Transmural cross-sectional findings and bowel damage assessment in preclinical Crohn's disease: a case-control study.

PURPOSE: Crohn's disease (CD) is a progressive disorder leading to cumulative bowel damage. The Lémann index is a validated tool that can help in monitoring the progression of the disease and evaluating the effectiveness of different therapies. Our aim was to describe the main radiological findings in incidentally diagnosed CD and to evaluate bowel damage in this subgroup compared to patients diagnosed at later stages. METHODS: Patients with an incidental diagnosis of CD during the colorectal cancer screening program were compared to controls with a CD cohort diagnosed after symptomatic onset and matched 1:1 by disease extent. All cross-sectional examinations were centrally read, performing a descriptive analysis of the main findings and calculation of Lémann index. RESULTS: Thirty-eight patients were included: 19 with preclinical CD (median age 55 years (IQR, 54-62), 53% male, 74% non-smokers; 74% B1 and 26% B2) and 19 matched-controls with symptomatic CD. In those with preclinical CD, the most frequent transmural findings on MRE were contrast enhancement (79%), wall thickening (79%), followed by lymphadenopathy (68%), edema (42%), and increased vascularity (42%). Among those with strictures, controls showed a higher rate of preestenotic dilation (100% vs. 0%, p = 0.01). Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p = 0.95). A statistically significant higher score in the colonic/rectum score was observed (p = 0.014). CONCLUSION: Patients with preclinical CD demonstrate similar radiological findings and degree of bowel damage as new-onset symptomatic CD.

Predictors of Survival Without Intestinal Resection after First-Line Endovascular Revascularization in Patients with Acute Arterial Mesenteric Ischemia.

Background Acute arterial mesenteric ischemia requires emergency treatment and is associated with high mortality rate and poor quality of life. Identifying factors associated with survival without intestinal resection (hereafter, intestinal resection-free [IRF] survival) could help in treatment decision-making after first-line endovascular revascularization. Purpose To identify factors associated with 30-day IRF survival in patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization. Materials and Methods Patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization because of a low probability of bowel necrosis were included in this single-center retrospective cohort (May 2014 to August 2022). Patient demographics, laboratory values, clinical characteristics at admission, CT scans, angiograms, and endovascular revascularization-related variables were included. The primary end point was 30-day IRF survival, and secondary end points were 3-month, 1-year, and 3-year overall survival. Factors independently associated with 30-day IRF survival were identified with binary logistic regression. Results A total of 117 patients (median age, 70 years [IQR, 60-77]; 53 female, 64 male) were included. Within 30 days after revascularization, 73 of 117 patients (62%) survived without resection, 28 of 117 (24%) survived after resection, 14 of 117 (12%) died without resection, and two of 117 (2%) underwent resection but died. The 30-day IRF survival was 63% (74 of 117). The 3-month, 1-year, and 3-year mortality rate was 18% (21 of 117), 21% (25 of 117), and 27% (32 of 117), respectively. Independent predictors of 30-day IRF survival were persistent bowel enhancement at initial CT (odds ratio [OR], 0.3; 95% CI: 0.2, 0.8; P = .013) and C-reactive protein (CRP) level less than 100 mg/L (OR, 0.3; 95% CI: 0.1, 0.8; P = .002). The 30-day IRF survival was 86%, 61%, 47%, and 23% in patients with both favorable features, persistent bowel enhancement but CRP level greater than 100 mg/L, no bowel enhancement but CRP level less than 100 mg/L, and both unfavorable features, respectively. Conclusion Independent predictors associated with 30-day IRF survival in patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization were persistent bowel wall enhancement at initial CT and CRP level less than 100 mg/L. © RSNA, 2024 Supplemental material is available for this article.

Effects of remote ischemic preconditioning on early markers of intestinal injury in experimental hemorrhage in rats.

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO2), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock.

High-resolution Visualization of Intestinal Microcirculation using Ultra-microangiography in Patients with Inflammatory Bowel Disease: A Pilot Study.

BACKGROUND AND AIMS: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA. METHODS: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control. RESULTS: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.

Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.

MCU inhibition protects against intestinal ischemia‒reperfusion by inhibiting Drp1-dependent mitochondrial fission.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

The Evaluation and Management of Intestinal Ischemia.

AbstractIntestinal ischemia can result from various pathologic conditions. The presentations of ischemia can range from acute to subacute and mild to severe. Diagnosis of this condition may pose challenges, particularly in the early, potentially salvageable, stages of disease. This review offers an evidence-based approach to understanding the diagnosis and management of inadequate intestinal perfusion.

Quantitative analysis of intestinal perfusion with indocyanine green (ICG) and methylene blue (MB) using a single clinically approved fluorescence imaging system: a demonstration in a porcine model.

BACKGROUND: Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB. METHODS: Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25 mg/kg-0.50 mg/kg MB was administered after 10 min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2 mg/kg) after 60 min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG. RESULTS: Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = - 0.7709; p = < 0.001; r = - 0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values. CONCLUSION: Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

Laser speckle flowgraphy has comparable accuracy to indocyanine green fluorescence angiography in assessing bowel blood perfusion.

PURPOSE: To investigate the accuracy of laser speckle flowgraphy (LSFG), a noninvasive method for the quantitative evaluation of blood flow using mean blur rate (MBR) as a blood flow parameter in the assessment of bowel blood perfusion compared to indocyanine green fluorescence angiography (ICG-FA). METHODS: We enrolled 46 patients who underwent left-sided colorectal surgery. LSFG and ICG-FA were applied to assess blood bowel perfusion, with MBR and luminance as parameters, respectively. In both measurement methods, the position where the parameter suddenly decreased was defined as the blood flow boundary line. Subsequently, the blood flow boundaries created after processing the blood vessels flowing into the intestinal tract were determined using LSFG and ICG-FA, and concordance between the two was examined. Blood flow boundaries were visually identified using color tone changes on a color map created based on MBR in LSFG and using differences in luminance in ICG-FA. The distances between the transection line and blood flow boundaries determined using each method were compared. RESULTS: The location of blood flow boundaries matched in 65% (30/46) of cases. Although locations differed in the remaining 35% (16/46), all were located on the anal side near the transection line, and the difference was not clinically significant. The average distances between the transection line and blood flow boundary were 2.76 (SD = 3.25) and 3.71 (SD = 4.26) mm, respectively. There was no statistically significant difference between the two groups (p = 0.38). CONCLUSION: LSFG was shown to have comparable accuracy to ICG-FA, and may be useful for evaluating bowel perfusion.

Surgical choice for the treatment of partial intestinal ischemic necrosis caused by acute type a aortic dissection combined with malperfusion of superior mesenteric artery.

Acute type A aortic dissection is a severe cardiovascular disease characterized by rapid onset and high mortality. Traditionally, urgent open aortic repair is performed after admission to prevent aortic rupture and death. However, when combined with malperfusion syndrome, the low perfusion of the superior mesenteric artery can further lead to intestinal necrosis, significantly impacting the surgery's prognosis and potentially resulting in adverse consequences, bringing. This presents great significant challenges in treatment. Based on recent domestic and international research literature, this paper reviews the mechanism, current treatment approaches, and selection of surgical methods for poor organ perfusion caused by acute type A aortic dissection. The literature review findings suggest that central aortic repair can be employed for the treatment of acute type A aortic dissection with inadequate perfusion of the superior mesenteric artery. The superior mesenteric artery can be windowed and (/or) stented, followed by delayed aortic repair. Priority should be given to revascularization of the superior mesenteric artery, followed by central aortic repair. During central aortic repair, direct blood perfusion should be performed on the distal true lumen of the superior mesenteric artery, leading to resulting in favorable therapeutic outcomes. The research results indicate that even after surgical aortic repair, intestinal ischemic necrosis may still occur. In such cases, prompt laparotomy and necessary necrotic bowel resection are crucial for saving the patient's life.

Abdominal Wall Closure in Intestinal and Multivisceral Transplantation: A State-Of-The-Art Review of Vascularized Abdominal Wall and Nonvascularized Rectus Fascia Transplantation.

Failure to close the abdomen after intestinal or multivisceral transplantation (Tx) remains a frequently occurring problem. Two attractive reconstruction methods, especially in large abdominal wall defects, are full-thickness abdominal wall vascularized composite allograft (AW-VCA) and nonvascularized rectus fascia (NVRF) Tx. This review compares surgical technique, immunology, integration, clinical experience, and indications of both techniques. In AW-VCA Tx, vascular anastomosis is required and the graft undergoes hypotrophy post-Tx. Furthermore, it has immunologic benefits and good clinical outcome. NVRF Tx is an easy technique without the need for vascular anastomosis. Moreover, a rapid integration and neovascularization occurs with excellent clinical outcome.

Irreversible Transmural Intestinal Necrosis in Acute Mesenteric Ischemia: Retrospective Cohort Study from a High-Volume Hospital.

Background: Owing to the low incidence rate and nonspecific symptoms of acute mesenteric ischemia (AMI), the identification and prediction of irreversible transmural intestinal necrosis (ITIN) and extensive bowel resection (≥100 cm) (EBR) are difficult and critical. This study aimed to investigate the risk factors for ITIN and EBR in patients with AMI. Methods: The clinical data of 254 AMI patients were retrospectively analyzed. Furthermore, the incidence of ITIN and EBR were set as dependent variables, and relevant risk factors were screened using univariate and multivariate logistic regression analyses. The comparisons of surgical characteristics and postoperative recovery outcomes between the EBR and control group were also conducted. Results: The presence of hemorrhagic (odds ratio [OR] = 28.356, P < .001) or other types ascites (OR = 13.051, P = .003), peritonitis (OR = 8.463, P = .005), intestinal diameter >2.35 cm (OR = 5.493, P = .020), and serum creatinine (CREA) >95 µmol/L (OR = 4.866, P = .048) were identified as independent risk factors for ITIN in patients with AMI. In addition, serum C-reactive protein (CRP) >15 mg/L (OR = 38.023, P = .006), and CREA >100 µmol/L (OR = 6.248, P = .035) were proved to be independently associated with EBR for ITIN cases. Compared to the control group, EBR significantly increased the likelihood of requiring enterostomy (P = .001), blood transfusion (P = .002), and transfer to intensive care unit (P = .016), while also prolonging the recovery time for intestinal function (P = .014). Conclusions: The presence of ascites, peritonitis, intestinal diameter >2.35 cm, and serum CREA >95 µmol/L were independently correlated with ITIN for AMI cases, while serum CRP >15 mg/L and CREA >100 µmol/L independently increased the risk of EBR.

PRMT6-FOXO3A ATTENUATES APOPTOSIS BY UPREGULATING PARKIN EXPRESSION IN INTESTINAL ISCHEMIA-REPERFUSION INJURY.

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.

Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis.

Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases. In this study, we synthesized two amphiphilic molecules, namely DTPA-N10-10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury.

EFFECTS OF HYPERBARIC OXYGEN THERAPY ON INTESTINAL ISCHEMIA-REPERFUSION AND ITS MECHANISM.

ABSTRACT: Ischemia can cause reversible or irreversible cell or tissue damage, and reperfusion after ischemia not only has no therapeutic effect but also aggravates cell damage. Notably, gut tissue is highly susceptible to ischemia-reperfusion (IR) injury under many adverse health conditions. Intestinal IR (IIR) is an important pathophysiological process in critical clinical diseases. Therefore, it is necessary to identify better therapeutic methods for relieving intestinal ischemia and hypoxia. Hyperbaric oxygenation refers to the intermittent inhalation of 100% oxygen in an environment greater than 1 atm pressure, which can better increase the oxygen level in the tissue and change the inflammatory pathway. Currently, it can have a positive effect on hypoxia and ischemic diseases. Related studies have suggested that hyperbaric oxygen can significantly reduce ischemia-hypoxic injury to the brain, spinal cord, kidney, and myocardium. This article reviews the pathogenesis of IR and the current treatment measures, and further points out that hyperbaric oxygen has a better effect in IR. We found that not only improved hypoxia but also regulated IR induced injury in a certain way. From the perspective of clinical application, these changes and the application of hyperbaric oxygen therapy have important implications for treatment, especially IIR.

INT-767-A Dual Farnesoid-X Receptor (FXR) and Takeda G Protein-Coupled Receptor-5 (TGR5) Agonist Improves Survival in Rats and Attenuates Intestinal Ischemia Reperfusion Injury.

Intestinal ischemia is a potentially catastrophic emergency, with a high rate of morbidity and mortality. Currently, no specific pharmacological treatments are available. Previous work demonstrated that pre-treatment with obeticholic acid (OCA) protected against ischemia reperfusion injury (IRI). Recently, a more potent and water-soluble version has been synthesized: Intercept 767 (INT-767). The aim of this study was to investigate if intravenous treatment with INT-767 can improve outcomes after IRI. In a validated rat model of IRI (60 min ischemia + 60 min reperfusion), three groups were investigated (n = 6/group): (i) sham: surgery without ischemia; (ii) IRI + vehicle; and (iii) IRI + INT-767. The vehicle (0.9% NaCl) or INT-767 (10 mg/kg) were administered intravenously 15 min after start of ischemia. Endpoints were 7-day survival, serum injury markers (L-lactate and I-FABP), histology (Park-Chiu and villus length), permeability (transepithelial electrical resistance and endotoxin translocation), and cytokine expression. Untreated, IRI was uniformly lethal by provoking severe inflammation and structural damage, leading to translocation and sepsis. INT-767 treatment significantly improved survival by reducing inflammation and preserving intestinal structural integrity. This study demonstrates that treatment with INT-767 15 min after onset of intestinal ischemia significantly decreases IRI and improves survival. The ability to administer INT-767 intravenously greatly enhances its clinical potential.

Gallic acid treatment protects intestinal tissue against ischaemia-reperfusion.

BACKGROUND: This study aimed to investigate the protective effects of gallic acid (GA) in the rat intestine against ischaemia-reperfusion (IR) injury. MATERIALS AND METHODS: Thirty male Wistar albino rats with a mean weight of 200-250 g were used. Animals were categorized into the sham, IR, and IR+GA groups. Ischaemia of the intestine was induced for 3 h by occluding the superior mesenteric artery (SMA) and then left for 3 h of reperfusion. In the IR+GA group, after ischaemia induction, 50 mg/kg GA was orally administered to the animals. Blood samples were collected for biochemical assays. Intestinal tissues were excised for histopathologic and immunohistochemical processing. RESULTS: Malondialdehyde (MDA) levels were increased, and catalase (CAT) and glutathione (GSH) levels were decreased in the IR group compared to the sham group. After GA treatment, MDA levels decreased and CAT and GSH levels increased in the GA-treated group compared to the IR group. In the sham group, normal intestinal histology was observed. In the IR group, the villi structures were completely degenerated. In the IR+GA group, histology was improved after GA treatment. In the sham group, the caspase-3 reaction was generally negative in the epithelium and glands. In the IR group, the caspase-3 reaction increased in apoptotic bodies and inflammatory cells. The caspase-3 reaction was negative in goblet cells and the epithelium. A moderate caspase-3 reaction was observed in the IR+GA group. The beclin-1 reaction was negative in epithelial cells and goblet cells in villi in the sham group. In the IR group, the beclin-1 reaction was positive in the degenerated villi. An intense beclin-1 reaction was also observed in some inflammatory cells. After GA treatment, the beclin-1 reaction was positive in a few cells. In general, moderate beclin-1 positivity was observed. CONCLUSIONS: Gallic acid, with its antioxidative effect, inhibited the apoptotic pathway (caspase-3) through beclin-1 regulation.

Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.

BACKGROUND: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H2O2, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H2O2, MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers. CONCLUSION: Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.

EFFECTS OF 2-METHYL-2-THIAZOLINE ON CIRCULATORY DYNAMICS AND INTESTINAL VASCULAR SYSTEM IN RABBITS WITH ENDOTOXIC SHOCK.

ABSTRACT: We hypothesized that circulatory and jejunal mucosal blood flow would improve after 2-methyl-2thiazoline (2MT) administration in endotoxic shock. This study aimed to evaluate changes in systemic circulation and in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time after administration of 2MT in rabbits with endotoxic shock. We created four groups (n = 6 each): control group, LPS (1 mg/kg) group, 2MT (80 mg/kg) group, and LPS-2MT group. As indicators of circulation, we measured MAP, heart rate, cardiac index, lactic acid level, SMV blood flow, and jejunal mucosal tissue blood flow every 30 min from 0 to 240 min. The drop in MAP observed in the LPS group was suppressed by 2MT administration. Superior mesenteric venous blood flow dropped temporarily with LPS administration but then rose thereafter. After administration of 2MT to the LPS group, SMV blood flow began to rise earlier than that in the LPS group and did not decline below that of the control group thereafter. In the LPS group, jejunal mucosal tissue blood flow transiently decreased and then increased but at a lower level than that in the control group. However, in the LPS-2MT group, although a transient decrease in jejunal mucosal tissue blood flow was observed, its flow then improved to the level of the control group. An interaction between 2MT and LPS was observed for jejunal mucosal tissue blood flow from 90 to 180 min and at 240 min (P < 0.05). We showed that 2MT maintained MAP and improved SMV blood flow and jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, 2MT had a positive effect on MAP and jejunal mucosal tissue blood flow.

Prognostic factors in patients with acute mesenteric ischemia-novel tools for determining patient outcomes.

BACKGROUND: Acute mesenteric ischemia (AMI) is a devastating disease with poor prognosis. Due to the multitude of underlying factors, prediction of outcomes remains poor. We aimed to identify factors governing diagnosis and survival in AMI and develop novel prognostic tools. METHODS: This monocentric retrospective study analyzed patients with suspected AMI undergoing imaging between January 2014 and December 2019. Subgroup analyses were performed for patients with confirmed AMI undergoing surgery. Nomograms were calculated based on multivariable logistic regression models. RESULTS: Five hundred and thirty-nine patients underwent imaging for clinically suspected AMI, with 216 examinations showing radiological indication of AMI. Intestinal necrosis (IN) was confirmed in 125 undergoing surgery, 58 of which survived and 67 died (median 9 days after diagnosis, IQR 22). Increasing age, ASA score, pneumatosis intestinalis, and dilated bowel loops were significantly associated with presence of IN upon radiological suspicion. In contrast, decreased pH, elevated creatinine, radiological atherosclerosis, vascular occlusion (versus non-occlusive AMI), and colonic affection (compared to small bowel ischemia only) were associated with impaired survival in patients undergoing surgery. Based on the identified factors, we developed two nomograms to aid in prediction of IN upon radiological suspicion (C-Index = 0.726) and survival in patients undergoing surgery for IN (C-Index = 0.791). CONCLUSION: As AMI remains a condition with high mortality, we identified factors predicting occurrence of IN with suspected AMI and survival when undergoing surgery for IN. We provide two new tools, which combine these parameters and might prove helpful in treatment of patients with AMI.