interferon genes shows promise as a therapeutic strategy to ameliorate sepsis-induced acute intestinal injury.
Assuntos
Traumatismos Abdominais , Enteropatias , Sepse , Camundongos , Masculino , Animais , Intestinos/lesões , Inflamação/patologia , Fatores de Transcrição , Ligadura , Interferons/uso terapêutico , Modelos Animais de Doenças , Ceco/cirurgia , Ceco/lesões , Ceco/patologiaRESUMO
We present the case of a man in his 30s who was crushed between two vehicles sustaining blunt trauma to his lower limbs and torso. The patient was in shock on arrival to the emergency department, and immediate resuscitation was given with massive transfusion protocol activation. Once the patient's haemodynamic status was stabilised, a CT scan revealed a complete colon transection. The patient was taken to the operating theatre where a midline laparotomy was performed, and the transected descending colon was managed with a segmental resection and handsewn anastomosis. The patient followed an unremarkable postoperative course, with bowels opening on day 8 postoperatively. Colon injuries are rare following blunt abdominal trauma, and a delay in diagnosis may lead to increased morbidity and mortality. As such, a low threshold for surgical intervention is recommended.
Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Masculino , Humanos , Colo Descendente , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/cirurgia , Ferimentos não Penetrantes/diagnóstico , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Tomografia Computadorizada por Raios X , Intestinos/lesõesRESUMO
BACKGROUND: Primary aim was to assess the relative risk (RR) of anastomotic leak (AL) in intestinal bucket-handle (BH) compared to non-BH injury. METHODS: Multi-center study comparing AL in BH from blunt trauma 2010-2021 compared to non-BH intestinal injuries. RR was calculated for small bowel and colonic injury using R. RESULTS: AL occurred in 20/385 (5.2%) of BH vs. 4/225 (1.8%) of non-BH small intestine injury. AL was diagnosed 11.6 ± 5.6 days from index operation in small intestine BH and 9.7 ± 4.3 days in colonic BH. Adjusted RR for AL was 2.32 [0.77-6.95] for small intestinal and 4.83 [1.47-15.89] for colonic injuries. AL increased infections, ventilator days, ICU & total length of stay, reoperation, and readmission rates, although mortality was unchanged. CONCLUSION: BH carries a significantly higher risk of AL, particularly in the colon, than other blunt intestinal injuries.
Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos Retrospectivos , Colo/cirurgia , Colo/lesões , Intestinos/lesões , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/cirurgia , Anastomose CirúrgicaRESUMO
The increasing applications of ionizing radiation in society raise the risk of radiation-induced intestinal and whole-body injury. Astaxanthin is a powerful antioxidant to reduce the reactive oxygen generated from radiation and the subsequent damage. However, the oral administration of astaxanthin remains challenging owing to its low solubility and poor bioavailability. Herein, we facilely construct an orally used microalgae-nano integrated system (SP@ASXnano) against radiation-induced intestinal and whole-body injury, combining natural microalgae Spirulina platensis (SP) with astaxanthin nanoparticles (ASXnano). SP and ASXnano show complementation in drug delivery to improve distribution in the intestine and blood. SP displays limited gastric drug loss, prolonged intestinal retention, constant ASXnano release, and progressive degradation. ASXnano improves drug solubility, gastric stability, cell uptake, and intestinal absorption. SP and ASXnano have synergy in many aspects such as anti-inflammation, microbiota protection, and fecal short-chain fatty acid up-regulation. In addition, the system is ensured with biosafety for long-term administration. The system organically combines the properties of microalgae and nanoparticles, which was expected to expand the medical application of SP as a versatile drug delivery platform.
Assuntos
Microalgas , Nanopartículas , Lesões por Radiação , Administração Oral , Microalgas/química , Lesões por Radiação/tratamento farmacológico , Nanopartículas/química , Intestinos/lesões , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , CamundongosRESUMO
This article describes the case of a woman who unknowingly swallowed several fishbones, one of which perforated the intestinal wall and subsequently formed an intra-abdominal abscess due to the foreign body reaction.
Assuntos
Abscesso Abdominal , Reação a Corpo Estranho , Feminino , Humanos , Abscesso Abdominal/etiologia , Deglutição , Peixes , Osso e Ossos , Intestinos/lesõesRESUMO
BACKGROUND: The impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. METHODS: We measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the "high" and "low" IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. RESULTS: Several markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the "high" IFABP group, and all six patients who had been transferred to ward were in the "low" group. Of patients still treated in the ICU, the "high" group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). CONCLUSION: Cardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.
Assuntos
Intestinos , Parada Cardíaca Extra-Hospitalar , Humanos , Intestinos/lesões , Estudos Prospectivos , Insuficiência de Múltiplos Órgãos/etiologia , Biomarcadores , Escores de Disfunção Orgânica , Parada Cardíaca Extra-Hospitalar/complicações , Lactatos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: The inflammatory response induced by intestinal ischaemiaâreperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.
Assuntos
Cistationina gama-Liase , Intestinos , Sistema de Sinalização das MAP Quinases , Macrófagos , Animais , Cistationina gama-Liase/metabolismo , Macrófagos/metabolismo , Fagocitose , Transdução de Sinais , Humanos , Camundongos , Intestinos/lesões , Intestinos/fisiologiaRESUMO
OBJECTIVES: To develop a CT-based algorithm and evaluate its performance for the diagnosis of blunt bowel and/or mesenteric injury (BBMI) in patients with blunt abdominal trauma. METHODS: This retrospective study included a training cohort of 79 patients (29 with BBMI and 50 patients with blunt abdominal trauma without BBMI) and a validation cohort of 37 patients (13 patients with BBMI and 24 patients with blunt abdominal trauma without BBMI). CT examinations were blindly analyzed by two independent radiologists. For each CT sign, the kappa value, sensitivity, specificity, and accuracy were calculated. A diagnostic algorithm was built using a recursive partitioning model on the training cohort, and its performances were assessed on the validation cohort. RESULTS: CT signs with kappa value > 0.6 were extraluminal gas, hemoperitoneum, no or moderate bowel wall enhancement, and solid organ injury. CT signs yielding best accuracies in the training cohort were extraluminal gas (98%; 95% CI: 91-100), bowel wall defect (97%; 95% CI: 91-100), irregularity of mesenteric vessels (97%; 95% CI: 90-99), and mesenteric vessel extravasation (97%; 95% CI: 90-99). Using a recursive partitioning model, a decision tree algorithm including extraluminal gas and no/moderate bowel wall enhancement was built, achieving 86% sensitivity (95% CI: 74-99) and 96% specificity (95% CI: 91-100) in the training cohort and 92% sensitivity (95% CI: 78-97) and 88% specificity (95% CI: 74-100) in the validation cohort for the diagnosis of BBMI. CONCLUSIONS: An effective diagnostic algorithm was built to identify BBMI in patients with blunt abdominal trauma using only extraluminal gas and no/moderate bowel wall enhancement on CT examination. KEY POINTS: ⢠A CT diagnostic algorithm that included extraluminal gas and no/moderate bowel wall enhancement was built for the diagnosis of surgical blunt bowel and/or mesenteric injury. ⢠A decision tree combining only two reproducible CT signs has high diagnostic performance for the diagnosis of surgical blunt bowel and/or mesenteric injury.