[Evaluation of resistance to transient occlusion of anterior mesenteric artery under the influence of the course of mineral water enriched with selenium (experimental research)]. / Otsenka ustoichivosti k tranzitornoi okklyuzii perednei bryzheechnoi arterii pod vliyaniem kursa mineral'noi vody, obogashchennoi selenom (eksperimental'noe issledovanie).

OBJECTIVE: To evaluate the effect of the preventive course of drinking mineral water enriched with selenium on the processes of resistance to the damaging action of reversible occlusion of the anterior mesenteric artery based on the comparison of intestinal morphological changes in the experiment. MATERIAL AND METHODS: There has been modeled ischemic reperfusion injury of the intestinal wall according to H. Ikeda and co-authors using reversible occlusion of the anterior mesenteric artery with 33 outbred male rats. The rats were divided into four groups by block randomization: the 1st group - intact animals (n=7) - without an exposure; the control group - sham operated animals (n=6); the group of comparison (n=7) - with a model-operation; the experimental group (n=11) - animals with a model operation that had courses of intragastric watering of bottled sulfate-chloride-hydrocarbonate-sodium low-mineralized (2.2 g/l) drinking mineral water «Psyzh¼ enriched with selenium. Biopsies of the small intestine were taken for histological examination. RESULTS: Histological examination of the small intestine of experimental animals determines various degrees of severity of damage: on average, the animals of the experimental group on the scale of C.J. Chiu (1970) had the lowest degree of severity of pathological changes, the animals of the group of comparison - 1.4 times higher (p=0.02). That is, the effect of a preventive course of mineral water «Psyzh¼ enriched with selenium was manifested in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery; in the presence of ischemic reperfusion damage to the intestinal wall, comparable in severity to changes with the animals without prevention, the most significant positive effect was realized in the containment of reactive changes. CONCLUSION: The effect of the preventive course of drinking mineral water «Psyzh¼ enriched with selenium manifested itself in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery, which is the basis for introducing this technique into clinical practice in order to prevent the development of reperfusion injuries of the intestine.

Diagnosis and therapeutic strategies for small bowel vascular lesions.

Small bowel vascular lesions, including angioectasia (AE), Dieulafoy's lesion (DL) and arteriovenous malformation (AVM), are the most common causes of obscure gastrointestinal bleeding. Since AE are considered to be venous lesions, they usually manifest as a chronic, well-compensated condition. Subsequent to video capsule endoscopy, deep enteroscopy can be applied to control active bleeding or to improve anemia necessitating blood transfusion. Despite the initial treatment efficacy of argon plasma coagulation (APC), many patients experience re-bleeding, probably because of recurrent or missed AEs. Pharmacological treatments can be considered for patients who have not responded well to other types of treatment or in whom endoscopy is contraindicated. Meanwhile, a conservative approach with iron supplementation remains an option for patients with mild anemia. DL and AVM are considered to be arterial lesions; therefore, these lesions frequently cause acute life-threatening hemorrhage. Mechanical hemostasis using endoclips is recommended to treat DLs, considering the high re-bleeding rate after primary APC cauterization. Meanwhile, most small bowel AVMs are large and susceptible to re-bleeding therefore, they usually require surgical resection. To achieve optimal diagnostic and therapeutic approaches for each type of small bowel lesion, the differences in their epidemiology, pathology and clinical presentation must be understood.

Active Hexose Correlated Compound Has Protective Effects in Ischemia-Reperfusion Injury of the Rat Small Intestine.

BACKGROUND: Ischemia-reperfusion (IR) injury of the small intestine is a serious problem in abdominal aortic aneurysm surgery or small intestine transplantation. Active hexose correlated compound (AHCC) is a popular anti-inflammatory drug in complementary and alternative medicine. The aim of this study was to examine whether pretreatment with AHCC reduces intestinal IR injury. METHODS: Rats were given a normal diet (IR group) or normal diet supplemented with 2% AHCC (IR + AHCC group) ad libitum for 10 d. After 1 d of fasting, the superior mesenteric artery was occluded by clipping for 45 min. Intestinal and blood samples were collected for 1-6 h after reperfusion. The messenger RNA (mRNA) and protein levels of inflammatory factors were analyzed. RESULTS: The IR + AHCC group had reduced mucosal abrasion and significantly increased mucosal thickness of the intestinal tissues 6 h after reperfusion, compared with the IR group. AHCC decreased mRNA expression of inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant 1 and interleukin 6 in the mucosa of the small intestine. AHCC also decreased expression of iNOS protein. Serum levels of cytokine-induced neutrophil chemoattractant 1 and tumor necrosis factor α were decreased in the IR + AHCC group compared with the IR group. Electrophoretic mobility shift assay of mucosal nuclear extracts revealed that AHCC inhibited the activation of nuclear factor kappa B. AHCC also inhibited the expression of iNOS antisense transcript, which stabilizes iNOS mRNA. CONCLUSIONS: Our findings suggest that AHCC reduces expression of inflammatory mediators, in part, by inhibiting nuclear factor kappa B activation. AHCC may have anti-inflammatory effect in patients with intestinal IR injury.

Dual-Energy CT Iodine Mapping and 40-keV Monoenergetic Applications in the Diagnosis of Acute Bowel Ischemia.

OBJECTIVE: Sensitivity of CT of the abdomen for detection of acute bowel ischemia (ABI) can be as low as 60%. In this study, we assessed the diagnostic performance of iodine-map and monoenergetic (40-keV) images in patients with suspected ABI. MATERIALS AND METHODS: This retrospective study included 60 consecutive patients with suspected ABI who underwent a standardized imaging protocol dual-source dual-energy CT (DECT) over a 26-month period. Clinical and operative outcomes were recorded as the reference standard. Two abdominal radiologists who were unaware of clinical and surgical information independently assessed conventional CT images for ABI. After a time interval designed to reduce recall, readers reassessed conventional images with supplementary iodine-map and 40-keV postprocessed images. Quantitative ROI analysis was also performed. RESULTS: ABI was observed in 11 patients. For reader A, sensitivity was 63.6% (95% CI, 30.8-89.1%) when interpreting conventional images alone. Sensitivity for detection of ABI increased to 81.8% (95% CI, 48.2-97.7%) and 100% (95% CI, 71.5-100%) when iodine-map and 40-keV images were assessed, respectively. For reader B, no change in sensitivity was seen with either technique, but the number of false-positives were reduced with supplementary iodine-map and 40-keV postprocessed images. Interobserver agreement was fair with conventional images (κ = 0.29) but improved to moderate (κ = 0.45) and substantial (κ = 0.63) with iodine-map and 40-keV images, respectively. Quantitative assessment found significant differences in iodine uptake (1.01 ± 0.55 mg/mL vs 3.04 ± 1.19 mg/mL) and mean attenuation (75.2 ± 38.4 HU vs 163.5 ± 48.9 HU) between nonischemic and ischemic segments, respectively. CONCLUSION: Iodine-map and 40-keV monoenergetic images increase conspicuity of ABI, resulting in improved diagnostic accuracy compared with review of conventional CT images alone.

Nicotinamide riboside has protective effects in a rat model of mesenteric ischaemia-reperfusion.

Acute mesenteric ischaemia is a syndrome caused by inadequate blood flow through the mesenteric vessels, resulting in ischaemia and eventual gangrene of the bowel wall. Although relatively rare, it is a potentially life-threatening condition. The maintenance of haemodynamic stability, along with adequate oxygen saturation, and the correction of any electrolyte imbalance, are of the utmost importance. However, nicotinamide adenine dinucleotide (NAD) biosynthesis modulation by precursor introduction can also be a powerful tool for preventing injury. Nicotinamide riboside is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to NAD+ . The present study investigated nicotinamide riboside's effect on endothelium functional state, microcirculation and intestinal morphology in acute mesenteric ischaemia and reperfusion. Mesenteric ischaemia was simulated after the adaptation period (15 minutes) by occluding the superior mesenteric artery for 60 minutes, followed by a reperfusion period of 30 minutes. The functional state of intestinal microcirculation was evaluated by laser Doppler flowmetry. Endothelial functional activity was studied by using wire myography. Intestinal samples were stained with haematoxylin and eosin for histological analysis. The results revealed that nicotinamide riboside protects the intestinal wall from ischaemia-reperfusion injury, as well as improving the relaxation function of mesenteric vessels. Nicotinamide riboside's protective effect in small intestine ischaemia-reperfusion can be used to reduce ischaemia-reperfusion injury, as well as to preserve intestinal grafts until transplant.

Autodigestion by migrated trypsin is a major factor in small intestinal ischemia-reperfusion injury.

BACKGROUND: The pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. MATERIALS AND METHODS: Mesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14.7 mg/kg), orlistat (5 mg/kg), and their combination or α1-proteinase inhibitor (60 mg/kg) were injected into the lumen of the small intestine. Systemic and vital parameters, intestinal microcirculation, and mucosal barrier function were monitored during the observation phase; markers of small intestinal injury, as well as trypsin-, chymotrypsin-, elastase-, and lipase-like activities in intestinal effluates were assessed at the end. RESULTS: The pattern of small intestinal injury correlated inversely with the local alterations in microvascular tissue perfusion and corresponded with the intestinal distribution of trypsin-like activity. Aprotinin almost completely inhibited trypsin-like activity (P < 0.05) and significantly reduced intestinal tissue injury. Combined with orlistat, it also increased the postischemic blood pressure (P < 0.05) but not the intestinal barrier function. Macroscopic as well as the histologic alterations were decreased by α1-proteinase inhibitor, which significantly improved postischemic blood pressure (P < 0.05). CONCLUSIONS: The I/R-induced pattern of small intestinal injury is likely to result from both local differences in tissue ischemia and the digestive activity of migrated pancreatic trypsin. Therefore, administration of aprotinin and orlistat into ischemic small intestines may be a therapeutic option in patients with a poor diagnosis.

Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different.

L-Arginine Modulates Intestinal Inflammation in Rats Submitted to Mesenteric Ischemia-Reperfusion Injury.

BACKGROUND: The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. METHODS: Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion. The total RNA was extracted and purified from samples of the small intestine. The concentration of each total RNA sample was determined by using spectrophotometry. The first-strand complementary DNA (cDNA) was synthesized in equal amounts of cDNA and the Master Mix SYBR Green qPCR Mastermix (SABiosciences, a Qiagen Company, Frederick, Md). Amounts of cDNA and Master Mix SYBR Green qPCR Mastermix were distributed to each well of the polymerase chain reaction microarray plate containing the predispensed gene-specific primer sets for Bax and Bcl2. Each sample was evaluated in triplicate, and the Student t test was applied to validate the homogeneity of each gene expression reaction (P < .05). RESULTS: The gene expression of Bax in IRG (+1.48) was significantly higher than in IRG-LARG (+9.69); the expression of Bcl2L1 in IRG (+1.01) was significantly higher than IRG-LARG (+22.89). CONCLUSIONS: The apoptotic cell pathway of 2 protagonists showed that LARG improves the gene expression of anti-apoptotic Bcl2l1 (Bcl2-like 1) more than the pro-apoptotic Bax (Bcl2-associated X protein).

Effects of Shenfu injection on macrocirculation and microcirculation during cardiopulmonary resuscitation.

AIM OF THE STUDY: To examine the effects of Shenfu injection (SFI) on macrocirculation and microcirculation during ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR). MATERIALS AND METHODS: Sixteen female Landrace pigs were used in this study. After anesthesia, coronary perfusion pressure (CPP) was measured, and then the abdominal cavity was opened to observe the mesenteric microcirculation with the aid of sidestream dark field imaging. Following the guidelines, we determined microvascular flow index, perfused vessel density and proportion of perfused vessels both for large (diameter>20 µm) and small (diameter<20 µm) microvessels. SFI (1 ml/kg) or saline was given by vein injection at 1h before inducing VF. CPR was initiated after 4 min VF. RESULTS: The shocks and duration of CPR were less in the SFI group compared with saline group. As the occurrence of VF, the CPP suddenly dropped to near zero, and cannot be measured in the both groups. However, there was greater CPP during CPR and at 1h after return of spontaneous circulation in the SFI group than saline group. Compared with saline, SFI significantly improved the microcirculation parameters of large and small microvessels during VF and CPR. CONCLUSIONS: SFI can improve the microvascular blood flow and CPP during VF and CPR, and reduce the shocks and duration of CPR.

Sodium tanshinone II A sulfonate ameliorates microcirculatory disturbance of small intestine by attenuating the production of reactie oxygen species in rats with sepsis.

OBJECTIVE: To examine whether sodium tanshinone II A sulfonate (STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species (ROS) in rats with sepsis. METHODS: A rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU, n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF) were determined by Western blotting. RESULTS: It was shown that there were obvious microcirculatory disturbance (P <0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury (P <0.01). CONCLUSION: STS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine.

AIM: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. RESULTS: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion-induced inflammatory reactions.

PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine (PC), may function as anti-inflammatory substances, but the mechanism remains largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated PC derivative, in a rodent model of small intestinal ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats were divided into control, mesenteric IR (45 min mesenteric artery occlusion, followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and microhaemodynamic parameters were measured; intestinal inflammatory markers (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver ATP contents were determined. RESULTS: The IR challenge reduced the intestinal intramural red blood cell velocity, increased the mesenteric vascular resistance, the tissue xanthine oxidoreductase activity, the superoxide production, and the nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous GPC attenuated the macro- and microcirculatory dysfunction and provided significant protection against the radical production resulting from the IR stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions in the mean arterial pressure and superior mesenteric artery flow, and similarly to the post-treatments with GPC, also decreased the xanthine oxidoreductase activity, the intestinal superoxide production, the nitrotyrosine level, and normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate the effectiveness of GPC therapies and provide indirect evidence that the anti-inflammatory effects of PC could be linked to a reaction involving the polar part of the molecule.

Attenuation of intestinal ischemic injury and shock by physostigmine.

BACKGROUND: Recently, protection in shock (hemorrhagic or septic) by physostigmine has been demonstrated. Here, we studied the protective effect of intravenous infusion of physostigmine in a rat model of severe intestinal ischemia-reperfusion (I/R) injury and shock. MATERIALS AND METHODS: Mesenteric I/R was induced in male Wistar rats by occlusion of the superior mesenteric artery (90 min) and subsequent reperfusion (120 min). Physostigmine (30 or 70 µg/kg) was administered as bolus injection before induction of I/R. One additional group received, subsequent to the bolus of 30-µg/kg physostigmine, a continuous infusion of 60-µg/kg physostigmine till the end of the experiment. RESULTS: Physostigmine at a dose of 70 µg/kg administered before I/R significantly decreased the macroscopically and microscopically visible intestinal damage. In addition to and presumably as a result of this local protective effect, physostigmine prevented shock induced by reperfusion of the ischemically injured intestine. Lower doses (30 µg/kg) or continuous application of physostigmine were less advantageous. CONCLUSIONS: Physostigmine is clearly protective in intestinal I/R injury and shock. However, for this purpose, physostigmine has to be applied at a dose (70 µg/kg), that is, approximately double the amount of the presently used clinical dose.

Isolating and using sections of bovine mesenteric artery and vein as a bioassay to test for vasoactivity in the small intestine.

Mammalian gastrointestinal systems are constantly exposed to compounds (desirable and undesirable) that can have an effect on blood flow to and from that system. Changes in blood flow to the small intestine can result in effects on the absorptive functions of the organ. Particular interest in toxins liberated from feedstuffs through fermentative and digestive processes has developed in ruminants as an area where productive efficiencies could be improved. The video associated with this article describes an in vitro bioassay developed to screen compounds for vasoactivity in isolated cross-sections of bovine mesenteric artery and vein using a multimyograph. Once the blood vessels are mounted and equilibrated in the myograph, the bioassay itself can be used: as a screening tool to evaluate the contractile response or vasoactivity of compounds of interest; determine the presence of receptor types by pharmacologically targeting receptors with specific agonists; determine the role of a receptor with the presence of one or more antagonists; or determine potential interactions of compounds of interest with antagonists. Through all of this, data are collected real-time, tissue collected from a single animal can be exposed to a large number of different experimental treatments (an in vitro advantage), and represents vasculature on either side of the capillary bed to provide an accurate picture of what could be happening in the afferent and efferent blood supply supporting the small intestine.

Hemorragia gastrointestinal, antiinflamatorios no esteroideos, ácido acetilsalicílico y anticoagulantes / Gastrointestinal bleeding, NSAIDs, aspirin and anticoagulants

Los estudios presentados en el reciente congreso de la American Gastroenterological Association, en el campo de la hemorragia digestiva alta no varicosa asociada o no a la toma de antiinflamatorios no esteroideos o de ácido acetilsalicílico, no han sido numerosos pero sí interesantes. Las conclusiones fundamentales son: a) rabeprazol, el único inhibidor de la bomba de protones que tenía escasos estudios en este campo, es eficaz en la prevención de úlceras gastroduodenales; b) famotidina podría ser también eficaz en la prevención de complicaciones por ácido acetilsalicílico; c) los nuevos y potentes inhibidores de ácido competitivos de la bomba de potasio son eficaces (tanto como los inhibidores de la bomba de protones) en la recurrencia de úlceras pépticas por ácido acetilsalicílico; d) la endoscopia precoz (< 8 h) en la hemorragia digestiva alta no varicosa no parece ofrecer mejor resultado que la efectuada en las primeras 24 h; e) la terapia endoscópica en Forrest 1 a no consigue obliterar la arteria sangrante en el 30% de las ocasiones y es la causa de la recurrencia; f) las terapias alternativas con pegamento o productos coagulantes se van abriendo paso en la terapia endoscópica del sangrante; g) la administración liberal de sangre en el sangrante digestivo se asocia a peor pronóstico; h) las lesiones del intestino delgado son causa frecuente de hemorragia digestiva cuando la endoscopia alta no demuestra estigmas positivos, y i) el estudio con cápsula endoscópica tiene un rendimiento alto en la hemorragia digestiva de origen oscuro si se efectúa precozmente en los 2 primeros días tras el inicio del episodio

The studies presented at the recent American Congress of Gastroenterology in the field of non-variceal upper gastrointestinal bleeding (associated or not to NSAIDs or ASA use) have not been numerous but interesting. The key findings are: a) rabeprazole, the only PPI that had few studies in this field, is effective in the prevention of gastric ulcers; b) famotidine could also be effective in the prevention of complications by AAS; c) the new competitive inhibitors of the acid potassium pump are effective (as much as PPIs) on the recurrence of peptic ulcers by ASA; d) early endoscop (<8 h) in non-variceal upper gastrointestinal bleeding seems to offer no better results than those made in the first 24 h; e) endoscopic therapy in Forrest 1a ulcers does not obliterate the bleeding artery in 30% of cases and is the cause of bleeding recurrence; f) alternative therapies with glue or clotting products are being increasingly used in endoscopic therapy of gastrointestinal bleeding; g) liberal administration of blood in the GI bleeding is associated with poor prognosis; h) lesions of the small intestine are frequent cause of gastrointestinal bleeding when upper endoscopy shows no positive stigmata; and i) capsule endoscopy studies have high performance in gastrointestinal bleeding of obscure origin, if performed early in the first two days after the beginning of the bleeding episode

Protection against intestinal injury from hemorrhagic shock by direct peritoneal resuscitation with pyruvate in rats.

OBJECTIVE: We explored the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock (HS). METHODS: Fifty rats were randomly assigned equally to five groups. In group sham, a surgical operation was performed on rats without shock or resuscitation. In group VR, rats were subjected only to VR. In groups NS, LA, and PY, direct peritoneal resuscitation was performed with normal saline (NS), lactate-based PDS (Lac-PDS), and pyruvate-based PDS (Pyr-PDS), respectively, after VR. Mean arterial pressure was monitored in the right common carotid artery. Two hours after resuscitation, the lactate level in arterial blood and the wet weight/dry weight ratio of the intestine were determined. The intestinal mucosal damage index was estimated, and ultrastructural changes in the intestinal mucosa were observed. Malondialdehyde, myeloperoxidase, nitric oxide, and tumor necrosis factor α levels were also measured. RESULTS: Two hours after HS and resuscitation, the increase in arterial blood lactate and intestinal wet weight/dry weight ratio declined significantly in rats from Groups LA and PY compared with groups VR and NS, whereas group PY was more advantageous in the changes of these parameters. The intestinal mucosal damage index and ultrastructural changes were also improved in groups LA and PY when compared with groups VR and NS. Protection was more apparent with Pyr-PDS than Lac-PDS. Hemorrhagic shock resulted in a significant increase in malondialdehyde levels and myeloperoxidase activity and was accompanied by overexpression of tumor necrosis factor α and a reduction in nitric oxide levels. These changes were significantly attenuated by Lac-PDS and Pyr-PDS at 2 h after resuscitation, and Pyr-PDS showed more effective protection for the intestine than Lac-PDS. CONCLUSIONS: Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS in its protective effect. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response, and regulation of intestinal mucosal blood flow and barrier function.

L-citrulline improves splanchnic perfusion and reduces gut injury during exercise.

PURPOSE: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. METHODS: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. RESULTS: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 ± 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs -2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, -185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability. CONCLUSIONS: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise.

Caffeic acid phenethyl ester alleviates mesenteric ischemia/reperfusion injury.

PURPOSE: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. METHODS: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 µmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 µmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. RESULTS: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). CONCLUSION: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.

Fish oil increases blood flow in the ileum during chronic feeding in rats.

Benefits of enteral feeding with immune-enhancing diets (IEDs) depend on route, timing, and composition. We hypothesized that chronic enteral feeding with certain individual immunonutrients would enhance gastrointestinal blood flow. Male rats were fed a standard enteral diet supplemented with immunonutrients for 5 days before study. Groups were (1) standard rat chow, (2) liquid control diet (CD) alone (CD), (3) CD + fish oil, (4) CD + L-arginine, and (5) CD + RNA fragments. Whole organ blood flow distribution was measured by colorimetric microsphere technique in antrum, small intestine (in thirds), colon, liver, spleen, pancreas, and kidneys. Chronic feeding for 5 days with CD + fish oil increased blood flow in the distal third of the small intestine compared with CD alone, whereas feeding with CD + L-arginine decreased blood flow in the small intestine (all segments) compared with CD alone. Acute gavage of CD + L-arginine or CD + fish oil increased blood flow in the proximal and middle third of the small intestine compared with CD alone. Control diet + RNA increased blood flow in the proximal small intestine compared with CD alone. These findings support prior acute feeding studies with CD, CD + individual immunonutrients, or IED. Our current data suggest that blood flow benefits associated with fish oil persist during chronic feeding in rats. Enhanced gastrointestinal perfusion might partially explain the benefits of early enteral feeding with IEDs not seen with regular enteral diets and parenteral immunonutrient delivery.

Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury.

OBJECTIVES: The usefulness of omega-3 lipid emulsions has been extensively studied. The objectives of the present study were to examine the effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury and the underlying mechanism. METHODS: A total of 66 rats were divided into three dietary groups (lipid-free, soybean oil, and fish oil groups). Each animal was administered total parenteral nutrition for 3 days, followed by induction of intestinal ischemia for 100 min. Animals subjected to sham surgery served as the controls. Intestinal tissue and blood were harvested 6 and 12 h after the surgery, then, assessment of the histological damage score, plasma-related parameters, and statistical evaluation were performed. RESULTS: The histological damage score in the intestinal tissues was significantly lower in the fish oil group than in the soybean oil group (P = 0.0121). The late-phase urinary level of 8-hydroxy-2-deoxyguanosine was also significantly lower in the fish oil group as compared with that in the other groups (P = 0.0267). Furthermore, the plasma level of high-mobility group box 1 protein was also significantly lower in the fish oil group as compared with that in the lipid-free group (P = 0.0398). CONCLUSION: It appeared that intravenous administration of an omega-3 lipid emulsion prior to ischemia-reperfusion injury reduced the oxidative stress and severity of tissue damage. Modification of membrane fatty acids may serve as the mechanism underlying this reduction of tissue damage.