Apoptosis and brain ischaemia.

PubMed

Love, Seth

2003-04-01

There is increasing evidence that some neuronal death after brain ischaemia is mediated by the action of cysteine-requiring aspartate-directed proteases (caspases), the proteases responsible for apoptosis in mammals, although this form of neuronal death is not always accompanied by the morphological changes that are typical of apoptosis in other tissues. Caspase-mediated neuronal death is more extensive after transient than permanent focal brain ischaemia and may contribute to delayed loss of neurons from the penumbral region of infarcts. The activation of caspases after brain ischaemia is largely consequent on the translocation of Bax, Bak, and other BH3-only members of the Bcl-2 family to the mitochondrial outer membrane and the release of cytochrome c, procaspase-9, and apoptosis activating factor-1 (Apaf-1) from the mitochondrial intermembrane space. How exactly ischaemia induces this translocation is still poorly understood. NF-kappaB, the c-jun N-terminal kinase-c-Jun pathway, p53, E2F1, and other transcription factors are probably all involved in regulating the expression of BH3-only proteins after brain ischaemia, and mitochondrial translocation of Bad from sequestering cytosolic proteins is promoted by inactivation of the serine-threonine kinase, Akt. Other processes that are probably involved in the activation of caspases after brain ischaemia include the mitochondrial release of the second mitochondrial activator of caspases (Smac) or direct inhibitor-of-apoptosis-binding protein with low pI (DIABLO), the accumulation of products of lipid peroxidation, a marked reduction in protein synthesis, and the aberrant reentry of neurons into the cell cycle. Non-caspase-mediated neuronal apoptosis may also occur, but there is little evidence to date that this makes a significant contribution to brain damage after ischaemia. The intracellular processes that contribute to caspase-mediated neuronal death after ischaemia are all potential targets for therapy. However

Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model

PubMed Central

Corbett, A D; Lees, G M

1996-01-01

Since intermittent ischaemia may play an important role in the ætiology of Inflammatory Bowel Disease, particularly Crohn's Disease, a pharmacological model of neuronal ischaemia was applied to guinea-pig isolated intestinal preparations to mimic the acute effects of reduced blood flow on intestinal motility.Neuro-effector transmission and smooth muscle performance were examined in myenteric plexus-longitudinal muscle preparations of guinea-pig ileum exposed to sodium cyanide (NaCN), in order to inhibit oxidative phosphorylation, or to iodoacetic acid (IAA), to block glycolysis. Comparisons were made with the effects due to simple deprivation of oxygen or glucose.Depressions of cholinergic neuro-effector transmission induced by hypoxia or NaCN (effective concentration range 0.1–3 mM), given as separate treatments, singly or repetitively over 60–90 min, were apparent within 30 s and were reversible. The maximum inhibition was 90% and the IC50 for NaCN was 0.3 mM. A conspicuous component of these inhibitions was prejunctional.Non-cholinergic neuro-effector contractions were inhibited by up to 90% by anoxia or NaCN but recovery was incomplete and slower than with cholinergic contractions.Glucose-free solutions also caused a reversible failure of cholinergic neuro-effector transmission but of slower onset. In contrast, IAA (0.06–1 mM) abolished contractions irreversibly, apparently by a direct depressant effect on smooth muscle contraction. Unlike NaCN, IAA caused an initial potentiation of electrically-induced contractions, partly by a prejunctional potentiation of cholinergic neuro-effector transmission.It is concluded that a disruption of intestinal activity in pathological conditions associated with intestinal ischaemia may result from disturbances in the function of enteric neurones. PMID:9117084

Ischaemia-reperfusion injury: a major protagonist in kidney transplantation.

PubMed

Ponticelli, Claudio

2014-06-01

Ischaemia-reperfusion injury (IRI) is a frequent event in kidney transplantation, particularly when the kidney comes from a deceased donor. The brain death is usually associated with generalized ischaemia due to a hyperactivity of the sympathetic system. In spite of this, most donors have profound hypotension and require administration of vasoconstrictor agents. Warm ischaemia after kidney vessels clamping and the cold ischaemia after refrigeration also reduce oxygen and nutrients supply to tissues. The reperfusion further aggravates the state of oxidation and inflammation created by ischaemia. IRI first attacks endothelial cells and tubular epithelial cells. The lesions may be so severe that they lead to acute kidney injury (AKI) and delayed graft function (DGF), which can impair the graft survival. The unfavourable impact of DGF is worse when DGF is associated with acute rejection. Another consequence of IRI is the activation of the innate immunity. Danger signals released by dying cells alarm Toll-like receptors that, through adapter molecules and a chain of kinases, transmit the signal to transcription factors which encode the genes regulating inflammatory cells and mediators. In the inflammatory environment, dendritic cells (DCs) intercept the antigen, migrate to lymph nodes and present the antigen to immunocompetent cells, so activating the adaptive immunity and favouring rejection. Attempts to prevent IRI include optimal management of donor and recipient. Calcium-channel blockers, l-arginine and N-acetylcysteine could obtain a small reduction in the incidence of post-transplant DGF. Fenoldopam, Atrial Natriuretic Peptide, Brain Natriuretic Peptide and Dopamine proved to be helpful in reducing the risk of AKI in experimental models, but there is no controlled evidence that these agents may be of benefit in preventing DGF in kidney transplant recipients. Other antioxidants have been successfully used in experimental models of AKI but only a few studies of poor

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice.

PubMed

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-10-01

There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.

Combined Impact of Chronic Kidney Disease and Contrast Induced Acute Kidney Injury on Long-term Outcomes in Patients with Acute Lower Limb Ischaemia.

PubMed

Zlatanovic, Petar; Koncar, Igor; Dragas, Marko; Ilic, Nikola; Sladojevic, Milos; Mutavdzic, Perica; Tomic, Ivan; Kostic, Dusan; Davidovic, Lazar

2018-07-01

Acute lower limb ischaemia (ALI) is the sudden onset of decreased arterial perfusion with imminent threat to limb viability. Contrast induced acute kidney injury (CI-AKI) is one of the complications that increases mortality in patients who undergo contrast imaging in coronary procedures. The goal of this study is to evaluate the impact of chronic kidney disease (CKD) and CI-AKI on long-term clinical outcomes in patients with ALI undergoing lower limb revascularisation. A total 1017 consecutive patients with acute lower limb ischaemia who were admitted between July 1, 2006, and January 1, 2017, were retrospectively reviewed. Patients who had end stage renal disease, those who had end stage heart and malignant disease and died within 7 days of limb revascularisation, and those who did not undergo angiography were excluded. Thus 546 patients were included in the final analysis. Patients were classified as with or without CKD and were then subdivided according to the presence or absence of the development of CI-AKI, defined as an increase in serum creatinine of ≥0.5 mg/dL or by ≥25% from the baseline value within the first 72 h after contrast exposure. The primary end point was all cause mortality and secondary major adverse limb event (MALE). Both CKD and CI-AKI were associated with the highest rate of all cause mortality (chi square = 55.77, d.f. = 1, p < .01, log rank test) and MALE (chi square = 79.07, d.f. = 1, p < .01, log rank test). The presence of CKD and CI-AKI were significant risk factors associated with long-term all cause mortality (HR = 2.61, p < .01) and MALE (HR = 2.87, p < .01). In patients with ALI undergoing lower limb revascularisation, both CKD and CI-AKI were significantly associated with poor long-term outcomes compared with either CKD or CI-AKI alone. Further studies are required to assess this association and to confirm the combined effect of CKD and CI-AKI on long-term clinical outcomes. Copyright © 2018 European

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice

PubMed Central

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-01-01

Background There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Methods Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Results Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. Conclusion In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction. PMID:28357012

PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury?

PubMed Central

Mocanu, M M; Yellon, D M

2007-01-01

Myocardial ischaemia/reperfusion injury leading to myocardial infarction is one of the most frequent causes of debilitation and death in man. Considerable research has been undertaken to investigate the possibility of reducing myocardial infarction and increasing cell survival by activating certain endogenous prosurvival signaling pathways. Thus, it has been established that the activation of the PI3K (Phosphoinositide-3 kinase)/Akt (Protein kinase B, PKB) signaling pathway is essential for protection against ischaemia/reperfusion injury. This pathway has been shown to be activated by mechanical procedures (e.g. pre and post conditioning) as well as by a number of pharmacological agents. Although the activation of this prosurvival signaling pathway induces the phosphorylation of a large number of substrates implicated in increased cell survival, when activated over a prolonged period this pathway can have detrimental consequences by facilitating unwanted growth and malignancies. Importantly PTEN (phosphatase and tensin homolog deleted on chromosome ten), is the main phosphatase which negatively regulates the PI3K/Akt pathway. In this review we discuss: a) the significance and the limitations of inhibiting PTEN in myocardial ischaemia/reperfusion injury; b) PTEN and its relationship to ischaemic preconditioning, c) the role of PTEN in the development of tolerance to chronic administration of drugs known to limit infarction by activating PI3K/Akt pathway when given acutely, and d) the possible role of PTEN in the ischaemic/reperfused diabetic heart. The experimental evidence discussed in this review illustrates the importance of PTEN inhibition in the protection of the heart against ischaemia/reperfusion injury. PMID:17293884

[Mesenteric flow in an experimental model of ischaemia-reperfusion in rats].

PubMed

Cáceres, F; Castañon, M; Lerena, J; Cusi, V; Badosa, J; Morales, L

2014-03-01

Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intra-abdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<.01) when associated with the MVH (rs = -0,495; rs = -0,452; rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518). The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Kcne2 deletion attenuates acute post-ischaemia/reperfusion myocardial infarction

PubMed Central

Hu, Zhaoyang; Crump, Shawn M.; Zhang, Ping; Abbott, Geoffrey W.

2016-01-01

Aims Most cardiac arrhythmia-associated genes encode ion channel subunits and regulatory proteins that are also expressed outside the heart, suggesting that diseases linked to their disruption may be multifactorial. KCNE2 is a ubiquitously expressed potassium channel β subunit associated with cardiac arrhythmia, atherosclerosis, and myocardial infarction (MI) in human populations. Here, we tested the hypothesis that Kcne2 disruption in mice would influence the acute outcome of experimentally induced MI. Methods and results One-year-old male Kcne2+/+ and Kcne2−/− mice were subjected to cardiac ischaemia/reperfusion injury (IRI) by left anterior descending coronary artery ligation. After reperfusion (3 h), infarct size and markers of tissue damage were quantified. Unexpectedly, post-reperfusion, Kcne2−/− mice exhibited 40% lower infarct size, decreased myocardial apoptosis and damage, and more than two-fold lower serum levels of damage markers, lactate dehydrogenase and creatine kinase, than Kcne2+/+ mice. Kcne2 deletion, despite increasing normalized heart weight and prolonging baseline QTc by 70%, helped preserve post-infarct cardiac function (quantified by a Millar catheter), with parameters including left ventricular maximum pressure, max dP/dt (P < 0.01), contractility index, and pressure/time index (P < 0.05) all greater in Kcne2−/− compared with Kcne2+/+ mice. Western blotting indicated two-fold-increased glycogen synthase kinase 3β (GSK-3β) phosphorylation (inactivation) before and after IRI (P < 0.05) in Kcne2−/− mice compared with Kcne2+/+ mice. GSK-3β inhibition by SB216763 mimicked in Kcne2+/+ mice the cardioprotective effects of Kcne2 deletion, but did not further enhance them in Kcne2−/− mice, suggesting that GSK-3β inactivation was a primary cardioprotective mechanism arising from Kcne2 deletion. Conclusions Kcne2 deletion preconditions the heart, attenuating the acute tissue damage caused by an imposed IRI. The findings

Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

PubMed Central

Castro, R R T; Porphirio, G; Serra, S M; Nóbrega, A C L

2004-01-01

Objective: To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease. Design: Double blind, randomised, placebo controlled, crossover study. Setting: Outpatients evaluated in an exercise test laboratory. Patients: 15 patients with exercise induced myocardial ischaemia. Interventions: Maximal cardiopulmonary exercise test on a treadmill according to an individualised ramp protocol on three days. The first day was used for adaptation to the equipment and to determine exercise tolerance and the presence of exercise induced ischaemia. On the other two days, the cardiopulmonary exercise test was performed two hours after oral administration of pyridostigmine (45 mg) or placebo. All patients were taking their usual medication during the experiments. Main outcome measures: Rate–pressure product and oxygen uptake during exercise. Results: Pyridostigmine inhibited the submaximum chronotropic response (p  =  0.001), delaying the onset of myocardial ischaemia, which occurred at a similar rate–pressure product (mean (SE) placebo 20.55 (1.08) mm Hg × beats/min 103; pyridostigmine 19.75 (1.28) mm Hg × beats/min 103; p  =  0.27) but at a higher exercise intensity (oxygen consumption: placebo 18.6 (1.7) ml/kg/min; pyridostigmine 19.6 (1.8) ml/kg/min; p  =  0.03). Also, pyridostigmine increased peak oxygen consumption (placebo 23.6 (2) ml/kg/min; pyridostigmine 24.8 (2) ml/kg/min; p  =  0.01) and peak oxygen pulse (placebo 12.9 (1) ml/beat; pyridostigmine 13.6 (1) ml/beat; p  =  0.02). Conclusions: Pyridostigmine improved peak exercise tolerance and inhibited the chronotropic response to submaximum exercise, increasing the intensity at which myocardial ischaemia occurred. These results suggest that pyridostigmine can protect against exercise induced myocardial ischaemia. PMID:15367503

Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

PubMed Central

VIZZOTTO, LAURA; VERTEMATI, MAURIZIO; DEGNA, CARLO TOMMASINI; ASENI, PAOLO

2001-01-01

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients. PMID:11430699

Protection of pulmonary graft from thrombosis in donation after cardiac death: effect of warm ischaemia versus cold ischaemia.

PubMed

Pierre, Leif; Lindstedt, Sandra; Ingemansson, Richard

2016-11-01

The use of donation after cardiac death (DCD) to overcome organ shortage is slowly moving into the clinic. In this study, we compare the protective effect of warm ischaemia versus cold ischaemia on thrombotic formation in non-heparinized pulmonary grafts. Twelve Landrace pigs were randomized into two groups: warm ischaemia and cold ischaemia. Ventricular fibrillation without the administration of heparin was induced to mimick an uncontrolled DCD situation. The animals were then exposed to either 1 h of cold ischaemia (insertion of drain and installation of cold fluid in the pleuras) or warm ischaemia (body temperature). After 1 h, the pulmonary artery was opened and the pulmonary arterial branches were then macroscopically studied for thrombotic material. After 60 min, the temperature was 36.6 ± 0.0°C in the warm ischaemic group and 14.6 ± 0.1°C in the cold ischaemic group (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the pulmonary artery in the animals examined and in the cold ischaemic group 6.8 ± 0.2 ml thrombotic material was found in the pulmonary artery (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the arterial branches of the pulmonary artery and in the cold ischaemic group 2.3 ± 0.1 ml thrombotic material was found in the arterial branches of the pulmonary artery (P < 0.001). Warm ischaemia rather than cold ischaemia seems to protect the pulmonary graft from thrombosis in uncontrolled non-heparinized DCD pigs. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Detrimental effects of acute hyperglycaemia on the rat heart.

PubMed

Mapanga, R F; Joseph, D; Symington, B; Garson, K-L; Kimar, C; Kelly-Laubscher, R; Essop, M Faadiel

2014-03-01

Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways (NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection. We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Effects of defibrotide, a novel oligodeoxyribonucleotide, on ischaemia and reperfusion injury of the rat liver.

PubMed

Kim, Kwang Joon; Shin, Yong Kyoo; Song, Jin Ho; Oh, Byung Kwon; Choi, Myung Sup; Sohn, Uy Dong

2002-02-01

1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.

Duodenal Obstruction Caused by Acute Appendicitis with Intestinal Malrotation in a Child.

PubMed

Biçer, Şenol; Çelik, Ali

2015-08-27

In patients with intestinal malrotation, the diagnosis of acute appendicitis can be difficult due to atypical presentation. Duodenal obstruction caused by acute appendicitis with the presence of malrotation has rarely been reported in children. We report the case of a 14-year-old male patient with bilious vomiting and abdominal distension. A diagnosis could not be made by computed tomography, ultrasonography, or endoscopy. We observed a dilated stomach and malrotation in laparotomy. The caecum was in the right upper quadrant, and an inflamed appendix was located in the subhepatic region. After the appendectomy, the cecum was mobilized and fixed in the right lower quadrant. In children with intestinal malrotation, acute appendicitis can present as duodenal obstruction without abdominal pain, and standard imaging methods can miss the correct diagnosis.

The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease.

PubMed

Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

2015-01-01

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia

PubMed Central

Kalappa, Bopanna I; Sun, Fen; Johnson, Stephen R; Jin, Kunlin; Uteshev, Victor V

2013-01-01

Background and Purpose Activation of α7 nicotinic acetylcholine receptors (nAChRs) can be neuroprotective. However, endogenous choline and ACh have not been regarded as potent neuroprotective agents because physiological levels of choline/ACh do not produce neuroprotective levels of α7 activation. This limitation may be overcome by the use of type-II positive allosteric modulators (PAMs-II) of α7 nAChRs, such as 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea (PNU-120596). This proof-of-concept study presents a novel neuroprotective paradigm that converts endogenous choline/ACh into potent neuroprotective agents in cerebral ischaemia by inhibiting α7 nAChR desensitization using PNU-120596. Experimental Approach An electrophysiological ex vivo cell injury assay (to quantify the susceptibility of hippocampal neurons to acute injury by complete oxygen and glucose deprivation; COGD) and an in vivo middle cerebral artery occlusion model of ischaemia were used in rats. Key Results Choline (20–200 μM) in the presence, but not absence of 1 μM PNU-120596 significantly delayed anoxic depolarization/injury of hippocampal CA1 pyramidal neurons, but not CA1 stratum radiatum interneurons, subjected to COGD in acute hippocampal slices and these effects were blocked by 20 nM methyllycaconitine, a selective α7 antagonist, thus, activation of α7 nAChRs was required. PNU-120596 alone was ineffective ex vivo. In in vivo experiments, both pre- and post-ischaemia treatments with PNU-120596 (30 mg·kg−1, s.c. and 1 mg·kg−1, i.v., respectively) significantly reduced the cortical/subcortical infarct volume caused by transient focal cerebral ischaemia. PNU-120596 (1 mg·kg−1, i.v., 30 min post-ischaemia) remained neuroprotective in rats subjected to a choline-deficient diet for 14 days prior to experiments. Conclusions and Implications PNU-120596 and possibly other PAMs-II significantly improved neuronal survival in cerebral ischaemia by augmenting

Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options.

PubMed

Linnemann, Birgit; Erbe, Matthias

2016-01-01

The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a

[Adult intestinal malrotation associated with intestinal volvulus].

PubMed

Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen

Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Profound loss of intestinal Tregs in acutely SIV-infected neonatal macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Shen, Chanjuan; Alvarez, Xavier; Liu, David; Pahar, Bapi; Ratterree, Marion S; Doyle-Meyers, Lara A; Lackner, Andrew A; Veazey, Ronald S

2015-02-01

Impairment of the intestinal mucosal immune system is an early feature of HIV-infected children. Most infected children exhibit clinical gastrointestinal symptoms at some stage of infection, and persistent diarrhea is a marker for rapid disease progression. It is known that Tregs are especially important in mediating intestinal immune homeostasis and that loss of this subset may result in intestinal inflammation and associated clinical signs. Large numbers of FoxP3(+) T cells were found in all tissues in newborn macaques, which coexpressed high levels of CD25 and CD4, indicating that they were Tregs. Moreover, neonates had much greater percentages of Tregs in intestinal tissues compared with peripheral lymphoid tissues. After SIV infection, a significant loss of Tregs was detected in the intestine compared with age-matched normal infants. Finally, SIV-infected FoxP3(+) T cells were detected in tissues in neonates as early as 7 SIV dpi. These results demonstrate that Tregs constitute a significant fraction of CD4(+) T cells in neonatal intestinal tissues and that an early, profound loss of Tregs occurs in acute SIV infection, which may contribute to the intestinal disorders associated with neonatal HIV infection. © Society for Leukocyte Biology.

Quaternion-based study of angular velocity of the cardiac vector during myocardial ischaemia.

PubMed

Cruces, Pablo Daniel; Arini, Pedro David

2017-12-01

Early detection of acute ischaemia through non-invasive methods remains a challenge in health research. Ischaemic condition caused by a decrease in the blood supply in a cardiac region induces hypoxia and metabolic abnormalities that contribute to the electrical instability of the heart and to the development of slow conduction in damaged tissue. Herein, a percutaneous transluminal coronary angiography (PTCA) is considered as a model of supply ischaemia. We use the concept of quaternion to develop a robust method for assessing the angular velocity of cardiac vector in the orthogonal XYZ leads obtained from 92 patients undergoing the PTCA procedure. The maxima of angular velocity in both ventricular depolarization and repolarization are combined with traditional linear velocity indexes in order to obtain a detector of ischaemic episodes (Ischaemia Detector, ID). ID achieves 98%/100% of sensitivity/specificity when differentiating healthy subjects from patients with early ischaemia. Furthermore, it also shows high accuracy when the comparison is made between ischaemic subjects and patients with different non-ischaemic pathologic ST-deviations which are known to cause false positives, reaching 95%/98% of sensitivity/specificity. Moreover, the study of significant reductions (p<0.001) of angular velocity components allows extraction of distinct ischaemic common features which are useful for analyzing the dependence of vectorcardiogram signal on each site of occlusion. The sensitivity of injury location reaches values of 88% (RCA), 87% (LAD) and 80% (LCx). The high performance of the proposed method establishes a promising outcome for application in computerized assistance in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute intestinal obstruction due to metastatic lung cancer—case report

PubMed Central

2017-01-01

Abstract We present a case of male patient, who was referred to our department because of acute intestinal obstruction, which was the initial clinical symptom of primary lung cancer. The abdominal computed tomography (CT) prior to the emergency operation showed small intestinal obstruction and metastases to both adrenal glands. The patient underwent an emergency abdominal exploratory laparotomy, that confirmed small bowel obstruction and diffuse metastatic lesions along the entire small bowel length. During the operation we took a sample of one metastasis for pathological examination and we created an intestinal bypass to relieve small bowel obstruction. The pathologist suspected to primary lung cancer according to the immunohistochemical staining. The chest CT after the emergency operation showed a large primary tumor in the left upper pulmonary lobe. PMID:28458837

Does the Intestinal Parasite Enterobius vermicularis Cause Acute Appendicitis?

PubMed

Pirhan, Yavuz; Özen, Fatma Zeynep; Kılınç, Çetin; Güçkan, Rıdvan

2017-06-01

Although intestinal parasitic infections rarely cause acute appendicitis, they are common public health problems in undeveloped and developing countries. Parasitic infections should be kept in mind in patients clinically suspected of having acute appendicitis, and treatment procedures should be adopted according to the etiology. Herein we presented the cases of four patients with clinical findings of acute appendicitis. Patients were clinically suspected of having acute appendicitis, and Enterobius vermicularis was detected in the pathological examinations of specimens. Pinworm infections are common parasitic infections that may mimic appendicitis. The pathology of the four cases was noted when the file of 186 patients aged between 4 and 72 years who underwent surgery for acute appendicitis in my hospital was retrospectively reviewed. When the appendectomy specimen was examined histopathologically it was understood that acute appendicitis was caused by Enterobius vermicularis parasite. In Enterobius infections, performing systemic therapy for patients and their family members is sufficient. To prevent unnecessary appendectomy, this type of infection should be made to ask in the history and clinical findings of patients.

The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

PubMed Central

Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

2015-01-01

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed. PMID:26090477

Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury

PubMed Central

Wang, Yuhua; Liu, Yanlong; Sidhu, Anju; Ma, Zhenhua; McClain, Craig

2012-01-01

Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (109 colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel

The Small Intestine in Experimental Acute Iron Poisoning

PubMed Central

Hosking, C. S.

1971-01-01

A histological examination of the small intestine of rats following acute iron poisoning by ingestion of ferrous sulphate solution is presented. The changes that occur depend on the dose and can be broadly divided into 2 classes. When a very large dose is given (greater than 0·3 mg. Fe/g.), there is gross shrinkage of the villi, sub-epithelial oedema and eventual loss of epithelium. With doses less than 0·2 mg. Fe/g., contraction of villi was not so obvious, but as the animals survive longer with the lower dose, the changes often progressed to gross destruction of the villous stalk. Some of the animals given smaller doses survived and in those that were killed after 24 hr, the mucosa of the small intestine was essentially normal. ImagesFigs. 1-4Figs. 5-7Figs. 8-11 PMID:5547659

Evaluation of acute toxicity and intestinal transit time of Olax scandens Roxb. leaves.

PubMed

Naik, Raghavendra; Acharya, Rabinarayan; Nariya, Mukesh B; Borkar, Sneha D

2015-01-01

Olax scandens Roxb. is a shrub or small tree found throughout tropical India. Fruits and leaves of this plant are used for medicinal and food purpose. Traditionally, leaves of O. scandens are used as vegetable in constipation. To evaluate the acute toxicity and intestinal transit time of O. scandens leaves on experimental animals. Acute oral toxicity study for sample was carried out following OECD guidelines. Evaluation of intestinal transit time was carried out in the dose of 1300 mg/kg by adopting Kaolin expulsion test and latency of the onset of kaolin expulsion in fecal matter in mice. The results show that the test drug is not likely to produce any toxicity in higher dose. In kaolin expulsion test, the drug produced mild increase in intestinal motility in mice proved by fast clearance of kaolin pellet in comparison to control group. The leaves of O. scandens are safe at higher dose and showed mild laxative activity in the dose of 1300 mg/kg body weight of mice.

Pituitary adenylate cyclase-activating polypeptide ameliorates experimental acute ileitis and extra-intestinal sequelae.

PubMed

Heimesaat, Markus M; Dunay, Ildiko R; Schulze, Silvia; Fischer, André; Grundmann, Ursula; Alutis, Marie; Kühl, Anja A; Tamas, Andrea; Toth, Gabor; Dunay, Miklos P; Göbel, Ulf B; Reglodi, Dora; Bereswill, Stefan

2014-01-01

The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) plays pivotal roles in immunity and inflammation. So far, potential immune-modulatory properties of PACAP have not been investigated in experimental ileitis. Mice were perorally infected with Toxoplasma (T.) gondii to induce acute ileitis (day 0) and treated daily with synthetic PACAP38 from day 1 to 6 post infection (p.i.; prophylaxis) or from day 4 to 6 p.i. (therapy). Whereas placebo-treated control mice suffered from acute ileitis at day 7 p.i. and succumbed to infection, intestinal immunopathology was ameliorated following PACAP prophylaxis. PACAP-treated mice exhibited increased abundance of small intestinal FOXP3+ cells, but lower numbers of ileal T lymphocytes, neutrophils, monocytes and macrophages, which was accompanied by less ileal expression of pro-inflammatory cytokines such as IL-23p19, IL-22, IFN-γ, and MCP-1. Furthermore, PACAP-treated mice displayed higher anti-inflammatory IL-4 concentrations in mesenteric lymph nodes and liver and higher systemic anti-inflammatory IL-10 levels in spleen and serum as compared to control animals at day 7 p.i. Remarkably, PACAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments as indicated by reduced pro-inflammatory mediator levels in spleen (TNF-α, nitric oxide) and liver (TNF-α, IFN-γ, MCP-1, IL-6) and less severe histopathological sequelae in lungs and kidneys following prophylactic PACAP treatment. Strikingly, PACAP prolonged survival of T. gondii infected mice in a time-of-treatment dependent manner. Synthetic PACAP ameliorates acute small intestinal inflammation and extra-intestinal sequelae by down-regulating Th1-type immunopathology, reducing oxidative stress and up-regulating anti-inflammatory cytokine responses. These findings provide novel potential treatment options of inflammatory bowel diseases.

Acute Upper Gastro-Intestinal Bleeding in Morocco: What Have Changed?

PubMed Central

Timraz, A.; Khannoussi, W.; Ajana, F. Z.; Essamri, W.; Benelbarhdadi, I.; Afifi, R.; Benazzouz, M.; Essaid, A.

2011-01-01

Objective. In the present study, we aimed to investigate epidemiological, clinical, and etiological characteristics of acute upper gastro-intestinal bleeding. Materials and Methods. This retrospective study was conducted between January 2003 and December 2008. It concerned all cases of acute upper gastroduodenal bleeding benefited from an urgent gastro-intestinal endoscopy in our department in Morocco. Characteristics of patients were evaluated in terms of age, gender, medical history, presenting symptoms, results of rectal and clinical examinations, and endoscopy findings. Results. 1389 cases were registered. As 66% of the patients were male, 34% were female. Mean age was 49. 12% of patients had a history of previous hemorrhage, and 26% had a history of NSAID and aspirin use. Endoscopy was performed in 96%. The gastroduodenal ulcer was the main etiology in 38%, followed by gastritis and duodenitis in 32.5%. Conclusion. AUGIB is still a frequent pathology, threatening patients' life. NSAID and aspirin are still the major risk factors. Their impact due to peptic ulcer remains stable in our country. PMID:21991509

A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

DTIC Science & Technology

2016-08-01

Acronyms and Symbols ARA Applied Research Associates, Inc. ARS Acute radiation syndrome d Days DE Differential Evolution DTRA Defense Threat...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...epithelial cells to acute radiation alone. The model has been modified for improved radiation response, and an addition to the model allows for thermal injury

p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia–reperfusion

PubMed Central

Wu, Bin; Qiu, Wei; Wang, Peng; Yu, Hui; Cheng, Tao; Zambetti, Gerard P; Zhang, Lin; Yu, Jian

2007-01-01

Background The small intestine is highly sensitive to ischaemia–reperfusion (I/R) induced injury which is associated with high morbidity and mortality. Apoptosis, or programmed cell death, is a major mode of cell death occurring during I/R induced injury. However, the mechanisms by which I/R cause apoptosis in the small intestine are poorly understood. p53 upregulated modulator of apoptosis (PUMA) is a p53 downstream target and a member of the BH3‐only group of Bcl‐2 family proteins. It has been shown that PUMA plays an essential role in apoptosis induced by a variety of stimuli in different tissues through a mitochondrial pathway. Aims The role of PUMA in I/R induced injury and apoptosis in the small intestine was investigated. The mechanisms by which PUMA is regulated in I/R induced intestinal apoptosis were also studied. Methods Ischaemia was induced by superior mesenteric artery occlusion in the mouse small intestine. Induction of PUMA in response to ischaemia alone, or ischaemia followed by reperfusion (I/R), was examined. I/R induced intestinal apoptosis and injury were compared between PUMA knockout and wild‐type mice. The mechanisms of I/R induced and PUMA mediated apoptosis were investigated through analysis of caspase activation, cytosolic release of mitochondrial cytochrome c and alterations of the proapoptotic Bcl‐2 family proteins Bax and Bak. To determine whether PUMA is induced by reactive oxygen species and/or reactive nitrogen species generated by I/R, superoxide dismutase (SOD) and N‐nitro‐L‐arginine methyl ester (L‐NAME) were used to treat animals before I/R. To determine whether p53 is involved in regulating PUMA during I/R induced apoptosis, PUMA induction and apoptosis in response to I/R were examined in p53 knockout mice. Results PUMA was markedly induced following I/R in the mucosa of the mouse small intestine. I/R induced intestinal apoptosis was significantly attenuated in PUMA knockout mice compared with that in wild�

Lethal pneumatosis coli in a 12-month-old child caused by acute intestinal gas gangrene after prolonged artificial nutrition: a case report

PubMed Central

Kircher, Stefan; Wössner, Rupert; Müller-Hermelink, Hans-Konrad; Völker, Hans-Ullrich

2008-01-01

Introduction Pneumatosis coli is a rare disease with heterogeneous symptoms which can be detected in the course of various acute and chronic intestinal diseases in children, such as necrotizing enterocolitis, intestinal obstruction and intestinal bacteriological infections. Case presentation We report the case of a 12-month-old boy who died of pneumatosis coli caused by an acute intestinal gas gangrene after prolonged artificial alimentation. Conclusion While intestinal gas gangrene is a highly uncommon cause of pneumatosis coli, it is important to consider it as a differential diagnosis, especially in patients receiving a prolonged artificial food supply. These patients may develop intestinal gas gangrene due to a dysfunctional intestinal barrier. PMID:18652650

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

PubMed Central

la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

2013-01-01

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen

PubMed Central

Bellanova, G.; Valduga, P.; Costa, A.; Barbareschi, M.; De Carli, N.; Giannelli, G.; Di Sipio, A.; Prezzi, C.; Ciarleglio, F.A.; Beltempo, P.; Marcucci, S.; Giacomin, D.; Depretis, G.; Brolese, A.

2015-01-01

Introduction Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. Materials and methods A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel’s diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2 mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. Discussion The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. Conclusion Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery. PMID:26188982

Liver grafts from selected older donors do not have significantly more ischaemia reperfusion injury

PubMed Central

Martins, Paulo N; Chang, Sue; Mahadevapa, Basant; Martins, Ann-Britt; Sheiner, Patricia

2011-01-01

Background There is a general concern that aged organs are more susceptible to ischaemia. In the light of recent proposals to change the liver allocation system by expanding regional sharing, it is feared that increased cold ischaemia time of grafts from older donors may reduce graft survival. The aim of this study was to correlate donor age and the patterns of ischaemia reperfusion injury and synthetic function early after liver transplantation. Methods We performed a retrospective study of first transplants using a single-centre electronic database. Patterns of liver injury (based on transaminases and post-reperfusion biopsy), synthetic function (international normalized ratio [INR]), and graft and patient survival in recipients receiving liver grafts from donors aged ≥65 years (group 1, n= 50) were compared with equivalent patterns in a matched cohort of recipients transplanted with grafts from donors aged <65 years (group 2, n= 50). Results There was no significant difference in transaminase levels from day 0 to day 6 after transplantation. When groups 1 and 2 were subdivided into two subgroups based on the duration of graft cold ischaemia time (<8 h and ≥8 h), there was no statistical difference in transaminase levels during the first 7 days. There were two cases (4%) of primary non-function in group 1 and one (2%) in group 2. Initial poor function did not differ significantly between the groups (26% vs. 24%; P= 0.81). In addition, there was no difference in histological changes in post-reperfusion biopsies (21% vs. 34%; P= 0.078) and rate of acute rejection episodes in the first year (30% vs. 32%; P= 0.99). There was no significant difference between groups 1 and 2 in 1-year patient and graft survivals (78% vs. 90% [P= 0.17]; 88% vs. 94% [P= 0.48], respectively). Conclusions Judiciously selected livers from aged donors are not associated with major increased susceptibility to ischaemia reperfusion injury. PMID:21309940

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury.

PubMed

Gupta, Ram; Singh, Manjeet; Sharma, Ajay

2003-08-01

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Zero-ischaemia robotic partial nephrectomy (RPN) for hilar tumours.

PubMed

Abreu, André L C; Gill, Inderbir S; Desai, Mihir M

2011-09-01

• Robotic partial nephrectomy (RPN) has emerged as an attractive minimally invasive nephron-sparing surgical option. However, on-going concerns about RPN include: (i) prolonged ischaemia time with potential implications on renal functional outcomes, and (ii) questions about the ability of RPN to address technically challenging hilar tumours. • Herein, we detail the technique and present initial perioperative outcomes of our novel technique of zero-ischaemia RPN for complex hilar tumours. • Since May 2010, >100 patients underwent minimally invasive zero-ischaemia PN. Of these, 21 had procedure done robotically. Of these, seven patients had hilar tumours. RPN was offered to all patients irrespective of tumour or reno-vascular anatomy, contralateral kidney characteristics or renal function. • Data were prospectively collected and recorded in an Institutional Review Board-approved database. • We detail our zero-ischaemia RPN technique and present early perioperative outcomes. • Zero-ischaemia RPN was successful in all cases without any hilar clamping. The median (range) tumour size was 4.1 (2.6-6.4) cm and the median RENAL score was 10 (8-10). • The warm ischaemia time was zero in all cases. • The median (range) operative time was 222 (150-330) min, estimated blood loss was 150 (100-500) mL, and the percentage kidney spared was 75 (50-90)%. The median hospital stay was 4 (3-6) days. • There were no intraoperative complications; two patients had postoperative complications (Clavien grade I and II). No patient had a postoperative haemorrhage, urological/renal complication or lost a kidney. All tumour specimens had negative surgical margins on pathology. • The median absolute decrease in serum creatinine and estimated glomerular filtration rate at discharge was 0 (0.2-0.7) mg/dL (P = 0.4) and 5 (-16 to 29) mL/min per 1.73 m(2) (P = 0.8), respectively. • Zero-ischaemia RPN for hilar tumours is safe and feasible and to our knowledge the first report in

Possible mechanism of acute effect of ethanol on intestinal IgA expression in rat.

PubMed

Budec, Mirela; Koko, Vesna; Todorović, Vera; Marković, Dragana; Postić, Marija; Drndarević, Neda; Spasić, Andelka; Mitrović, Olivera

2007-06-01

The purpose of this study was to investigate the possible mechanism of acute effect of ethanol on IgA expression in rat intestine. To this end, adult female Wistar rats showing diestrus day 1 were treated with (a) ethanol (2 or 4 g/kg, i.p.); (b) N omega-nitro-L-arginine-methyl ester (L-NAME), which inhibits the activity of all isoforms of nitric oxide synthase, (30 mg/kg, s.c.) followed by ethanol 3 h later; and (c) L-NAME (30 mg/kg, s.c.) followed by saline 3 h later. Saline-injected and untreated rats were used as controls. The animals were sacrificed 0.5 h after ethanol administration. Intestinal expression of IgA was evaluated by both immunohistochemistry and Western immunoblotting. Morphometric analysis showed that acute ethanol treatment increased the number of IgA-immunoreactive cells in a dose-dependent manner. Pretreatment with L-NAME abolished this action of alcohol. Injection of L-NAME followed by saline had no influence on the number of IgA+cells. The results, obtained by Western immunoblotting, paralleled our immunohistochemical findings. Taken together, these data suggest that acute effect of ethanol on intestinal IgA might be mediated by endogenous nitric oxide.

Monitoring of glycolytic activity secondary to ischaemia in knee replacement surgery.

PubMed

León-Muñoz, V J; Lisón-Almagro, A J; Hernández-García, C H; López-López, M

2018-04-17

To non-invasively assess tissue lesion secondary to ischaemia applied during knee replacement surgery. Secondary objectives: to assess whether this lesion correlates with the duration of ischaemia and whether instrumental and gender variables influence it. Prospective cohort study. Pre and postoperative serum lactate levels have been determined as an indicator of glycolytic activity secondary to ischaemia in 88 patients. Serum lactate determination was performed by reactive strips of enzymatic-amperometric detection on capillary blood. Preoperative serum lactate levels (mean and SD): 2.467±1.036 mmol/L. Postoperative serum lactate levels: 3.938±2.018 mmol/L. Ischaemia time 102.98±18.25minutes. Postoperative serum lactate levels were significantly higher than preoperative lactate levels. There are no statistical differences according to the time that the ischaemia was prolonged, gender or type of instrumentation used. In our study, postoperative serum lactate values were significantly higher than preoperative lactate values, with no correlation to the duration of ischaemia during knee replacement surgery. Copyright © 2018 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Acute peri-operative beta blockade in intermediate-risk patients.

PubMed

Biccard, B M; Sear, J W; Foëx, P

2006-10-01

Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

PubMed

Eckstein, F S; Scheule, A M; Vogel, U; Schmid, S T; Miller, S; Jurmann, M J; Ziemer, G

1999-05-01

Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet's disease.

PubMed

Park, Jihye; Cheon, Jae Hee; Park, Yong Eun; Lee, Yoon Jee; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho

2017-05-01

Intestinal Behçet's disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal. We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients. Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding. The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058-4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084-24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070-9.462, p = 0.037). Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

PubMed

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

The impact of a focused vascular lower limb arterial duplex (F-VLAD) scan in management decisions for acute limb ischaemia.

PubMed

Normahani, Pasha; Aslam, Mohammed; Standfield, Nigel J; Jaffer, Usman

2017-01-01

To establish the diagnostic accuracy of a 'focused vascular lower limb arterial duplex scan (F-VLAD)' developed to facilitate rapid decision-making for acute limb ischaemia (ALI). Ten cases of ALI were identified from our patient database; clinical details, history and examination findings were extracted from the clinical notes. Original 'full' duplex ultrasound (DUS) pictorial reports were 're-formatted' to include only anatomical segments included in the 'F-VLAD' scan. The series of 10 reports were emailed to 1741 vascular surgeons. Each recipient received a random mixture of full and F-VLAD scans. Participants were asked regarding next step in management and confidence in decision-making (Likert scale; 1 strongly disagree, 5 strongly agree). The cases were again sent out to the same database and respondents were asked as to the cause of ischaemia (embolic or thrombosis). Eighty-one participants responded to the first survey and 43 participants to the second survey. Participants felt more confident making decisions regarding management using the full duplex report compared to the F-VLAD report (4 (3-4) vs 3 (2-4), median (IQR); p<0.001). However, there was no significant difference in diagnostic accuracy (differentiating embolus from thrombosis) when comparing the F-VLAD and full DUS reports (85.4% vs 88.3%; p=0.461). F-VLAD and 'full' DUS reports had comparable sensitivity (85.1% vs 86.8%), specificity (85.6% vs 89.2%),positive predictive value (PPV) (80.4% vs 81.9%) and negative predictive value (NPV) (89.2% vs 92.2%), respectively. The F-VLAD scan has comparable accuracy to a traditional full DUS in diagnosing the underlying aetiology of ALI. This may facilitate surgeon-performed point-of-care DUS.

Immunomicrobiological monitoring of orovaccinal therapy in acute intestinal infections.

PubMed

Corridori, S; Negretti, F

1983-01-01

A double blind study in 42 patients (treated and controls) affected by acute uncomplicated salmonellosis was performed. The treatment consisted of an oral inactivated tetravaccine at the dose of 1 ampoule twice a day for 15 consecutive days. Microbiological and serological techniques (determination of intestinal secretory IgA by means of immunofluorescence, titration of copro and serum antibodies, quali-quantitative coprocultures) have shown that the administration of oral vaccine improved both the clinical and the immunomicrobiological picture in treated patients.

Malrotation with transverse colon volvulus in early pregnancy: a rare cause for acute intestinal obstruction

PubMed Central

Sharma, Digvijoy; Parameshwaran, Rajesh; Dani, Tushar; Shetty, Prashanth

2013-01-01

Colonic volvulus is a relatively uncommon cause of large bowel obstruction, accounting for 10% of colonic obstructions. Volvulus of the transverse colon is quite rare, accounting for only 4–11% of all reported cases. We report an unusual case of documented volvulus of the transverse colon in a pregnant woman with intestinal malrotation and concomitant acute intestinal obstruction by congenital bands and adhesions. PMID:23964051

Crisis management during anaesthesia: myocardial ischaemia and infarction.

PubMed

Ludbrook, G L; Webb, R K; Currie, M; Watterson, L M

2005-06-01

Myocardial ischaemia and infarction are significant perioperative complications which are associated with poor patient outcome. Anaesthetic practice should therefore focus, particularly in the at risk patient, on their prevention, their accurate detection, on the identification of precipitating factors, and on rapid effective management. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK" supplemented by a specific sub-algorithm for myocardial ischaemia and infarction in the management of myocardial ischaemia and/or infarction occurring in association with anaesthesia. The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. Of the 125 incidents retrieved from the 4000 reports, 40 (1%) were considered to demonstrate myocardial infarction or ischaemia. The use of the structured approach described in this paper would have led to appropriate management in 90% of cases, with the remaining 10% requiring other sub-algorithms. It was considered that the application of this structured approach would have led to earlier recognition and/or better management of the problem in 45% of cases. Close and continuous monitoring of patients at risk of myocardial ischaemia during anaesthesia is necessary, using optimal ECG lead configurations, but sensitivity of this monitoring is not 100%. Coronary vasodilatation with glyceryl trinitrate (GTN) should not be withheld when indicated and the early use of beta blocking drugs should be considered even with normal blood pressures and heart rates.

Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawakami, Kentaro; Minami, Naoki; Matsuura, Minoru

Background and aims: Acute graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation, which often targets gastrointestinal (GI) tract. Osteopontin (OPN) plays an important physiological role in the efficient development of Th1 immune responses and cell survival by inhibiting apoptosis. The role of OPN in acute GI-GVHD is poorly understood. In the present study, we investigated the role of OPN in donor T cells in the pathogenicity of acute GI-GVHD. Methods: OPN knockout (KO) mice and C57BL/6 (B6) mice were used as donors, and (C57BL/6 × DBA/2) F1 (BDF1) mice were used as allograft recipients. Mice with acutemore » GI-GVHD were divided into three groups: the control group (BDF1→BDF1), B6 group (B6→BDF1), and OPN-KO group (OPN-KO→BDF1). Bone marrow cells and spleen cells from donors were transplanted to lethally irradiated recipients. Clinical GVHD scores were assessed daily. Recipients were euthanized on day 7 after transplantation, and colons and small intestines were collected for various analyses. Results: The clinical GVHD score in the OPN-KO group was significantly increased compared with the B6 and control groups. We observed a difference in the severity of colonic GVHD between the OPN-KO group and B6 group, but not small intestinal-GVHD between these groups. Interferon-γ, Tumor necrosis factor-α, Interleukin-17A, and Interleukin-18 gene expression in the OPN-KO group was differed between the colon and small intestine. Flow cytometric analysis revealed that the fluorescence intensity of splenic and colonic CD8 T cells expressing Fas Ligand was increased in the OPN-KO group compared with the B6 group. Conclusion: We demonstrated that the importance of OPN in T cells in the onset of acute GI-GVHD involves regulating apoptosis of the intestinal cell via the Fas-Fas Ligand pathway. - Highlights: • A lack of osteopontin in donor cells exacerbated clinical gastrointestinal GVHD. • Donor cells

Multi-detector CT features of acute intestinal ischemia and their prognostic correlations.

PubMed

Moschetta, Marco; Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

2014-05-28

Acute intestinal ischemia is an abdominal emergency occurring in nearly 1% of patients presenting with acute abdomen. The causes can be occlusive or non occlusive. Early diagnosis is important to improve survival rates. In most cases of late or missed diagnosis, the mortality rate from intestinal infarction is very high, with a reported value ranging from 60% to 90%. Multi-detector computed tomography (MDCT) is a fundamental imaging technique that must be promptly performed in all patients with suspected bowel ischemia. Thanks to the new dedicated reconstruction program, its diagnostic potential is much improved compared to the past and currently it is superior to that of any other noninvasive technique. The increased spatial and temporal resolution, high-quality multi-planar reconstructions, maximum intensity projections, vessel probe, surface-shaded volume rending and tissue transition projections make MDCT the gold standard for the diagnosis of intestinal ischemia, with reported sensitivity, specificity, positive and negative predictive values of 64%-93%, 92%-100%, 90%-100% and 94%-98%, respectively. MDCT contributes to appropriate treatment planning and provides important prognostic information thanks to its ability to define the nature and extent of the disease. The purpose of this review is to examine the diagnostic and prognostic role of MDCT in bowel ischemia with special regard to the state of art new reconstruction software.

Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

PubMed Central

Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Squadrito, Mario Leonardo; Finisguerra, Veronica; Deschoemaeker, Sofie; Bruyére, Françoise; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Magat, Julie; Bhattacharyya, Tapan; Anisimov, Andrey; Jordan, Benedicte F.; Alitalo, Kari; Maxwell, Patrick; Gallez, Bernard; Zhuang, Zhen W.; Saito, Yoshihiko; Simons, Michael; De Palma, Michele; Mazzone, Massimiliano

2015-01-01

PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage1–5. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion6–8. We show that Phd2 (also known as Egln1) haplodeficient (Phd2+/−) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2+/− mice was due to an expansion of tissue-resident, M2-like macrophages9,10 and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a proarteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2+/− macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders. PMID:21983962

Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease.

PubMed

Ameh, Emmanuel A; Ayeni, Michael A; Kache, Stephen A; Mshelbwala, Philip M

2013-01-01

Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease) is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. A retrospective review of 52 children with acute intestinal disease who had enterostomy as a damage control measure in 12 years. There were 34 (65.4%) boys and 18 (34.6%) girls aged 3 days-13 years (median 9 months), comprising 27 (51.9%) neonates and infants and 25 (48.1%) older children. The primary indication for enterostomy in neonates and infants was intestinal gangrene 25 (92.6%) and perforated typhoid ileitis 22 (88%) in older children. Enterostomy was performed as the initial surgery in 33 (63.5%) patients and as a salvage procedure following anastomotic dehiscence in 19 (36.5%) patients. Enterostomy-related complications occurred in 19 (36.5%) patients, including 11 (21.2%) patients with skin excoriations and eight (15.4%) with hypokalaemia. There were four (7.7%) deaths (aged 19 days, 3 months, 3½ years and 10 years, respectively) directly related to the enterostomy, from hypokalaemia at 4, 12, 20 and 28 days postoperatively, respectively. Twenty other patients died shortly after surgery from their primary disease. Twenty of 28 surviving patients have had their enterostomy closed without complications, while eight are awaiting enterostomy closure. Damage-control enterostomy is useful in management of severely ill children with intestinal perforation or gangrene. Careful and meticulous attention to fluid and electrolyte balance, and stoma care, especially in the first several days following surgery, are important in preventing morbidity and mortality.

Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

PubMed

Guzel, Ahmet; Kanter, Mehmet; Guzel, Aygul; Pergel, Ahmet; Erboga, Mustafa

2012-06-01

The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

Neutrophil-derived JAML Inhibits Repair of Intestinal Epithelial Injury During Acute Inflammation

PubMed Central

Weber, Dominique A.; Sumagin, Ronen; McCall, Ingrid C.; Leoni, Giovanna; Neumann, Philipp A.; Andargachew, Rakieb; Brazil, Jennifer C.; Medina-Contreras, Oscar; Denning, Timothy L.; Nusrat, Asma; Parkos, Charles A.

2014-01-01

Neutrophil transepithelial migration (TEM) during acute inflammation is associated with mucosal injury. Using models of acute mucosal injury in-vitro and in-vivo, we describe a new mechanism by which neutrophils infiltrating the intestinal mucosa disrupt epithelial homeostasis. We report that junctional adhesion molecule-like protein (JAML) is cleaved from neutrophil surface by zinc-metalloproteases during TEM. Neutrophil-derived soluble JAML bound to the epithelial tight junction protein coxsackie-adenovirus receptor (CAR) resulting in compromised barrier and inhibition of wound repair, through decreased epithelial proliferation. The deleterious effects of JAML on barrier and wound repair were reversed with an anti-JAML mAb that inhibits JAML-CAR binding. Thus, JAML released from transmigrating neutrophils across inflamed epithelia can promote recruitment of leukocytes and aid in clearance of invading microorganisms. However, sustained release of JAML under pathologic conditions associated with persistence of large numbers of infiltrated neutrophil would compromise intestinal barrier and inhibit mucosal healing. Targeting JAML-CAR interactions may thus improve mucosal healing responses under conditions of dysregulated neutrophil recruitment. PMID:24621992

Comparison of the effects of isobutylmethylxanthine and milrinone on ischaemia-induced arrhythmias and platelet aggregation in anaesthetized rabbits.

PubMed Central

Holbrook, M.; Coker, S. J.

1989-01-01

1. The aim of this study was to compare the effects of the non-selective phosphodiesterase (PDE) inhibitor, isobutylmethylxanthine (IBMX) and the selective PDE III inhibitor, milrinone, in a rabbit model of acute myocardial ischaemia. 2. Coronary artery occlusion caused changes in the ST-segment of the ECG and ectopic activity in all control rabbits. Ventricular fibrillation occurred in 10 out of 14 (71%) of these animals. Pretreatment with IBMX 100 micrograms kg-1 plus 10 micrograms kg-1 min-1, starting 10 min before coronary artery occlusion, reduced ischaemia-induced ST-segment changes and ventricular fibrillation occurred in only 10% of this group (n = 10). A similar dose of milrinone had no antiarrhythmic activity, whereas with a lower dose of milrinone, 30 micrograms kg-1 plus 3 micrograms kg-1 min-1 (n = 10), only 30% of rabbits fibrillated and ST-segment changes were attenuated. 3. Acute administration of both IBMX and milrinone reduced arterial blood pressure. With the higher dose of milrinone a significant effect was still present after 10 min of drug infusion. A greater hypotensive response to the higher dose of milrinone was observed in the rabbits which subsequently fibrillated during ischaemia. A marked tachycardia was also observed after administration of the higher dose of milrinone. 4. At the end of the experiment platelet aggregation was studied ex vivo. ADP-induced aggregation was reduced by pretreatment of the rabbits with milrinone but not IBMX. Both PDE inhibitors enhanced the ability of isoprenaline to inhibit ADP-induced platelet aggregation but milrinone was more effective, particularly at the higher dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2478245

Methotrexate causes acute hyperplasia of enterochromaffin cells containing substance P in the intestinal mucosa of rats.

PubMed

Machida, Takuji; Takano, Yuho; Iizuka, Kenji; Machida, Maiko; Hirafuji, Masahiko

2017-03-01

This study aimed to investigate the acute and chronic effect of methotrexate on the intestinal substance P metabolism after a single administration to rats. Methotrexate caused a significant increase in the number of substance P-containing cells in the ileal mucosa both at 24 and 96 h. Most of enterochromaffin cells expressing l-tryptophan hydroxylase contained substance P. The expression of Tac1 mRNA was increased by methotrexate at 24 h, but not at 96 h. Thus, methotrexate causes acute hyperplasia of enterochromaffin cells in the intestinal mucosa of rats with a transient increase in the production of substance P. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

L-Arginyl-3,4-Spermidine is neuroprotective in several in vitro models of neurodegeneration and in vivo ischaemia without suppressing synaptic transmission

PubMed Central

Morrison, Barclay; Pringle, Ashley K; McManus, Terence; Ellard, John; Bradley, Mark; Signorelli, Francesco; Iannotti, Fausto; Sundstrom, Lars E

2002-01-01

Stroke is the third most common cause of death in the world, and there is a clear need to develop new therapeutics for the stroke victim. To address this need, we generated a combinatorial library of polyamine compounds based on sFTX-3.3 toxin from which L-Arginyl-3,4-Spermidine (L-Arg-3,4) emerged as a lead neuroprotective compound. In the present study, we have extended earlier results to examine the compound's neuroprotective actions in greater detail. In an in vitro ischaemia model, L-Arg-3,4 significantly reduced CA1 cell death when administered prior to induction of 60 min of ischaemia as well as when administered immediately after ischaemia. Surprisingly, L-Arg-3,4 continued to prevent cell death significantly when administration was delayed for as long as 60 min after ischaemia. L-Arg-3,4 significantly reduced cell death in excitotoxicity models mediated by glutamate, NMDA, AMPA, or kainate. Unlike glutamate receptor antagonists, 300 μM L-Arg-3,4 did not suppress synaptic transmission as measured by evoked responses in acute hippocampal slices. L-Arg-3,4 provided significant protection, in vitro, in a superoxide mediated injury model and prevented an increase of superoxide production after AMPA or NMDA stimulation. It also decreased nitric oxide production after in vitro ischaemia and NMDA stimulation, but did so without inhibiting nitric oxide synthase directly. Furthermore, L-Arg-3,4 was significantly neuroprotective in an in vivo model of global forebrain ischaemia, without any apparent neurological side-effects. Taken together, these results demonstrate that L-Arg-3,4 is protective in several models of neurodegeneration and may have potential as a new therapeutic compound for the treatment of stroke, trauma, and other neurodegenerative diseases. PMID:12466235

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

PubMed

Morawiec, Beata; Fournier, Stephane; Tapponnier, Maxime; Prior, John O; Monney, Pierre; Dunet, Vincent; Lauriers, Nathalie; Recordon, Frederique; Trana, Catalina; Iglesias, Juan-Fernando; Kawecki, Damian; Boulat, Olivier; Bardy, Daniel; Lamsidri, Sabine; Eeckhout, Eric; Hugli, Olivier; Muller, Olivier

2017-07-10

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

Jinhong Tablet Reduces Damage of Intestinal Mucosal Barrier in Rats with Acute Biliary Infection via Bcl-2/Bax mRNA and Protein Regulation

PubMed Central

Wang, YongQi; Xie, Jinkun; Zhang, Xuelin; Gu, Honggang

2017-01-01

Objective To explore the effects and mechanism of Jinhong Tablet on intestinal mucosal barrier function and SIRS in rats with acute biliary infection. Methods 36 SD male rats were divided into three groups: sham operation (control), acute biliary infection (ABI) model, and Jinhong Tablet (Jinhong) group. Jinhong group were force-fed with Jinhong Tablet, while the other two groups received oral saline. At days 3 and 5, morphological changes of intestinal mucosa were assessed. Serum diamine oxidase (DAO), D-lactate, and endotoxin levels were measured. And the genes bcl-2 and bax in intestinal tissues were tested by real-time PCR and Western blotting. Results Intestinal damage was significantly less severe in Jinhong group compared with ABI group, as indicated by Chiu's scoring, TUNEL analysis, and serum DAO, D-lactic acid, and endotoxin levels. Additionally, the expression of bax mRNA and protein was decreased and the ratio of bcl-2/bax mRNA and protein was increased compared with ABI group. Conclusion Jinhong Tablet had a positive intervention on acute biliary infection through improving inflammation and intestinal mucosal barrier, inhibiting excessive apoptosis of intestinal epithelial cells via bax and bcl-2 gene, and protein regulation. PMID:29234407

Ischaemia-reperfusion injury in central retinal artery occlusion.

PubMed

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-10-21

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90.

Effect of ischaemia on somatosensory evoked potentials in diabetic patients.

PubMed Central

López-Alburquerque, T; García Miguel, A; Ruiz Ezquerro, J J; de Portugal Alvarez, J

1987-01-01

The nerve action potential at the elbow and somatosensory evoked potentials (SEPs) at the scalp were recorded over 30 minutes of tourniquet-induced limb ischaemia in 10 diabetic patients and 10 controls. According to the SEP changes, an increased resistance to nerve ischaemia in diabetic patients was observed. The pathways involved in SEP conduction are discussed. PMID:3585354

Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.

PubMed

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-10-27

Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

PubMed Central

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-01-01

Background Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. Methods The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Results Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. Conclusion We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT. PMID:25321166

Endoglin regulates renal ischaemia-reperfusion injury.

PubMed

Docherty, Neil G; López-Novoa, José M; Arevalo, Miguel; Düwel, Annette; Rodriguez-Peña, Ana; Pérez-Barriocanal, Fernando; Bernabeu, Carmelo; Eleno, Nélida

2006-08-01

Renal ischaemia-reperfusion (I-R) can cause acute tubular necrosis and chronic renal deterioration. Endoglin, an accessory receptor for Transforming Growth Factor-beta1 (TGF-beta1), is expressed on activated endothelium during macrophage maturation and implicated in the control of fibrosis, angiogenesis and inflammation. Endoglin expression was monitored over 14 days after renal I-R in rats. As endoglin-null mice are not viable, the role of endoglin in I-R was studied by comparing renal I-R injury in haploinsufficient mice (Eng(+/-)) and their wild-type littermates (Eng(+/+)). Renal function, morphology and molecular markers of acute renal injury and inflammation were compared. Endoglin mRNA up-regulation in the post-ischaemic kidneys of rats occurred at 12 h after I-R; endoglin protein levels were elevated throughout the study period. Expression was initially localized to the vascular endothelium, then extended to fibrotic and inflamed areas of the interstitium. Two days after I-R, plasma creatinine elevation and acute tubular necrosis were less marked in Eng(+/-) than in Eng(+/+) mice. Significant up-regulation of endoglin protein was found only in the post-ischaemic kidneys of Eng(+/+) mice and coincided with an increased mRNA expression of the TGF-beta1 and collagen IV (alpha1) chain genes. Significant increases in vascular cell adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase (iNOS) expression, nitrosative stress, myeloperoxidase activity and CD68 staining for macrophages were evident in post-ischaemic kidneys of Eng(+/+), but not Eng(+/-) mice, suggesting that impaired endothelial activation and macrophage maturation may account for the reduced injury in post-ischaemic kidneys of Eng(+/-) mice. Endoglin is up-regulated in the post-ischaemic kidney and endoglin-haploinsufficient mice are protected from renal I-R injury. Endoglin may play a primary role in promoting inflammatory responses following renal I-R.

Ischaemia-reperfusion injury in central retinal artery occlusion

PubMed Central

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-01-01

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90. PMID:24145508

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis.

PubMed

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 micromol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1alpha), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3beta at serine 9 (p-GSK-3beta), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1alpha, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway.

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis

PubMed Central

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 μmol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1α), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3β at serine 9 (p-GSK-3β), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1α, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway. PMID:19602048

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema.

PubMed

Wessel, Matthew M; Nair, Nandini; Aaker, Grant D; Ehrlich, Joshua R; D'Amico, Donald J; Kiss, Szilárd

2012-05-01

To determine the relationship between retinal ischaemia and the presence of macular oedema (DMO) in patients with diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWFA) imaging. A retrospective review of 122 eyes of 70 treatment-naïve diabetic patients who underwent diagnostic UWFA using the Optos 200Tx imaging system. Two independent, masked graders quantified the area of retinal ischaemia. Based on clinical examination and optical coherence tomography (OCT), each patient was given a binary classification as either having DMO or no DMO. McNemar's test (with Yates' correction as indicated) and a two-sample test of proportions were used to determine the relationship between DMO and ischaemia for binary and proportional data, respectively. Linear and logistic models were constructed using generalised estimating equations to test relationships between independent variables, covariates and outcomes while controlling for inter-eye correlation, age, gender, haemoglobin A1c, mean arterial pressure and dependence on insulin. Seventy-six eyes (62%) exhibited areas of retinal ischaemia. There was a significant direct correlation between DMO and peripheral retinal ischaemia as seen on UWFA (p<0.001). In addition, patients with retinal ischaemia had 3.75 times increased odds of having DMO compared with those without retinal ischaemia (CI 1.26 to 11.13, p<0.02). Retinal ischaemia is significantly correlated with DMO in treatment-naïve patients with DR. UWFA is a useful tool for detecting peripheral retinal ischaemia, which may have direct implications in the diagnosis, follow-up and treatment such as targeted peripheral photocoagulation.

Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema

PubMed Central

Wessel, Matthew M; Nair, Nandini; Aaker, Grant D; Ehrlich, Joshua R; D'Amico, Donald J

2012-01-01

Purpose To determine the relationship between retinal ischaemia and the presence of macular oedema (DMO) in patients with diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWFA) imaging. Methods A retrospective review of 122 eyes of 70 treatment-naïve diabetic patients who underwent diagnostic UWFA using the Optos 200Tx imaging system. Two independent, masked graders quantified the area of retinal ischaemia. Based on clinical examination and optical coherence tomography (OCT), each patient was given a binary classification as either having DMO or no DMO. McNemar's test (with Yates' correction as indicated) and a two-sample test of proportions were used to determine the relationship between DMO and ischaemia for binary and proportional data, respectively. Linear and logistic models were constructed using generalised estimating equations to test relationships between independent variables, covariates and outcomes while controlling for inter-eye correlation, age, gender, haemoglobin A1c, mean arterial pressure and dependence on insulin. Results Seventy-six eyes (62%) exhibited areas of retinal ischaemia. There was a significant direct correlation between DMO and peripheral retinal ischaemia as seen on UWFA (p<0.001). In addition, patients with retinal ischaemia had 3.75 times increased odds of having DMO compared with those without retinal ischaemia (CI 1.26 to 11.13, p<0.02). Conclusion Retinal ischaemia is significantly correlated with DMO in treatment-naïve patients with DR. UWFA is a useful tool for detecting peripheral retinal ischaemia, which may have direct implications in the diagnosis, follow-up and treatment such as targeted peripheral photocoagulation. PMID:22423055

The threatened stomach: management of the acute gastric volvulus.

PubMed

Light, D; Links, D; Griffin, M

2016-05-01

Acute presentation of gastric volvulus is a rare condition with a high mortality for acute ischaemia. This study was undertaken to investigate the acute management, diagnosis, and long-term outcomes of patients presenting with acute gastric volvulus. Cases were reviewed retrospectively from 2004 to 2014. Patients presenting as an emergency admission with acute gastric volvulus were included. Thirty-six patients were included, five of whom had previous surgery. The mean age was 71 years old. All patients presented with vomiting and chest/epigastric pain. CT was diagnostic in all 26 patients. Barium swallow was diagnostic in two/four patients. OGD was diagnostic in 9 of 20 patients. All patients had an NG tube placed, and eight patients were treated conservatively and made a full recovery. Twenty-nine patients proceeded to surgery. Nine had a laparoscopic repair with two open conversions. Four patients had gastric necrosis, and all had open surgery with resection. Three patients had a mediastinal perforation, and one patient required an additional thoracotomy. All patients with viable stomach had a hiatal repair (where appropriate), 11 had a gastropexy, and 11 had a fundoplication. Mortality for gastric necrosis/perforation was 30 %. Mean postoperative stay was 4 days for laparoscopic repair and 8 days for uncomplicated open surgery. Nine of twenty-nine had transient dysphagia postoperatively. Three of eight patients treated conservatively had an elective procedure subsequently. Acute paraoesophageal hiatus hernia requires early resuscitation and diagnosis. CT should be favoured in assessment, and an NG tube placed promptly. A conservative management may be considered safely in stable patients. Surgical management should be prompt for unstable patients. Gastric ischaemia or perforation has a mortality of 30 %. Laparoscopic repair has a shorter postoperative stay, but has a higher recurrence rate. Surgery for patients without gastric ischaemia has good long

Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.

PubMed

Jeukendrup, A E; Vet-Joop, K; Sturk, A; Stegen, J H; Senden, J; Saris, W H; Wagenmakers, A J

2000-01-01

The aim of the present study was to establish whether gastro-intestinal (GI) complaints observed during and after ultra-endurance exercise are related to gut ischaemia-associated leakage of endotoxins [lipopolysaccharide (LPS)] into the circulation and associated cytokine production. Therefore we collected blood samples from 29 athletes before, immediately after, and 1, 2 and 16 h after a long-distance triathlon for measurement of LPS, tumour necrosis factor-alpha and interleukin-6 (IL-6). As the cytokine response would trigger an acute-phase response, characteristic variables of these responses were also measured, along with creatine kinase (CK) to obtain an indicator of muscle damage. There was a high incidence (93% of all participants) of GI symptoms; 45% reported severe complaints and 7% of the participants abandoned the race because of severe GI distress. Mild endotoxaemia (5-15 pg/ml) was evident in 68% of the athletes immediately after the race, as also indicated by a reduction in IgG anti-LPS levels. In addition, we observed production of IL-6 (27-fold increase immediately after the race), leading to an acute-phase response (20-fold increase in C-reactive protein and 12% decrease in pre-albumin 16 h after the race). The extent of endotoxaemia was not correlated with the GI complaints or the IL-6 response, but did show a correlation with the elevation in C-reactive protein (r(s) 0.389; P=0.037). Creatine kinase levels were increased significantly immediately post-race, and increased further in the follow-up period. Creatine kinase levels did not correlate with those of either IL-6 or C-reactive protein. It is therefore concluded that LPS does enter the circulation after ultra-endurance exercise and may, together with muscle damage, be responsible for the increased cytokine response and hence GI complaints in these athletes.

Intestinal Pseudo-Obstruction

MedlinePlus

... condition as adults. Intestinal pseudo-obstruction may be acute, occurring suddenly and lasting a short time, or it may be chronic, or long lasting. Acute colonic pseudo-obstruction, also called Ogilvie syndrome or ...

Endocannabinoids protect the rat isolated heart against ischaemia

PubMed Central

Lépicier, Philippe; Bouchard, Jean-François; Lagneux, Caroline; Lamontagne, Daniel

2003-01-01

The purpose of this study was to determine whether endocannabinoids can protect the heart against ischaemia and reperfusion. Rat isolated hearts were exposed to low-flow ischaemia (0.5–0.6 ml min−1) and reperfusion. Functional recovery as well as CK and LDH overflow into the coronary effluent were monitored. Infarct size was determined at the end of the experiments. Phosphorylation levels of p38, ERK1/2, and JNK/SAPK kinases were measured by Western blots. None of the untreated hearts recovered from ischaemia during the reperfusion period. Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2-arachidonoylglycerol (2-AG), but not anandamide (up to 1 μM), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH. PEA and 2-AG also reduced infarct size. The CB2-receptor antagonist, SR144528, blocked completely the cardioprotective effect of both PEA and 2-AG, whereas the CB1-receptor antagonist, SR141716A, blocked partially the effect of 2-AG only. In contrast, both ACEA and JWH015, two selective agonists for CB1- and CB2- receptors, respectively, reduced infarct size at a concentration of 50 nM. PEA enhanced the phosphorylation level of p38 MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580, and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC inhibitor, chelerythrine. In conclusion, endocannabinoids exert a strong cardioprotective effect in a rat model of ischaemia–reperfusion that is mediated mainly through CB2-receptors, and involves p38, ERK1/2, as well as PKC activation. PMID:12813004

Dai-Huang-Fu-Zi-Tang Alleviates Intestinal Injury Associated with Severe Acute Pancreatitis by Regulating Mitochondrial Permeability Transition Pore of Intestinal Mucosa Epithelial Cells

PubMed Central

Kang, Xin; Liang, Zhengkai; Zhan, Libin; Song, Jianbo; Wang, Yi; Yang, Yilun; Fan, Zhiwei; Bai, Lizhi

2017-01-01

Objective The aim of the present study was to examine whether Dai-Huang-Fu-Zi-Tang (DHFZT) could regulate mitochondrial permeability transition pore (MPTP) of intestinal mucosa epithelial cells for alleviating intestinal injury associated with severe acute pancreatitis (SAP). Methods A total of 72 Sprague-Dawley rats were randomly divided into 3 groups (sham group, SAP group, and DHFZT group, n = 24 per group). The rats in each group were divided into 4 subgroups (n = 6 per subgroup) accordingly at 1, 3, 6, and 12 h after the operation. The contents of serum amylase, D-lactic acid, diamine oxidase activity, and degree of MPTP were measured by dry chemical method and enzyme-linked immunosorbent assay. The change of mitochondria of intestinal epithelial cells was observed by transmission electron microscopy. Results The present study showed that DHFZT inhibited the openness of MPTP at 3, 6, and 12 h after the operation. Meanwhile, it reduced the contents of serum D-lactic acid and activity of diamine oxidase activity and also drastically relieved histopathological manifestations and epithelial cells injury of intestine. Conclusion DHFZT alleviates intestinal injury associated SAP via reducing the openness of MPTP. In addition, DHFZT could also decrease the content of serum diamine oxidase activity and D-lactic acid after SAP. PMID:29403537

The detection of brain ischaemia in rats by inductive phase shift spectroscopy.

PubMed

González, C A; Villanueva, C; Vera, C; Flores, O; Reyes, R D; Rubinsky, B

2009-08-01

Ischaemia in the brain is an important clinical problem that is often monitored and studied with expensive devices such as MRI and PET, which are not readily available in low economical resource parts of the world. We have developed a new less expensive tool for non-invasive monitoring of ischaemia in the brain. This is a first feasibility study describing the concept. The system is based on the hypothesis that electromagnetic properties of the tissue change during ischaemia and that measuring the electromagnetic properties of the bulk of the brain with non-contact means can detect these changes. The apparatus we have built and whose design we describe here consists of two electromagnetic coils placed around the head. The system measures the bulk change in time of the phase difference between the electromagnetic signal on the two coils in a range of frequencies. A mathematical model simulating the device and the measurement is also introduced. Ischaemia was induced in the brain of rats by occlusion of the right cerebral and carotid arteries. Experimental subjects were monitored for 24 h. Inductive phase shift measurements were made at five frequencies in the range of 0.1-50 MHz eight times during the observation period. An ex vivo estimation of the percentage of necrosis in the ischemic subjects at t = 24 h was done. The mathematical model was also applied to the experimental tested situation. The results of both experiments and theory show significant phase shifts increase as a function of frequency and ischaemia time. The theoretical and experimental results suggest that the tested technique has the potential to detect the processes and level of ischaemia in the brain by non-invasive, continuous, bulk volumetric monitoring with a simple and inexpensive apparatus.

Effects of nicergoline on rabbit electroretinogram during recovery after ischaemia in light and dark.

PubMed

Blasco, G; Traversa, U; Drago, F

1997-11-01

Nicergoline is an ergot alkaloid derivative acting as a neuroprotective agent. In the present investigation, b-wave time-course recovery profiles under both light- and dark-adapted conditions, were studied in order to evaluate the possible effectiveness of nicergoline in the protection of the rabbit retina. Retinal ischaemia was induced by bilateral occlusion of common carotid artery in male rabbit of the Dutch strain. Groups of animals were subjected to 15-, 30- and 60-min periods of ischaemia under pentobarbital anaesthesia. Electroretinogram recordings were simultaneously obtained from both eyes, using, as the stimulus, the brightest flash from a stimulator positioned 15 cm in front of each eye. The treatment with nicergoline, administered immediately before the carotid occlusion, induced a significant protection only when the ischaemia seemed to cause retinal damage that the reperfusion alone was not able to recover completely. Nicergoline did not modify the recovery rate after 15-min or 30-min light-adapted and 15-min dark-adapted ischaemia; in these conditions the controls showed a full recovery. After 30-min dark-adapted ischaemia, the maximum recovery of the controls was 82%, and nicergoline significantly improved b-wave amplitude at all time points of reperfusion up to the complete recovery. Rabbit retina was irreversibly damaged by a 60-min ischaemia. In these conditions nicergoline significantly increased the percentage of b-wave recovery both in light- and dark-adapted ERG. Nicergoline, probably on the basis of its metabolic actions, seems to be effective in severe conditions of hypoxia and is more potent in dark than in light-adapted conditions. Its effectiveness in these experimental conditions could be justified by the different oxygen consumption of the photoreceptors in light and dark and the different sensitivity of cones and rods to the ischaemia.

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

PubMed Central

Xiong, Yuxia; Chen, Li; Fan, Ling; Wang, Lulu; Zhou, Yejiang; Qin, Dalian; Sun, Qin; Wu, Jianming; Cao, Shousong

2018-01-01

Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

PubMed Central

van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

2015-01-01

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death.

PubMed

Tak, Eunyoung; Park, Gil-Chun; Kim, Seok-Hwan; Jun, Dae Young; Lee, Jooyoung; Hwang, Shin; Song, Gi-Won; Lee, Sung-Gyu

2016-12-01

Objective To investigate the protective effects of epigallocatechin-3-gallate (EGCG), a major polyphenol source in green tea, against hepatic ischaemia-reperfusion injury in mice. Methods The partial hepatic ischaemia-reperfusion injury model was created by employing the hanging-weight method in C57BL/6 male mice. EGCG (50 mg/kg) was administered via an intraperitoneal injection 45 min before performing the reperfusion. A number of markers of inflammation, oxidative stress, apoptosis and liver injury were measured after the ischaemia-reperfusion injury had been induced. Results The treatment groups were: sham-operated (Sham, n = 10), hepatic ischaemia-reperfusion injury (IR, n = 10), and EGCG with ischaemia-reperfusion injury (EGCG-treated IR, n = 10). Hepatic ischaemia-reperfusion injury increased the levels of biochemical and histological markers of liver injury, increased the levels of malondialdehyde, reduced the glutathione/oxidized glutathione ratio, increased the levels of oxidative stress and lipid peroxidation markers, decreased B-cell lymphoma 2 levels, and increased the levels of Bax, cytochrome c, cleaved caspase-3, and cleaved caspase-9. Pretreatment with EGCG ameliorated all of these changes. Conclusion The antioxidant and antiapoptotic effects of EGCG protected against hepatic ischaemia-reperfusion injury in mice.

A childhood-onset intestinal toxemia botulism during chemotherapy for relapsed acute leukemia.

PubMed

Ohyama, Noriko; Torio, Michiko; Nakashima, Kentaro; Koga, Yuuki; Kanno, Shunsuke; Nishio, Hisanori; Nishiyama, Kei; Sasazuki, Momoko; Kato, Haru; Asakura, Hiroshi; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Sakai, Yasunari; Ohga, Shouichi

2017-09-18

Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.

Abdominal symptoms during physical exercise and the role of gastrointestinal ischaemia: a study in 12 symptomatic athletes.

PubMed

ter Steege, Rinze W F; Geelkerken, Robert H; Huisman, Ad B; Kolkman, Jeroen J

2012-10-01

Gastrointestinal (GI) symptoms during exercise may be caused by GI ischaemia. The authors report their experience with the diagnostic protocol and management of athletes with symptomatic exercise-induced GI ischaemia. The value of prolonged exercise tonometry in the diagnostic protocol of these patients was evaluated. Patients referred for GI symptoms during physical exercise underwent a standardised diagnostic protocol, including prolonged exercise tonometry. Indicators of GI ischaemia, as measured by tonometry, were related to the presence of symptoms during the exercise test (S+ and S- tests) and exercise intensity. 12 athletes were specifically referred for GI symptoms during exercise (five males and seven females; median age 29 years (range 15-46 years)). Type of sport was cycling, long-distance running and triathlon. Median duration of symptoms was 32 months (range 7-240 months). Splanchnic artery stenosis was found in one athlete. GI ischaemia was found in six athletes during submaximal exercise. All athletes had gastric and jejunal ischaemia during maximum intensity exercise. No significant difference was found in gastric and jejunal Pco(2) or gradients between S+ and S- tests during any phase of the exercise protocol. In S+ tests, but not in S- tests, a significant correlation between lactate and gastric gradient was found. In S+ tests, the regression coefficients of gradients were higher than those in S- tests. Treatment advice aimed at limiting GI ischaemia were successful in reducing complaints in the majority of the athletes. GI ischaemia was present in all athletes during maximum intensity exercise and in 50% during submaximal exercise. Athletes with GI symptoms had higher gastric gradients per mmol/l increase in lactate, suggesting an increased susceptibility for the development of ischaemia during exercise. Treatment advice aimed at limiting GI ischaemia helped the majority of the referred athletes to reduce their complaints. Our results suggest an

[PULMONARY AND INTESTINAL TUBERCULOSIS DEVELOPING ACUTE TUBERCULOUS PERFORATION OF THE INTESTINE DURING ANTITUBERCULOSIS THERAPY].

PubMed

Saitou, Miwako; Suzuki, Tomoko; Niitsuma, Katsunao

2015-09-01

Intestinal tuberculosis (TB) was recognized as the most common complication with a high frequency of active pulmonary TB during the TB epidemic period. However, intestinal TB has become a rare disease, and intestinal perforation due to intestinal TB is extremely rare. We herein report two cases of tuberculous intestinal perforation. A 41-year-old man was admitted to our hospital complaining of persistent cough and anorexia. He was in poor nutritional condition, and his body mass index (BMI) and prognostic nutrition index (PNI) were 13.4 and 36.4, respectively. He was diagnosed with pulmonary TB and received anti-TB therapy. On the 51st day of hospitalization, he developed intestinal perforation. Pathologically caseating epithelioid granulomas were noted at the ulcer lesion. A 61-year-old man was admitted to our hospital due to miliary TB caused by intestinal TB. He had taken oral immunosuppressive drugs and steroids for dermatomyositis over the previous eight years and had a poor nutritional condition, with a BMI of 13.4 and a PNI of 14.4. While receiving anti-TB therapy, he developed intestinal perforation on the 97th day of hospitalization. The patient's poor nutritional condition and immune reconstitution may have contributed to the intestinal perforation.

Intestinal Fatty Acid Binding Protein and Citrulline as Markers of Gut Injury and Prognosis in Patients With Acute Pancreatitis.

PubMed

Goswami, Pooja; Sonika, Ujjwal; Moka, Praneeth; Sreenivas, Vishnubhatla; Saraya, Anoop

Severe acute pancreatitis (AP) is associated with high mortality due to systemic inflammatory response syndrome in the early phase and secondary infection in the later phase. Concomitant intestinal ischemia often results in gut injury. We studied intestinal fatty acid binding protein (IFABP) and citrulline levels as markers of gut injury to predict prognosis in AP. Acute pancreatitis patients at admission and controls were studied. Serum IFABP was measured by enzyme-linked immunosorbent assay and plasma citrulline by high-performance liquid chromatography technique. Ultrastructural changes in duodenal biopsy were also compared between the 2 groups. The IFABP concentration was significantly higher in AP cases (n = 94) compared with controls (n = 100) (mean [standard deviation], 592.5 [753.6] vs 87.8 [67.6] pg/mL; P < 0.001) and in patients with severe AP versus mild AP (738.3 [955.3] vs 404.0 [263.3] pg/ mL, P = 0.03). Citrulline concentration was lower in AP versus controls (29.9 [33.8] vs 83.9 [60.1] μg/L, P < 0.001). We propose a model by which these biomarkers (IFABP >350 pg/mL and citrulline <18 μg/L) are able to predict poor prognosis in 33.9% of patients with AP. The gut injury was also validated via ultrastructural changes. Intestinal fatty acid binding protein is a promising prognostic marker in acute pancreatitis.

Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke.

PubMed

Kanazawa, Masato; Kawamura, Kunio; Takahashi, Tetsuya; Miura, Minami; Tanaka, Yoshinori; Koyama, Misaki; Toriyabe, Masafumi; Igarashi, Hironaka; Nakada, Tsutomu; Nishihara, Masugi; Nishizawa, Masatoyo; Shimohata, Takayoshi

2015-07-01

In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption

Silent myocardial ischaemia: the Tan Tock Seng experience.

PubMed

Mak, K H; Tan, E K; Chew, L; Gan, S H; Chan, A L

1991-10-01

The results of treadmill exercise stress test (TMX) for ischaemia is based on ST-segment depression. Patients with positive test may or may not be symptomatic. This study examines if there are any differences between these two groups of patients. A total of thirty-nine patients with coronary artery disease and positive TMX results in 1988 was studied. There were 16 patients with chest pain and 23 without. They were followed-up for a mean period of 16.9 and 15.2 months respectively. The following factors were found not to be statistically significant between these two groups of patients: age, sex, race, height, weight, history of hypertension, diabetes mellitus or smoking, indication for the test, use of drugs, total and HDL-cholesterol, exercise duration and the initial double product. The difference between the maximal double product of the two groups was statistically significant (p = 0.004). In the follow-up period, in the group of patients with silent myocardial ischaemia, one had a cardiac event and one underwent revascularisation. While in the symptomatic group, two had cardiac events and seven underwent revascularisation. There were no deaths in either group. The difference in overall outcome was significant statistically (p = 0.002). Therefore, patients with silent myocardial ischaemia have a higher maximal double product in TMX; hence a higher maximal workload and a less adverse outcome compared to symptomatic patients.

Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

PubMed

Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

2015-05-01

The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

Curcumin modulates free radical quenching in myocardial ischaemia in rats.

PubMed

Manikandan, Panchatcharam; Sumitra, Miriyala; Aishwarya, Srinivasan; Manohar, Bhakthavatsalam Murali; Lokanadam, Beema; Puvanakrishnan, Rengarajulu

2004-10-01

This study was designed to investigate the protective effect of curcumin (CUR) against isoprenaline induced myocardial ischaemia in rat myocardium. The effect of single oral dose of curcumin (15 mg kg(-1)), administered 30 min before and/or after the onset of ischaemia, was investigated by assessing oxidative stress related biochemical parameters in rat myocardium. Curcumin pre and post-treatment (PPT) was shown to decrease the levels of xanthine oxidase, superoxide anion, lipid peroxides (LPs) and myeloperoxidase while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities were significantly increased after curcumin PPT. Histopathological and transmission electron microscopical studies also confirmed the severe myocardial damage occurring as a consequence of isoprenaline induced ischaemia and they also showed the significant improvement effected by curcumin PPT. These findings provided evidence that curcumin was found to protect rat myocardium against ischaemic insult and the protective effect could be attributed to its antioxidant properties as well as its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant superoxide anion production.

"Metabolically healthy" obesity: Prevalence, clinical features and association with myocardial ischaemia.

PubMed

De Lorenzo, Andrea; Glerian, Leticia; Amaral, Ana Carolina; Reis, Thiago B; Lima, Ronaldo S L

To evaluate the prevalence of the "metabolically healthy" (MH) or "metabolically unhealthy" (MU) obesity phenotypes and their association with cardiorespiratory fitness and inducible myocardial ischaemia. Individuals without known coronary artery disease undergoing myocardial perfusion single-photon emission computed tomography (MPS) were studied. Those without dyslipidemia, hypertension, or diabetes were considered MH, and when ≥1 of these was present, MU status was considered present. Summed stress and difference perfusion scores (SSS and SDS, respectively) were calculated; a SDS >1 defined ischaemic MPS. MH patients were 35.0% of the nonobese population and 23.5% of the obese (p<0.001). The prevalence of ischaemia was not significantly different between MH patients with obesity or MH patients without obesity (10.9% vs 9.1%, p=0.3), except for patients with body mass index ≥40kg/m 2 (21.9%). MH obese patients were less frequently able to exercise and had lower exercise capacity than the nonobese patients. The prevalence of myocardial ischaemia was not significantly different between MH obese or nonobese individuals, supporting the concept of the "metabolically healthy obesity". However, there are other factors involved, such as the ability to exercise, that influence the risk of myocardial ischaemia, limiting the "safety" of that obesity phenotype. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Intestinal lymphangiectasia in children

PubMed Central

Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.

2016-01-01

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404

An integrative review of health-related quality of life in patients with critical limb ischaemia.

PubMed

Monaro, Susan; West, Sandra; Gullick, Janice

2017-10-01

To examine the domains and the domain-specific characteristics within a peripheral arterial disease health-related quality of life framework for their usefulness in defining critical limb ischaemia health-related quality of life. Critical Limb Ischaemia presents a highly individualised set of personal and health circumstances. Treatment options include conservative management, revascularisation or amputation. However, the links between treatment decisions and quality of life require further investigation. The framework for this integrative review was the peripheral arterial disease-specific health-related quality of life domains identified by Treat-Jacobson et al. The literature expanded and refined Treat-Jacobson's framework by modifying the characteristics to better describe health-related quality of life in critical limb ischaemia. Given that critical limb ischaemia is a highly individualised situation with powerful health-related quality of life implications, further research focusing on patient and family-centred decision-making relating to therapeutic options and advanced care planning is required. A critical limb ischaemia-specific, health-related quality of life tool is required to capture both the unique characteristics of this disorder, and the outcomes for active or conservative care among this complex group of patients. © 2016 John Wiley & Sons Ltd.

Measurement of intestinal edema using an impedance analyzer circuit.

PubMed

Radhakrishnan, Ravi S; Shah, Kunal; Xue, Hasen; Moore-Olufemi, Stacey D; Moore, Frederick A; Weisbrodt, Norman W; Allen, Steven J; Gill, Brijesh; Cox, Charles S

2007-03-01

Acute intestinal edema adversely affects intestinal transit, permeability, and contractility. Current resuscitation modalities, while effective, are associated with development of acute intestinal edema. Knowledge of levels of tissue edema would allow clinicians to monitor intestinal tissue water and may help prevent the detrimental effects of edema. However, there is no simple method to measure intestinal tissue water without biopsy. We sought to develop a tissue impedance analyzer to measure tissue edema, without the need for invasive biopsy. Oscillating voltage input was applied to the analyzer circuit and an oscilloscope measured the voltage output across any load. Rats were randomized to three groups: sham, mild edema (80 mL/kg of NS resuscitation), and severe edema (80 mL/kg of NS resuscitation with intestinal venous hypertension). Intestinal edema was measured by wet-to-dry tissue weight ratio. Bowel impedance was measured and converted to capacitance using a standard curve. Acute intestinal edema causes a significant increase in bowel capacitance. This capacitance can be used to predict tissue water concentration. Using an impedance analyzer circuit, it is possible to measure intestinal edema reliably and quickly. This may prove to be a useful tool in the resuscitation of critically ill patients.

Colonic casts: unexpected complications of colonic ischaemia.

PubMed

Mantas, D; Damaskos, C; Bamias, G; Dimitroulis, D

2016-09-01

Introduction Extensive colonic ischaemia can result in passage of a colonic 'cast' (CC) through the rectum. Case Study We report a 69-year-old male who initially underwent surgery to remove a sessile polyp. On postoperative day (POD)15, he was febrile, suffering from diarrhoea, and was treated conservatively. On POD18, the patient returned to our hospital with a CC that presented after defaecation. Computed tomography of the abdomen revealed a CC extending from the descending colon to the anal orifice with presentation of air between the affected colonic wall and the CC. The patient was treated conservatively and discharged on POD20 without complications having passed the CC (≈80cm) completely and becoming afebrile. Conclusions In most cases, the cause of CC passage is surgery for colorectal cancer or repair of an abdominal aortic aneurysm. A mild-to-severe presentation is dependent upon the bowel-wall layers affected by ischaemia and which therefore are included in the CC.

Honey improves spermatogenesis and hormone secretion in testicular ischaemia-reperfusion-induced injury in rats.

PubMed

Gholami, M; Abbaszadeh, A; Khanipour Khayat, Z; Anbari, K; Baharvand, P; Gharravi, A M

2018-02-01

This study was conducted to survey the protective effect of pre-treatment with Persian honey during post-ischaemia reperfusion on ischaemia-reperfusion (IR)-induced testis injury. Animals were divided into four groups of IR, honey + ischaemia- reperfusion (HIR), vitamin C + ischaemia- reperfusion (VIR) and carbohydrates + ischaemia- reperfusion (CIR). The testes were examined for spermatogenesis index. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed. Total serum concentration of FSH, LH and testosterone was measured using ELISA. All data were expressed as mean ± SD in each group, and significance was set at p ≤ .05. Spermatogenesis index was significant in the HIR group (p < .001). Serum levels of FSH and LH were significantly higher in the CIR and HIR groups. Serum levels of testosterone were significantly higher in VIR and HIR groups. Apoptotic cells in IR and CIR groups increased significantly statistically (p < .001), while in HIR and VIR groups, the number of apoptotic cells decreased and the positive cells of TUNEL staining were detected in spermatocytes and spermatid. The present study indicates that honey decreases the cellular damage and apoptosis during testicular I/R injury, with significant protective effects on reproductive hormone production. © 2017 Blackwell Verlag GmbH.

Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice.

PubMed

Yu, Yi; Feng, Xiaoyan; Vieten, Gertrud; Dippel, Stephanie; Imvised, Tawan; Gueler, Faikah; Ure, Benno M; Kuebler, Jochen F; Klemann, Christian

2017-01-01

Ischemia-reperfusion injury (IRI) is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αβ T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αβ T cells play in IRI to the gut. Adult wild-type (WT) and αβ T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI. Intestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αβ T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αβ T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable. An increasing body of evidence demonstrates that αβ T cells play a key role in IRI. In the gut, however, αβ T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αβ T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion.

PubMed

Schütte, H; Löckinger, A; Seeger, W; Grimminger, F

2001-07-01

High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus 0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22, 1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI2 and SNP and no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.

Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National Institute for Cardiovascular Outcomes Research (NICOR).

PubMed

Simms, Alexander D; Reynolds, Stephanie; Pieper, Karen; Baxter, Paul D; Cattle, Brian A; Batin, Phillip D; Wilson, John I; Deanfield, John E; West, Robert M; Fox, Keith A A; Hall, Alistair S; Gale, Christopher P

2013-01-01

To evaluate the performance of the National Institute for Health and Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE) (MG) and adjusted mini-GRACE (AMG) risk scores. Retrospective observational study. 215 acute hospitals in England and Wales. 137 084 patients discharged from hospital with a diagnosis of acute myocardial infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia National Audit Project (MINAP). Model performance indices of calibration accuracy, discriminative and explanatory performance, including net reclassification index (NRI) and integrated discrimination improvement. Of 495 263 index patients hospitalised with AMI, there were 53 196 ST elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test: p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients with NSTEMI, chronic heart failure, chronic renal failure and in patients aged ≥85 years. The AMG and MG risk scores, utilised by NICE, demonstrated good performance across a range of indices using MINAP data, but performed less well in higher risk subgroups. Although indices were better for AMG, its application may be constrained by missing predictors.

Circulating intestinal fatty acid-binding protein (I-FABP) levels in acute decompensated heart failure.

PubMed

Kitai, Takeshi; Kim, Yong-Hyun; Kiefer, Kathryn; Morales, Rommel; Borowski, Allen G; Grodin, Justin L; Tang, W H Wilson

2017-06-01

Venous congestion has become increasingly recognized as a potential contributor to end-organ dysfunction in heart failure. Elevated I-FABP, which is excreted specifically from damaged intestinal epithelial cells, has been found in patients with abdominal hypertension and intestinal ischemia. We hypothesize that elevated intestinal fatty acid-binding protein (I-FABP) levels would identify patients with more advanced heart failure who have venous and intestinal congestion. Baseline serum I-FABP levels were measured in 69 acute decompensated heart failure (ADHF) patients admitted to the intensive care unit for invasive hemodynamic monitoring and tailored medical therapy. Comprehensive echocardiography examinations were performed in all study patients, and clinical outcomes (death, cardiac transplant or left ventricular assist device placement) were assessed. The median circulating I-FABP level was 853pg/ml (interquartile range: 533 to 1448pg/ml). Age, gender, race, and baseline comorbidities were comparable between patients with low and high I-FABP levels. Although there were no significant correlations between I-FABP levels and invasively-measured hemodynamic parameters nor echocardiographic parameters, patients with higher I-FABP levels (≥853g/ml) had significantly worse clinical outcomes compared to those with lower I-FABP levels (<853pg/ml, P=0.025). Circulating I-FABP levels had no association with invasively-measured hemodynamic parameters, but were associated with adverse clinical outcomes in patients with ADHF with systolic dysfunction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia

PubMed Central

Ruozi, Giulia; Bortolotti, Francesca; Falcione, Antonella; Dal Ferro, Matteo; Ukovich, Laura; Macedo, Antero; Zentilin, Lorena; Filigheddu, Nicoletta; Cappellari, Gianluca Gortan; Baldini, Giovanna; Zweyer, Marina; Barazzoni, Rocco; Graziani, Andrea; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Functional screening of expression libraries in vivo would offer the possibility of identifying novel biotherapeutics without a priori knowledge of their biochemical function. Here we describe a procedure for the functional selection of tissue-protective factors based on the in vivo delivery of arrayed cDNA libraries from the mouse secretome using adeno-associated virus (AAV) vectors. Application of this technique, which we call FunSel, in the context of acute ischaemia, revealed that the peptide ghrelin protects skeletal muscle and heart from ischaemic damage. When delivered to the heart using an AAV9 vector, ghrelin markedly reduces infarct size and preserves cardiac function over time. This protective activity associates with the capacity of ghrelin to sustain autophagy and remove dysfunctional mitochondria after myocardial infarction. Our findings describe an innovative tool to identify biological therapeutics and reveal a novel role of ghrelin as an inducer of myoprotective autophagy. PMID:26066847

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

PubMed Central

Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

2015-01-01

Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity

Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability.

PubMed

Willumsen, J F; Darling, J C; Kitundu, J A; Kingamkono, R R; Msengi, A E; Mduma, B; Sullivan, K R; Tomkins, A M

1997-03-01

There is a strong relationship between diarrhoea, malnutrition, and intestinal integrity. To investigate the effect of different dietary-treatment on intestinal permeability during acute diarrhoea, 87 Tanzanian children aged 6-25 months were recruited to this study when admitted to hospital. Children with acute diarrhoea were rehydrated and then randomly assigned to one of three dietary treatment groups: a conventional low-energy density porridge, a high-energy density amylase digested porridge (AMD), or a high-energy density amylase digested and then fermented porridge (FAD). Lactulose/mannitol permeability tests were performed on admission, at 3 days, and at follow-up 2 and 4 weeks after discharge. The lactulose/mannitol (L/M) ratios were compared between dietary treatment groups and to a group of age-matched, healthy control subjects. Children with diarrhoea had higher L/M ratios (geometric mean 0.85, 95% CI 0.68-1.05) compared with control subjects (0.14, 0.12-0.17) on admission. There was a significant difference in the change in L/M ratio between admission and 3 days between dietary treatment groups in favour of the FAD group (p < 0.05). Dietary treatment and intestinal damage at admission explain 13.5% of the variation in L/M ratio, but when age at admission and age at weaning are included as covariants, 21.9% is explained. FAD porridge seems to be more effective in the treatment of intestinal permeability than AMD or conventional porridge. Urinary lactose concentrations in spot urine samples taken prior to the permeability test were also measured. There was a significant correlation with the L/M ratio (correlation coefficient = 0.62, p < 0.001).

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability.

PubMed

Lamers, F P L; van Dijkman, P R M; Kuijpers, Th J A; van Herpen, G

2003-02-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

PubMed Central

Lamers, F.P.L.; van Dijkman, P.R.M.; Kuijpers, Th.J.A.; van Herpen, G.

2003-01-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was

Bilirubin provides perforator flap protection from ischaemia-reperfusion injury in a rat model: a preliminary result.

PubMed

Kim, Sung Young; Rah, Dong Kyun; Chong, Yosep; Lee, Song Hyun; Park, Tae Hwan

2016-10-01

The use of bilirubin, a well-known and powerful antioxidant, has gained popularity in recent years because of its role in the prevention of ischaemic heart disease in patients with Gilbert's syndrome. We investigate the effects of bilirubin on ischaemia-reperfusion (I/R) injury using a rat perforator flap model. Forty-eight rats were randomly divided into two groups: experimental (bilirubin) group (n = 24) and control group (n = 24). In each group, elevated bilateral deep inferior epigastric perforator (DIEP) flaps were created. The right (no ischaemia side) and left (ischaemia side) DIEP flaps were separated according to the presence of ischaemia induction. Ischaemia was induced in anaesthetised rats by perforator clamping for 15 or 30 minutes. After surgery, the flap survival was assessed daily on postoperative days 0 to 5, and overall histological changes of DIEP flaps above the perforator were analysed at postoperative day 5. The flap survival rate in the bilirubin group was significantly higher than that in the control group at the ischaemia side following perforator clamping for 15 or 30 minutes (93·42 ± 4·48% versus 89·63 ± 3·98%, P = 0·002; and 83·96 ± 4·23% versus 36·46 ± 6·38%, P < 0·001, respectively). The difference in flap survival between the two groups was the most prominent on the ischaemic side following 30 minutes of perforator clamping. From a morphologic perspective, pre-treatment with bilirubin was found to alleviate perforator flap necrosis caused by I/R injury in this experimental rat model. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

PubMed

Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

1996-09-01

To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

PubMed

Spray, S; Johansson, S E; Radziwon-Balicka, A; Haanes, K A; Warfvinge, K; Povlsen, G K; Kelly, P A T; Edvinsson, L

2017-08-01

Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. © 2016 Scandinavian Physiological Society. Published by John Wiley

The prognostic role of stress echocardiography in a contemporary population and the clinical significance of limited apical ischaemia.

PubMed

Papachristidis, Alexandros; Roper, Damian; Cassar Demarco, Daniela; Tsironis, Ioannis; Papitsas, Michael; Byrne, Jonathan; Alfakih, Khaled; Monaghan, Mark J

2016-12-01

In this study, we aim to reassess the prognostic value of stress echocardiography (SE) in a contemporary population and to evaluate the clinical significance of limited apical ischaemia, which has not been previously studied. We included 880 patients who underwent SE. Follow-up data with regards to MACCE (cardiac death, myocardial infarction, any repeat revascularisation and cerebrovascular accident) were collected over 12 months after the SE. Mortality data were recorded over 27.02 ± 4.6 months (5.5-34.2 months). We sought to investigate the predictors of MACCE and all-cause mortality. In a multivariable analysis, only the positive result of SE was predictive of MACCE (HR, 3.71; P = 0.012). The positive SE group was divided into 2 subgroups: (a) inducible ischaemia limited to the apical segments ('apical ischaemia') and (b) ischaemia in any other segments with or without apical involvement ('other positive'). The subgroup of patients with apical ischaemia had a significantly worse outcome compared to the patients with a negative SE (HR, 3.68; P = 0.041) but a similar outcome to the 'other positive' subgroup. However, when investigated with invasive coronary angiography, the prevalence of coronary artery disease (CAD) and their rate of revascularisation was considerably lower. Only age (HR, 1.07; P < 0.001) was correlated with all-cause mortality. SE remains a strong predictor of patients' outcome in a contemporary population. A positive SE result was the only predictor of 12-month MACCE. The subgroup of patients with limited apical ischaemia have similar outcome to patients with ischaemia in other segments despite a lower prevalence of CAD and a lower revascularisation rate. © 2016 The authors.

Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

PubMed Central

Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2008-01-01

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38

[THE MODES OF EVALUATION OF TYPE OF DEHYDRATION IN CHILDREN HOSPITALIZED BECAUSE OF ACUTE INTESTINAL INFECTION].

PubMed

Krieger, E A; Samodova, O V; Gulakova, N N; Aruiev, A B; Krylova, L A; Titova, L V

2015-11-01

Every year about 800,000 cases of intestinal infections end in lethal outcome due to dehydration. The different types of dehydration acquire differential approach to correction. Everywhere there is no application of routine detection of osmolarity of blood plasma under exicosis in children in view of absence of possibility of instrumental measurement. The search of techniques is needed to make it possible to indirectly detect types of dehydration in children hospitalized because of acute intestinal infection with purpose to apply rationale therapy of water-electrolyte disorders. The sampling of 32 patients with intestinal infections accompanied with signs of exicosis degree I-III was examined. The detection of osmolarity of blood was implemented by instrumental technique using gas analyzer ABL 800 Flex (Radiometer; Denmark) and five estimate techniques according to results of biochemical analysis of blood. The differences in precision of measurement of osmolarity of blood plasma by instrumental and estimate techniques were compared using Bland-Altman graphic technique. It is established that formula: 2x[Na+kp] + [glucosekp] (mmol/l) is the most recise. Its application provided results comparable with values detected by instrumental mode.

Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus1

PubMed Central

Frenguelli, Bruno G; Wigmore, Geoffrey; Llaudet, Enrique; Dale, Nicholas

2007-01-01

Abstract Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pre-treament with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain. PMID:17459147

Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias

PubMed Central

Ng, Fu Siong; Shadi, Iqbal T.; Peters, Nicholas S.; Lyon, Alexander R.

2013-01-01

Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8 min followed by 10 min of reperfusion: (1) Control n = 10; (2) 1 μM of ivabradine perfusion n = 10; (3) 1 μM of ivabradine + 5 Hz atrial pacing throughout ischaemia–reperfusion n = 5; (4) 1 μM of ivabradine + 5 Hz pacing only at reperfusion; (5) 100 μM of ivabradine was used as a 1 ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n = 5; 5 Hz pacing n = 5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195 ± 11 bpm vs. control 272 ± 14 bpm, p < 0.05) and at reperfusion (168 ± 13 bpm vs. 276 ± 14 bpm, p < 0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p < 0.05). Pacing throughout ischaemia–reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2 ± 1.3 min vs. 5.1 ± 0.7 min, p < 0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7 ± 4.3 min vs. 14.5 ± 0.6 min, p < 0.05). Ivabradine administered throughout ischaemia

Mechanical Intestinal Obstruction in a Porcine Model: Effects of Intra-Abdominal Hypertension. A Preliminary Study

PubMed Central

Sánchez-Margallo, F. M.; Latorre, R.; López-Albors, O.; Wise, R.; Malbrain, M. L. N. G.; Castellanos, G.

2016-01-01

Introduction Mechanical intestinal obstruction is a disorder associated with intra-abdominal hypertension and abdominal compartment syndrome. As the large intestine intraluminal and intra-abdominal pressures are increased, so the patient’s risk for intestinal ischaemia. Previous studies have focused on hypoperfusion and bacterial translocation without considering the concomitant effect of intra-abdominal hypertension. The objective of this study was to design and evaluate a mechanical intestinal obstruction model in pigs similar to the human pathophysiology. Materials and Methods Fifteen pigs were divided into three groups: a control group (n = 5) and two groups of 5 pigs with intra-abdominal hypertension induced by mechanical intestinal obstruction. The intra-abdominal pressures of 20 mmHg were maintained for 2 and 5 hours respectively. Hemodynamic, respiratory and gastric intramucosal pH values, as well as blood tests were recorded every 30 min. Results Significant differences between the control and mechanical intestinal obstruction groups were noted. The mean arterial pressure, cardiac index, dynamic pulmonary compliance and abdominal perfusion pressure decreased. The systemic vascular resistance index, central venous pressure, pulse pressure variation, airway resistance and lactate increased within 2 hours from starting intra-abdominal hypertension (p<0.05). In addition, we observed increased values for the peak and plateau airway pressures, and low values of gastric intramucosal pH in the mechanical intestinal obstruction groups that were significant after 3 hours. Conclusion The mechanical intestinal obstruction model appears to adequately simulate the pathophysiology of intestinal obstruction that occurs in humans. Monitoring abdominal perfusion pressure, dynamic pulmonary compliance, gastric intramucosal pH and lactate values may provide insight in predicting the effects on endorgan function in patients with mechanical intestinal obstruction. PMID

Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences

PubMed Central

Purohit, Vishnudutt; Bode, J. Christian; Bode, Christiane; Brenner, David A.; Choudhry, Mashkoor A.; Hamilton, Frank; Kang, Y. James; Keshavarzian, Ali; Rao, Radhakrishna; Sartor, R. Balfour; Swanson, Christine; Turner, Jerrold R.

2008-01-01

This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram negative bacteria in the intestine which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, L-glutamine, oats supplementation, or zinc thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram negative bacteria and

Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.

PubMed

Yang, Yang; Qiu, Yuan; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Zhang, Chaojun; Yang, Hanwenbo; Teitelbaum, Daniel H; Sun, Li-Hua; Yang, Hua

2014-01-01

Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.

Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome.

PubMed

Thymann, Thomas; Stoll, Barbara; Mecklenburg, Lars; Burrin, Douglas G; Vegge, Andreas; Qvist, Niels; Eriksen, Thomas; Jeppesen, Palle B; Sangild, Per T

2014-06-01

Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model. Two-day-old pigs were subjected to resection of 50% of the small intestine (distal part), and the remnant intestine was exteriorized on the abdominal wall as a jejunostomy. All pigs were given total parenteral nutrition for 7 days and a single daily injection of the following doses of teduglutide: 0.01 (n = 6), 0.02 (n = 6), 0.1 (n = 5), or 0.2 mg · kg · day (n = 6), and compared with placebo (n = 9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (P < 0.05). There was a dose-dependent increase in weight per length of the remnant intestine (P < 0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (P < 0.001); however, functional and structural endpoints including activity of digestive enzymes, absorption of enteral nutrients, and immunohistochemistry (Ki67, villin, FABP2, ChgA, and GLP-2R) were not affected by the treatment. Teduglutide induces trophicity on the remnant intestine but has limited acute effects on functional endpoints. Significant effects of teduglutide on gut function may require a longer adaptation period and/or a more frequent administration of the peptide. In perspective, GLP-2 or its analogues may be relevant to improve intestinal adaptation in pediatric patients with short bowel syndrome.

Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters.

PubMed

Lee, C Y

2015-04-01

This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%. Exposure to both stress and HFD caused a further increase in corticosterone to 41%, while decreasing plasma adiponectin level. Restraint stress altered intestinal expression of SLC5A1, SLC2A2 and NPC1L1. These changes were enhanced in SHF rats. Adenosine was found to alleviate HFD-induced increase in glucose and insulin levels, suppress elevation of corticosterone in S rats and improve the altered nutrient transporters expression profiles. It also prevented upregulation of TNF-α in the intestine of SHF rats. In summary, a combination of stress and HFD exaggerated stress- and HFD-induced pathophysiological changes in the intestine, and biochemical parameters related to obesity. Adenosine attenuated the elevation of corticosterone and altered expression of SLC5A1, NPC1L1 and TNF-α. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Effects of Saccharomyces cerevisiae or boulardii yeasts on acute stress induced intestinal dysmotility.

PubMed

West, Christine; Stanisz, Andrew M; Wong, Annette; Kunze, Wolfgang A

2016-12-28

To investigate the capacity of Saccharomyces cerevisiae ( S. cerevisiae ) and Saccharomyces boulardii ( S. boulardii ) yeasts to reverse or to treat acute stress-related intestinal dysmotility. Adult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae , S. boulardii , or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls. S. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity

Effects of Saccharomyces cerevisiae or boulardii yeasts on acute stress induced intestinal dysmotility

PubMed Central

West, Christine; Stanisz, Andrew M; Wong, Annette; Kunze, Wolfgang A

2016-01-01

AIM To investigate the capacity of Saccharomyces cerevisiae (S. cerevisiae) and Saccharomyces boulardii (S. boulardii) yeasts to reverse or to treat acute stress-related intestinal dysmotility. METHODS Adult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae, S. boulardii, or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls. RESULTS S. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar

Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of oxidative stress and inflammation.

PubMed

Wang, Ming-Liang; Wei, Chun-Hua; Wang, Wen-Dong; Wang, Jia-Shun; Zhang, Jun; Wang, Jian-Jun

2018-05-01

Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of the left hilum for 1 h and subsequent reperfusion for 2 h. Histological scoring analysis showed that lung parenchymal damage was ameliorated in the melatonin pretreatment groups when compared with the IR group, with the IR + 20 mg/kg MT group showing the strongest effect among the melatonin pretreatment groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein expressions of inflammatory factors (tumour necrosis factor-α, interleukin-1β, NF-κB and IKK-γ) and apoptotic factors (cleaved caspase-3 and Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung injury scores in all groups. In contrast, the examination of superoxide dismutase showed a pattern contrary to that of the lung injury score in all groups. In addition, immunohistochemistry staining showed that the expressions of the antioxidants glutathione peroxidase and glutathione reductase were increased in the melatonin pretreatment groups. This study demonstrated that melatonin pretreatment attenuated lung ischaemia-reperfusion injury via inhibition of oxidative stress, inflammation and apoptosis.

Coronary responses to endothelin-1 and acetylcholine during partial coronary ischaemia and reperfusion in anaesthetized goats.

PubMed

Martínez, Maria Angeles; Fernández, Nuria; Monge, Luis; García-Villalón, Angel Luis; Sanz, Elena; Diéguez, Godofredo

2002-08-01

To examine coronary reactivity to acetylcholine and endothelin-1 (ET-1) during partial ischaemia and reperfusion, flow in the left circumflex coronary artery was measured electromagnetically, and coronary partial ischaemia was induced by stenosis of this artery in anaesthetized goats. In eight animals not treated with N(G)-nitro-l-arginine methyl ester (l-NAME), coronary stenosis reduced coronary flow by 45%, mean arterial pressure by 16% and coronary vascular conductance by 34%. During this ischaemia, coronary vasodilatation to acetylcholine (0.003-0.1 microg) and sodium nitroprusside (SNP; 1-10 microg) was markedly reduced, and coronary vasoconstriction to ET-1 (0.01-0.3 nmol) was attenuated. After 30 min of reperfusion, coronary flow, mean arterial pressure and coronary vascular conductance remained decreased, and the effects of acetylcholine, SNP and ET-1 were as in control animals. In six goats treated with N(G)-nitro-l-arginine methyl ester, coronary stenosis reduced coronary flow by 26% and coronary vascular conductance by 24%, but did not affect mean arterial pressure. During this ischaemia, coronary vasodilatation to acetylcholine and SNP was also markedly reduced, but vasoconstriction to ET-1 was unaffected. After 30 min of reperfusion, coronary flow and coronary vascular conductance remained decreased and mean arterial pressure was normal; in addition, the effects of acetylcholine were lower, those of SNP were similar and those of ET-1 were higher than in control animals. Therefore partial ischaemia reduces the coronary vasodilator reserve and blunts coronary vasoconstriction to ET-1, and reperfusion does not alter the endothelium-dependent and -independent coronary vasodilatation or vasoconstriction to ET-1.

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

Lymphangioma of the jejunal mesentery and jejunal polyps presenting as an acute abdomen in a teenager.

PubMed

Jayasundara, Jasb; Perera, E; Chandu de Silva, M V; Pathirana, A A

2017-03-01

Cystic lymphangioma of the small bowel mesentery is a rare clinical entity, especially after childhood. Medical literature reveals a limited number of such cases presenting as acute abdomen due to bowel obstruction, small bowel volvulus and bleeding into the tumour. We present the management experience of an 18-year-old woman who presented with rapid onset diffuse peritonism and raised inflammatory markers. Computed tomography showed a mass in the small bowel mesentery with suspicion of segmental bowel ischaemia. Emergency laparotomy revealed a mass in the mid-jejunal mesentery close to the bowel wall with no bowel ischaemia. The patient made an uncomplicated recovery after segmental bowel resection and end-to-end anastomosis. Histology confirmed the mass as a cystic lymphangioma involving the jejunal mesentery and two small jejunal polyps. Lymphangioma could be considered in the differential diagnosis of an acute abdomen in a young adult when the presentation is atypical.

The effects of S-nitrosoglutathione on intestinal ischemia reperfusion injury and acute lung injury in rats: Roles of oxidative stress and NF-κB.

PubMed

Turan, Inci; Sayan Ozacmak, Hale; Ozacmak, V Haktan; Barut, Figen; Ozacmak, I Diler

2018-06-01

Intestinal ischemia and reperfusion (I/R) induces oxidative stress, inflammatory response, and acute lung injury. S-nitrosoglutathione (GSNO), a nitric oxide donor, has been documented to have protective effects on experimental ischemia models. The aim of this study was to examine the effect of GSNO on I/R-induced intestine and lung damage and detect the potential mechanisms emphasizing the protective role of GSNO. Intestinal I/R was induced by occluding the superior mesenteric artery for 30 min followed by reperfusion for 180 min. GSNO was administered intravenously before reperfusion period (0.25 mg/kg). The levels of lipid peroxidation, reduced glutathione, and myeloperoxidase (MPO), histopathological evaluation and immunohistochemical expressions of both nuclear factor KappaB (NF-κB) and inducible nitric oxide (iNOS) in intestine and lung tissues were assessed. Histolopathologic evaluation demonstrated that intestinal I/R induced severe damages in the intestine and the lung tissues. Histopathological scores decreased with GSNO treatment. GSNO treatment reduced lipid peroxidation and MPO levels and inhibited expression of NF-κB and iNOS in the intestine. Our results suggest that GSNO treatment may ameliorate the intestinal and lung injury in rats, at least in part, by inhibiting inflammatory response and oxidative stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ostomy or intestinal anastomosis in cases of peritonitis.

PubMed

Rasslan, S; Margutti Fonoff, A; Soldá, S C; Angelo Casaroli, A

1995-01-01

Twenty-six patients showing peritonitis due to nontraumatic acute abdomen were submitted to ostomy. Mean age was 51 years (range 25-83), being 13 males and 13 females. Bowel obstruction (BO) was the most frequent cause of peritonitis (11 cases), followed by intestinal perforation (IP) (8 cases), acute mesenteric infarction (AMI) (5 cases), and acute abdomen of inflammatory/infectious origin (AAIO) (2 cases). Brook's ileostomy was performed on 65% of the patients. Jejunostomy was performed only in 4 patients, leading to a bad evolution. Overall mortality was 54%. Primary ostomy or anastomosis in cases of peritonitis constitute a highly controversial theme. Indications and problems involving the intestinal exteriorization in emergency surgery urgency are herein discussed.

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load.

PubMed

Vazquez, Bruna Perez; Vazquez, Thaís Perez; Miguel, Camila Botelho; Rodrigues, Wellington Francisco; Mendes, Maria Tays; de Oliveira, Carlo José Freire; Chica, Javier Emílio Lazo

2015-04-03

Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain. We used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 10(2)), medium (3 × 10(3)), and high (3 × 10(4)) parasite loads were generated by infecting C57BL/6 mice with "Y"-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey's multiple comparison post-test, Kruskal-Wallis test with Dunn's multiple comparison, χ2 test and Spearman correlation. High parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines. These experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

Effects of ischaemia upon reflex electromyographic responses evoked by stretch and vibration in human wrist flexor muscles.

PubMed Central

Cody, F W; Goodwin, C N; Richardson, H C

1987-01-01

1. The reflex electromyographic responses evoked in a wrist flexor muscle, flexor carpi radialis (f.c.r.), by forcible extension of the wrist ('stretch') and by vibration of the flexor tendon have been studied in normal subjects. Reflexes were elicited during the maintenance of a low level of voluntary flexor contraction (5% maximum). Stretch regularly produced a relatively prolonged (ca. 100 ms duration) increase in e.m.g. activity which was usually divisible into short-latency (ca. 25 ms, M1) and long-latency (ca. 50 ms, M2) peaks. Vibration produced a single, phasic peak, at short latency, with no sign of an accompanying long-latency wave comparable to the M2 stretch response. 2. Ischaemia was induced by inflation of a blood-pressure cuff around the upper arm and its effects upon the reflex patterns were studied. During ischaemia M1 stretch responses showed a more rapid and pronounced decline than did M2 responses and were abolished before voluntary power was appreciably affected. Vibration-evoked short-latency peaks changed in an essentially parallel manner to M1 stretch reflexes. During recovery from ischaemia M2 reflexes were restored before short-latency responses. 3. The patterns of reflex reductions in e.m.g. upon withdrawal of stimulation were also studied. Such troughs in activity, under non-ischaemic conditions, regularly commenced at short latency and were of relatively small amplitude. The records of several of the subjects, and particularly ones obtained during ischaemia, suggested that release of stretch (with concomitant stretch of antagonists) could elicit an additive, long-latency decline in e.m.g. The existence of any such separate, delayed component was never observed upon termination of vibration. 4. Measurements of changes in the latencies and durations of reflex components, accompanying the progression of ischaemia, indicated that depression of early reflex activity resulted in part from increases in the latencies of these initial peaks but

Lymphangiectasia of small intestine presenting as intussusception.

PubMed

Katoch, Pervez; Bhardwaj, Subhash

2008-01-01

Intussusception is defined as telescoping of a segment of gastrointestinal tract into an adjacent one. In small children, it is the commonest cause of intestinal obstruction. More than 90% of childhood intussusceptions are idiopathic. We report a rare case of localized small intestinal lymphangiectasia, presenting as intussusception in a 6-month-old male child. The child presented with features of acute intestinal obstruction for which he was later operated. The gross examination of excised ileocecal mass revealed intussusception. Histopathologic examination revealed lymphangiectasia of small intestine, which acted as a lead point for ileocecal intussusception. Postoperative period was uneventful.

Panoramic ECG display versus conventional ECG: ischaemia detection by critical care nurses.

PubMed

Wilson, Nick; Hassani, Aimen; Gibson, Vanessa; Lightfoot, Timothy; Zizzo, Claudio

2012-01-01

To compare accuracy and certainty of diagnosis of cardiac ischaemia using the Panoramic ECG display tool plus conventional 12-lead electrocardiogram (ECG) versus 12-lead ECG alone by UK critical care nurses who were members of the British Association of Critical Care Nurses (BACCN). Critically ill patients are prone to myocardial ischaemia. Symptoms may be masked by sedation or analgesia, and ECG changes may be the only sign. Critical care nurses have an essential role in detecting ECG changes promptly. Despite this, critical care nurses may lack expertise in interpreting ECGs and myocardial ischaemia often goes undetected by critical care staff. British Association of Critical Care Nurses (BACCN) members were invited to complete an online survey to evaluate the analysis of two sets of eight ECGs displayed alone and with the new display device. Data from 82 participants showed diagnostic accuracy improved from 67·1% reading ECG traces alone, to 96·0% reading ECG plus Panoramic ECG display tool (P < 0·01, significance level α = 0·05). Participants' diagnostic certainty score rose from 41·7% reading ECG alone to 66·8% reading ECG plus Panoramic ECG display tool (P < 0·01, α = 0·05). The Panoramic ECG display tool improves both accuracy and certainty of detecting ST segment changes among critical care nurses, when compared to conventional 12-lead ECG alone. This benefit was greatest with early ischaemic changes. Critical care nurses who are least confident in reading conventional ECGs benefit the most from the new display. Critical care nurses have an essential role in the monitoring of critically ill patients. However, nurses do not always have the expertise to detect subtle ischaemic ECG changes promptly. Introduction of the Panoramic ECG display tool into clinical practice could lead to patients receiving treatment for myocardial ischaemia sooner with the potential for reduction in morbidity and mortality. © 2012 The Authors. Nursing in Critical Care �

Intestinal obstruction caused by Taenia taeniaeformis infection in a cat.

PubMed

Wilcox, Rebbecca S; Bowman, Dwight D; Barr, Stephen C; Euclid, James M

2009-01-01

An adult domestic shorthair (DSH) cat was presented with acute vomiting, anorexia, lethargy, and dyspnea. The cat's clinical status worsened over 24 hours with conservative medical management. An exploratory celiotomy was performed. Acute intestinal obstruction resulting from infection with Taenia (T.) taeniaeformis was diagnosed. Surgical removal of the cestodes via multiple enterotomies resolved the obstruction. This paper reports, for the first time, small intestinal obstruction caused by T. taeniaeformis infection in a cat.

Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine.

PubMed

Ansari, Fariheen Aisha; Ali, Shaikh Nisar; Arif, Hussain; Khan, Aijaz Ahmed; Mahmood, Riaz

2017-01-01

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents?

PubMed

Hunter, A J; Mackay, K B; Rogers, D C

1998-02-01

A general consensus is being reached on the use of a combination of mortality and functional end-points in clinical trials of neuroprotective agents. However, to date, few preclinical studies have examined the effects of putative neuroprotective agents on functional outcome after ischaemia. The data described in this review show the importance of combining both histopathological and neurobehavioural studies when evaluating the neuroprotective efficacy of anti-ischaemic agents in animal models of cerebral ischaemia. Here, Jackie Hunter, Ken Mackay and Derek Rogers argue that measures of functional improvement in models of ischaemia should be incorporated to characterize further the neuroprotection afforded by a compound that could aid the selection of doses and end-point measures in early clinical trials.

Outcomes of Patients with Critical Limb Ischaemia in the EUCLID Trial.

PubMed

Norgren, Lars; Patel, Manesh R; Hiatt, William R; Wojdyla, Daniel M; Fowkes, F Gerry R; Baumgartner, Iris; Mahaffey, Kenneth W; Berger, Jeffrey S; Jones, W Schuyler; Katona, Brian G; Held, Peter; Blomster, Juuso I; Rockhold, Frank W; Björck, Martin

2018-01-01

Critical limb ischaemia (CLI) implies an increased risk of cardiovascular morbidity and mortality, and the optimal antithrombotic treatment is not established. The EUCLID trial investigated the effect of monotherapy with ticagrelor versus clopidogrel in 13,885 patients with peripheral artery disease (PAD); the primary endpoint was cardiovascular death, myocardial infarction, or ischaemic stroke. Patients planned for revascularisation or amputation within 3 months, were excluded. This analysis focuses on the subgroup with CLI, defined by rest pain (58.8%), major (9.0%) or minor (32.2%) tissue loss. In EUCLID, 643 patients (4.6%) had CLI at baseline. Diabetes mellitus was more common in the CLI group, while coronary disease, carotid disease, and hypertension were more common in the non-CLI group. A majority of CLI patients (62.1%) had only lower extremity PAD. In patients enrolled on the ankle brachial index (ABI) criteria, ABI was 0.55 ± 0.21 (mean ± SD) for those with CLI versus 0.63 ± 0.15 for those without CLI. The primary efficacy endpoint significantly increased among patients with CLI compared with those without CLI with a rate of 8.85 versus 4.28/100 patient years (adjusted for baseline characteristics hazard ratio [HR] 1.43 [95% CI 1.16-1.76]; p = 0.0009). When acute limb ischaemia requiring hospitalisation was added to the model, significant differences remained (adjusted HR 1.38, [95% CI 1.13-1.69]; p = 0.0016). The 1 year mortality was 8.9%. A trend towards increased lower limb revascularisation among those with CLI was observed. Bleeding (TIMI major, fatal, intracranial) did not differ between those with and without CLI. Nearly 5% of patients enrolled in EUCLID had CLI at baseline. Milder forms of CLI dominated, a result of the trial design. Patients with CLI had a significantly higher rate of cardiovascular mortality and morbidity versus those without CLI. Further efforts are required to reduce the risk of cardiovascular events in PAD

Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

PubMed

Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

2016-01-01

Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Leptospirosis complicating with acute large bowel gangrene: a case report.

PubMed

Zamri, Z; Shaker, A H; Razman, J

2012-01-01

Leptospirosis is a zoonosis with worldwide distribution. It is often referred to as swineherd's disease, swamp fever or mud fever. In recent years there is increase incidence in leptospirosis in human. The incidence varies from sporadic in temperate zones to endemic in the tropical countries. Leptospirosis generally present with features of bacterial infection in acute phase following with multi organs complications. Acute bowel ischaemia with perforation following leptospirosis is a rare presentation . To the best of our knowledge, this is the first case report of such condition. The surgical management of this rare incidence will be discussed.

Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

PubMed Central

Huddam, B; Haberal, N; Koçak, G; Ortabozkoyun, L; Şenes, M; Akdoğan, MF; Denizli, N; Duranay, M

2013-01-01

Introduction Despite the developments in modern medicine, acute renal injury is still a challenging and common health problem. It is well known that ischaemia and reperfusion takes place in pathological mechanisms. Efforts to clarify the pathophysiology and interventions to improve outcomes are essential. Our study aimed to investigate whether the prophylactic use of paricalcitol is beneficial in renal ischaemia/reperfusion (I/R) injury. Methods Twenty-four Wistar albino rats were assigned randomly to four groups. Right nephrectomies were performed at the time of renal arterial clamping. Sham surgery was performed on the rats in group 1. For the rats in group 2, the left renal artery was clamped for 45 minutes. The rats in group 3 received paricalcitol for seven days (0.2µg/kg/day); following this, a right nephrectomy and left renal arterial clamping were not performed. The rats in group 4 received paricalcitol for seven days (0.2µg/ kg/day); following this, a right nephrectomy and left renal arterial clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric oxide metabolites, serum urea and creatinine levels were measured for all four groups. Results In group 4, there were some improvements in terms of TBARS, nitrite, nitrate, superoxide dismutase and creatinine levels. In the histopathological evaluation, paricalcitol therapy improved tubular necrosis and medullar congestion but there was no significant difference in terms of tubular cell swelling, cellular vacuolisation or general damage. Immunohistopathological examination revealed lower scores for vascular endothelial growth factor in the group 4 rats than in group 2. Conclusions Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated. PMID:24112495

Endothelial immunomediated reactivity in acute cardiac ischaemia: Role of endothelin 1, interleukin 8 and NT-proBNP in patients affected by unstable angina pectoris

PubMed Central

Caroselli, Costantino; De Rosa, Rosario; Tanzi, Pietro; Rigatelli, Alberto; Bruno, Guglielmo

2016-01-01

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known. The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels. Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student’s t-test and a Mann-Whitney U test were performed. Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA. Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs. In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs. PMID:26684625

Endothelial immunomediated reactivity in acute cardiac ischaemia: Role of endothelin 1, interleukin 8 and NT-proBNP in patients affected by unstable angina pectoris.

PubMed

Caroselli, Costantino; De Rosa, Rosario; Tanzi, Pietro; Rigatelli, Alberto; Bruno, Guglielmo

2016-09-01

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs. © The Author(s) 2015.

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

PubMed Central

Stavrou, Brigitte M; Beck, Caroline; Flores, Nicholas A

2001-01-01

The structural conformation of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap4A and Ap5A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap4A and Ap5A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap4A has any electrophysiological or antiarrhythmic effects during ischaemia. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 μM Ap4A and Ap5A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 μM Ap4A were studied during global low-flow ischaemia and reperfusion. At pH 7.4, Ap4A and Ap5A increased action potential duration (APD95) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap4A increased RP but the effects of Ap4A and Ap5A on perfusion pressure were attenuated. During ischaemia, Ap4A had no antiarrhythmic or electrophysiological effects. These data demonstrate the importance of extracellular pH in influencing the effects of Ap4A and Ap5A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia. PMID:11588119

Self-reported symptoms and risk factors for digital ischaemia among international world-class beach volleyball players.

PubMed

Van De Pol, Daan; Alaeikhanehshir, Sena; Maas, Mario; Kuijer, P Paul F M

2016-01-01

The prevalence of ischaemia-related symptoms is remarkably high among elite indoor volleyball players. Since the exposure to sport-specific demands may be higher in beach volleyball compared to indoor volleyball, the aim of this study was to assess the prevalence of ischaemia-related symptoms and associated risk factors among world-class beach volleyball players. Therefore, a questionnaire survey was performed among beach volleyball players active during the 2013 Grand Slam Beach Volleyball in the Netherlands. In total, 60 of the 128 beach volleyball players (47%) participated: 26 males and 34 females from 17 countries. The self-reported prevalence of cold or blue or pale digits in the dominant hand during or immediately after practice or competition was 38% (n = 23). Two risk factors were independently associated with symptoms of blue or pale digits: more than 14 years playing volleyball (odds ratio (OR) 4.42, 90% confidence interval (90% CI) 1.30-15.07) and sex (female) (OR 4.62, 90% CI 1.15-18.57). In conclusion, the prevalence of symptoms associated with digital ischaemia is high among international world-class beach volleyball players. Female sex and the length of the volleyball career were independently associated with an increased risk of ischaemia-related symptoms. The high prevalence of these seemingly innocuous symptoms and possible associated risk factors warrant regular monitoring since early detection can potentially prevent thromboembolic complications and irreversible tissue damage.

Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury.

PubMed

Cayli, Sevil; Ocakli, Seda; Senel, Ufuk; Eyerci, Nilnur; Delibasi, Tuncay

2016-02-01

The most significant complication of testicular ischaemia is loss of the testis, which may lead to infertility. Testicular ischaemia damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated protein aggregates. Despite recent advances, the factors leading to impairment of spermatogenesis owing to testicular ischaemia remain poorly understood. This study was undertaken to gain insight into the cellular and molecular mechanism underlying torsion induced germ cell apoptosis. Male rats were subjected to 2 h torsion, and testes were examined at 2, 4, 12 and 24 h after torsion repair (reperfusion). Ischaemia-reperfusion (IR) of the testes resulted in apoptosis which was revealed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique. At 12 h after torsion repair germ cell loss reached peak, then decreased at 24 h repair. Western blotting showed that apoptotic proteins (active caspase 3, caspase 9 and Bax) gradually was upregulated at 12 h reperfusion, however anti-apoptotic protein (Bcl2) was downregulated in the relevant IR treatment. Furthermore, Jab1/CSN5 expression was gradually upregulated and p97/VCP expression was downregulated in IR injury according to western blotting and immunohistochemistry. To test further whether polyubiquitination was also involved in IR injury, the expression of polyubiquitinated proteins was examined, which showed that polyubiquitinated proteins were significantly increased in IR injury. These finding suggest that p97/VCP and Jab1/CSN5 provide a novel signaling pathway for testicular ischaemia and may play an important role in IR injury induced cell death in rat testis.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

PubMed

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Bacteriotherapy of acute radiation sickness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mal'tsev, V.N.; Korshunov, V.M.; Strel'nikov, V.A.

1979-04-01

Acute sickness is associated with intestinal dysbacteriosis; there is a radical decrease in number of microorganisms of lactic fermentation (bifidobacterium, lactobacillus) and an increase in E. coli proteus, enterococcus, and clostridium. Extensive use is made of live microorganisms in the treatment of various diseases associated with intestinal dysbacteriosis; in the case of acute radiation sickness, yeast, colibacterin, and E. coli have been used. In a number of cases, such therapy increased survival and life expectancy of irradiated animals. In this study, microorganisms of lactic fermentation (lactobacillus, bifidobacterium) and colibacterin were used for treatment of acute radiation sickness.

[Acute compartment syndrome of the lower leg after ankle joint sprain. A case report].

PubMed

Angermann, P; Hoser, C; Lutz, M; Fink, C; Seykora, P

1998-03-01

In the field of traumatology, compartment syndromes of the lower extremity are often seen after fractures and direct injuries, or after ischaemia. Other causes include over-exertion and non-traumatic causes such as acute rhabdomyolysis, drug-induced myositis and eosinophilic myositis. This paper describes the clinical and MR course of a compartment syndrome following an ankle sprain.

Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury.

PubMed

Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

2017-01-01

Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation

Stem cells and their role in renal ischaemia reperfusion injury.

PubMed

Bagul, Atul; Frost, Jodie H; Drage, Martin

2013-01-01

Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

Intestinal lymphangiectasia in children. A favorable response to dietary modifications.

PubMed

Isa, Hasan M; Al-Arayedh, Ghadeer G; Mohamed, Afaf M

2016-02-01

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.

Intestinal volvulus in cetaceans.

PubMed

Begeman, L; St Leger, J A; Blyde, D J; Jauniaux, T P; Lair, S; Lovewell, G; Raverty, S; Seibel, H; Siebert, U; Staggs, S L; Martelli, P; Keesler, R I

2013-07-01

Intestinal volvulus was recognized as the cause of death in 18 cetaceans, including 8 species of toothed whales (suborder Odontoceti). Cases originated from 11 institutions from around the world and included both captive (n = 9) and free-ranging (n = 9) animals. When the clinical history was available (n = 9), animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3 of these animals (33%), there was a history of chronic gastrointestinal illness. The pathological findings were similar to those described in other animal species and humans, and consisted of intestinal volvulus and a well-demarcated segment of distended, congested, and edematous intestine with gas and bloody fluid contents. Associated lesions included congested and edematous mesentery and mesenteric lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential predisposing causes were recognized in most cases (13 of 18, 72%) but were variable. Further studies investigating predisposing factors are necessary to help prevent occurrence and enhance early clinical diagnosis and management of the condition.

Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.

PubMed

Kim, Myung-Gyu; Boo, Chang Su; Ko, Yoon Sook; Lee, Hee Young; Cho, Won Yong; Kim, Hyoung Kyu; Jo, Sang-Kyung

2010-09-01

Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI). Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done. Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery. Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis

PubMed Central

Becker, Felix; Kurmaeva, Elvira; Gavins, Felicity N. E.; Stevenson, Emily V.; Navratil, Aaron R.; Jin, Long; Tsunoda, Ikuo; Orr, A. Wayne; Alexander, Jonathan S.; Ostanin, Dmitry V.

2016-01-01

Background Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their role in intestinal IAL has never been studied mechanistically. We investigated contributions of monocytes/MΦ to the development of intestinal inflammation and IAL. Methods Because inflammatory monocytes express CC chemokine receptor 2 (CCR2), we used CCR2 diphtheria toxin receptor transgenic (CCR2.DTR) mice, in which monocytes can be depleted by diphtheria toxin injection, and CCR2−/− mice, which have reduced circulating monocytes. Acute or chronic colitis was induced by dextran sodium sulfate or adoptive transfer of CD4+CD45RBhigh T cells, respectively. Intestinal inflammation was assessed by flow cytometry, immunofluorescence, disease activity, and histopathology, whereas IAL was assessed by lymphatic vessel morphology and density. Results We demonstrated that intestinal MΦ expressed vascular endothelial growth factor-C/D. In acute colitis, monocyte-depleted mice were protected from intestinal injury and showed reduced IAL, which was reversed after transfer of wild-type monocytes into CCR2−/− mice. In chronic colitis, CCR2 deficiency did not attenuate inflammation but reduced IAL. Conclusions We propose a dual role of MΦ in (1) promoting acute inflammation and (2) contributing to IAL. Our data suggest that intestinal inflammation and IAL could occur independently, because IAL was reduced in the absence of monocytes/MΦ, even when inflammation was present. Future inflammatory bowel disease therapies might exploit promotion of IAL and suppression of MΦ independently, to restore lymphatic clearance and reduce inflammation. PMID:26950310

Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

PubMed

Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

2013-10-25

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

Weak Links in the Early Chain of Care of Acute Lower Limb Ischaemia in Terms of Recognition and Emergency Management.

PubMed

Langenskiöld, M; Smidfelt, K; Karlsson, A; Bohm, C; Herlitz, J; Nordanstig, J

2017-08-01

Acute lower limb ischaemia (ALLI) is a potentially fatal, limb threatening medical emergency. Early treatment is essential for a good outcome. The aim was to describe the early chain of care in ALLI focusing on lead times and emergency management in order to identify weak links for improvement. This was a retrospective, descriptive case study. This study analysed the medical records of all patients with a main discharge diagnosis of ALLI between January 2009 and December 2014. Predetermined emergency care data on lead times, diagnosis recognition, presenting symptoms, emergency care treatment and outcome were collected for patients who were transported by the Emergency Medical Service (EMS) and those who were not. In total, 552 medical records were audited of which 195 patients fulfilled the inclusion criteria and were analysed. Among them were 117 (60%) transported by the EMS. The median time from symptom onset to revascularisation was 23 (interquartile range [IQR] 10-55; EMS transported) and 93 (IQR 42-152, not EMS transported) hours (p < .01). The time from symptom onset to arrival in hospital was 5 (IQR 2-26; EMS transported) and 48 (IQR 6-108; not EMS transported) hours. After arrival in hospital, the median time to first doctor evaluation was 51 (IQR 28-90; EMS transported) and 80 (IQR 44-169; not EMS transported) minutes, p = .01. Low molecular weight heparin (LMWH) was given to 72% of patients in the emergency department (ED) and a multivariate analysis showed that the use of LMWH was associated with a more favourable outcome. Both the time spent in the ED and the time from the onset of symptoms to revascularisation were considerably longer than optimal. Time delays in the early treatment chain can mainly be attributed to "patient delay" and a considerable time spent in hospital before revascularisation. The use of LMWH as an integral part of ED management was associated with a better outcome. Copyright © 2017 European Society for Vascular Surgery

Intestinal Rehabilitation Programs in the Management of Pediatric Intestinal Failure and Short Bowel Syndrome.

PubMed

Merritt, Russell J; Cohran, Valeria; Raphael, Bram P; Sentongo, Timothy; Volpert, Diana; Warner, Brad W; Goday, Praveen S

2017-11-01

Intestinal failure is a rare, debilitating condition that presents both acute and chronic medical management challenges. The condition is incompatible with life in the absence of the safe application of specialized and individualized medical therapy that includes surgery, medical equipment, nutritional products, and standard nursing care. Intestinal rehabilitation programs are best suited to provide such complex care with the goal of achieving enteral autonomy and oral feeding with or without intestinal transplantation. These programs almost all include pediatric surgeons, pediatric gastroenterologists, specialized nurses, and dietitians; many also include a variety of other medical and allied medical specialists. Intestinal rehabilitation programs provide integrated interdisciplinary care, more discussion of patient management by involved specialists, continuity of care through various treatment interventions, close follow-up of outpatients, improved patient and family education, earlier treatment of complications, and learning from the accumulated patient databases. Quality assurance and research collaboration among centers are also goals of many of these programs. The combined and coordinated talents and skills of multiple types of health care practitioners have the potential to ameliorate the impact of intestinal failure and improve health outcomes and quality of life.

Attenuation of changes in capillary fine structure and leukocyte adhesion improves muscle performance following chronic ischaemia in rats

PubMed Central

Hudlická, O; Garnham, A; Shiner, R; Egginton, S

2008-01-01

Acute ischaemia–reperfusion disrupts capillary fine structure and increases leukocyte adhesion in postcapillary venules. We determined whether chronic muscle ischaemia has similar consequences, and whether it is possible to ameliorate its effect on muscle performance. Following ischaemia (unilateral ligation, common iliac artery) rat hindlimb muscles were examined without other intervention or following treatment with an xanthine oxidase inhibitor (allopurinol), a Na+/H+ exchange blocker (amiloride), or an oxygen free radical scavenger (vitamin E). No significant leukocyte adhesion or rolling, nor changes in capillary fine structure were observed 3 days postsurgery, when limb use was limited. However, leukocyte rolling and adhesion almost trebled by 7 days (P < 0.001), when normal gait was largely restored. Capillary fine structure was disturbed over a similar time course, e.g. relative endothelial volume (control 46%, 7 days 61%; P < 0.05), that resolved by 5 weeks. Where activity was increased by mild electrical stimulation 3 days after ligation muscles showed enhanced capillary swelling (endothelial volume 66%versus 50%, P < 0.005), but improved fatigue index (52%versus 16%, P < 0.001) as a result of greater blood flow. Muscle fatigue after ligation was related to the extent of contraction-induced hyperaemia (R2= 0.725), but not capillary swelling. Amiloride, and to a lesser extent allopurinol but not vitamin E, significantly decreased leukocyte rolling and adhesion, as well as capillary endothelial swelling. We conclude that increased activity of ischaemic muscles on recovery is likely to accentuate acidosis accompanying changes in microcirculation and contribute to enhanced muscle fatigue, whereas formation of oxygen free radicals may be attenuated by endogenous protective mechanisms. PMID:18755748

Intestinal lesions in dogs with acute hemorrhagic diarrhea syndrome associated with netF-positive Clostridium perfringens type A.

PubMed

Leipig-Rudolph, Miriam; Busch, Kathrin; Prescott, John F; Mehdizadeh Gohari, Iman; Leutenegger, Christian M; Hermanns, Walter; Wolf, Georg; Hartmann, Katrin; Verspohl, Jutta; Unterer, Stefan

2018-04-01

Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex. Endoscopic biopsies of the gastrointestinal tract were taken and examined histologically (H&E, Giemsa), immunohistochemically ( Clostridium spp., parvovirus), and bacteriologically. The main findings were acute necrotizing and neutrophilic enterocolitis (9 of 10) with histologic detection of clostridia-like, gram-positive bacteria on the necrotic mucosal surface (9 of 10). Clostridium perfringens isolated from the duodenum was identified as type A (5 of 5) by multiplex PCR (5 of 5). In addition, each of the 5 genotyped isolates encoded the pore-forming toxin netF. Clostridium spp. (not C. perfringens) were cultured from duodenal biopsies in 2 of 9 control dogs. These findings suggest that the pore-forming netF toxin is responsible for the necrotizing lesions in the intestines of a significant proportion of dogs with AHDS. Given that the stomach was not involved in the process, the term "acute hemorrhagic diarrhea syndrome" seems more appropriate than the frequently used term "hemorrhagic gastroenteritis."

Acidic pre-conditioning suppresses apoptosis and increases expression of Bcl-xL in coronary endothelial cells under simulated ischaemia.

PubMed

Kumar, S; Reusch, H P; Ladilov, Y

2008-01-01

Ischaemic pre-conditioning has a powerful protective potential against ischaemia-induced cell death, and acidosis is an important feature of ischaemia and can lead to apoptosis. Here we tested whether pre-conditioning with acidosis, that is, acidic pre-conditioning (APC), may protect coronary endothelial cells (EC) against apoptosis induced by simulated ischaemia. For pre-conditioning, EC were exposed fo 40 min. to acidosis (pH 6.4) followed by a 14-hrs recovery period (pH 7.4) and finally treated for 2 hrs with simulated ischaemia (glucose-free anoxia at pH 6.4). Cells undergoing apoptosis were visualized by chromatin staining or by determination of caspase-3 activity Simulated ischaemia in untreated EC increased caspase-3 activity and the number of apoptotic cell (31.3 +/- 1.3%versus 3.9 +/- 0.6% in control). APC significantly reduced the rate of apoptosis (14.2 +/- 1.3%) and caspase-3 activity. Western blot analysis exploring the under lying mechanism leading to this protection revealed suppression of the endoplasmic reticulum- (reduced cleavage of caspase-12) and mitochondria-mediated (reduced cytochrome C release) pathways of apoptosis. These effects were associated with an over-expression of the anti-apoptotic protein Bcl-xL 14 hrs after APC, whereas no effect on the expression of Bcl-2, Bax, Bak, procaspase-12, reticulum-localized chaperones (GRP78, calreticulin), HSP70, HSP32 and HSP27 could be detected. Knock-down of Bcl-xL by siRNA-treatment prevented the protective effect of APC. In conclusion, short acidic pre-treatment can protect EC against ischaemic apoptosis. The mechanism of this protection consists of suppression of the endoplasmic reticulum- and mitochondria-mediated pathways. Over-expression of the anti apoptotic protein Bcl-xL is responsible for the increased resistance to apoptosis during ischaemic insult.

Intestinal Helminths Regulate Lethal Acute Graft Versus Host Disease and Preserve Graft Versus Tumor Effect in Mice

PubMed Central

Li, Yue; Chen, Hung-lin; Bannick, Nadine; Henry, Michael; Holm, Adrian N.; Metwali, Ahmed; Urban, Joseph F.; Rothman, Paul B.; Weiner, George J.; Blazar, Bruce R.; Elliott, David E.; Ince, M. Nedim

2014-01-01

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor; GVT) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation, called graft-versus-host disease (GVHD). High dose steroids or other immune suppressives are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT and prevent mortality in bone marrow transplantation. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected Balb/C recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation along with reduction in GVHD lethality and maintenance of GVT. H. polygyrus colonization promoted the survival of TGFβ generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGFβ-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD, when T cells unresponsive to TGFβ-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD, employing regulatory T cells and TGFβ-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT. PMID:25527786

Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia.

PubMed

Whittington, Hannah J; McAndrew, Debra J; Cross, Rebecca L; Neubauer, Stefan; Lygate, Craig A

2016-01-01

Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia. CrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates (76% of baseline vs. 59%, respectively, P = 0.02). Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia (104% of baseline vs. 67%, P = 0.0007). The cardioprotective effect of hypothermic high K+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts (76% of baseline vs. 55% of baseline as seen in WT hearts, P = 0.02). These observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury.

Ameliorating effects of dexpanthenol in cerebral ischaemia reperfusion induced injury in rat brain.

PubMed

Zakaria, Mohammad Mehdi Hosseinian; Hajipour, Babak; Khodadadi, Ali; Afshari, Fatemeh

2011-09-01

To study the attenuating effect of Dexpanthenol (Dxp) provitamin B5 on neuronal damage after cerebral ischaemia/reperfusion. This was a randomized, controlled experimental study conducted at the Islamic Azad University, Tabriz, Iran, from April to September 2008. Male wistar rats were divided into 4 groups randomly (n=13): 1- sham group, Group 2 :two hours occlusion of middle cerebral artery (MCA) and 24 hours reperfusion. Group 3: two hours occlusion of MCA and 24 hours reperfusion + Dxp (250mg/kg) since 3 days before ischaemia. Group 4: two hours occlusion of MCA and 24 hours reperfusion which had received Dxp (500mg/kg) since 3 days before ischaemia. Glutathione (GSH) and malondialdehyde (MDA) levels were studied in brain tissue and numbers of cornu ammonis (CA1 and CA3) pyramidal neurons were studied with light microscopy. The GSH levels were significantly higher in groups 3 and 4 as compared with group 2. In group 3 and group 4 animals, the MDA levels were significantly lower than in group 2 (P < 0.05). Numbers of CA1 and CA3 neurons were completely normal in appearance in the group 1. The surviving neurons in the CA1 and CA3 subfield were markedly decreased in number, in group 2 (P < 0.05). Our pathologic and biochemical study has proven positive effect of Dxp on protection of cerebral tissue after I/R. The present findings correlate with previous studies on the protective effects of Dxp against cell and tissue injury by I/R.

Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

PubMed

Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

2015-05-27

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis

PubMed Central

Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

2015-01-01

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis. PMID:26013555

Added prognostic value of ischaemic threshold in radionuclide myocardial perfusion imaging: a common-sense integration of exercise tolerance and ischaemia severity.

PubMed

Marini, Cecilia; Acampa, Wanda; Bauckneht, Matteo; Daniele, Stefania; Capitanio, Selene; Cantoni, Valeria; Fiz, Francesco; Zampella, Emilia; Dib, Bassam; Assante, Roberta; Bruzzi, Paolo; Sambuceti, Gianmario; Cuocolo, Alberto

2015-04-01

Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD). We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2-4) in 180, moderate (SDS 5-7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information. Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.

Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.

PubMed

Sutherland, Brad A; Harrison, Joanne C; Nair, Shiva M; Sammut, Ivan A

2013-01-01

Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

Effect of ceramide-1-phosphate transfer protein on intestinal bacterial translocation in severe acute pancreatitis.

PubMed

Wang, Jiang; Li, Chang; Jiang, Yingjian; Zheng, Hongmei; Li, Dehui; Liang, Yibo; Deng, Wensheng; Zhang, Dianliang

2017-02-01

The aim of the study was to investigate the effects of ceramide-1-phosphate transfer protein (CPTP) on the intestinal epithelial tight junction proteins in patients with severe acute pancreatitis (SAP). Fifty patients with SAP were classified into two groups according to the presence of bacterial translocation (BT) in the blood. Thirty healthy individuals were included in the control group. The presence of BT was analyzed by polymerase chain reaction. The expression of tight junction proteins and CPTP was determined using immunohistochemistry and western blotting. Bacterial DNA was detected in the peripheral blood of 62.0% of the patients with SAP. The expression of CPTP and tight junction proteins in SAP patients was lower than that in healthy controls. Among the patients with SAP, those positive for BT(+) showed a lower level of CPTP and occluding (OC) and zonula occludens-1 (ZO-1) expression and a higher level of IVA cPLA2 expression than BT(-) patients. Moreover, the expression of CPTP was significantly associated with ZO-1 and showed a negative correlation with expression of IVA cPLA2 in SAP-BT(+) patients. CPTP affects the expression of tight junction proteins and may protects the intestinal epithelial barrier by downregulating the expression of IVA cPLA2. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Preservation of the gut by preoperative carbohydrate loading improves postoperative food intake.

PubMed

Luttikhold, Joanna; Oosting, Annemarie; van den Braak, Claudia C M; van Norren, Klaske; Rijna, Herman; van Leeuwen, Paul A M; Bouritius, Hetty

2013-08-01

A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury

PubMed Central

Husain, Kareem D.; Stromberg, Paul E.; Woolsey, Cheryl A.; Turnbull, Isaiah R.; Dunne, W. Michael; Javadi, Pardis; Buchman, Timothy G.; Karl, Irene E.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2005-01-01

Objectives The aim of this study was to determine the effects of acute lung injury (ALI) on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Design Randomized, controlled study. Setting University research laboratory. Subjects Genetically inbred mice. Interventions Following induction of ALI, gut epithelial proliferation and apoptosis was assessed in a) C3H/HeN wild type and C3H/HeJ mice, that lack functional toll-like receptor 4 (TLR4, n=17), b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-α (TNFα) or control antibody (n=22) and c) C57Bl/6 wild type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n=21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n=24) as well as in a timecourse analysis following a fixed injury (n=18). Measurements and Main Results ALI caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-TNFα antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe ALI. Changes in both gut epithelial proliferation and death were apparent within 12 hours, but proliferation was decreased 36 hours following ALI while apoptosis returned to normal. Conclusions ALI causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving TLR4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the gut

Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vavassori, Vittorio; Fiorino, Claudio; Rancati, Tiziana

2007-04-01

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132more » patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

PubMed

Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Flaherty, Katie; Havard, Diane; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Montgomery, Alan A; Pocock, Stuart J; Randall, Marc; Ranta, Annemarei; Robinson, Thompson G; Scutt, Polly; Venables, Graham S; Sprigg, Nikola

2018-03-03

Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was

Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition.

PubMed

Ning, Jian-Wen; Zhang, Yan; Yu, Mo-Sang; Gu, Meng-Li; Xu, Jia; Usman, Ali; Ji, Feng

2017-08-15

Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1β, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1β-converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1β, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. Rats in the SAP group had higher serum levels of IL-1β and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1β and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. Emodin alleviated pancreatic and intestinal mucosa

A single point acupuncture treatment at large intestine meridian: a randomized controlled trial in acute tonsillitis and pharyngitis.

PubMed

Fleckenstein, Johannes; Lill, Christian; Lüdtke, Rainer; Gleditsch, Jochen; Rasp, Gerd; Irnich, Dominik

2009-09-01

One out of 4 patients visiting a general practitioner reports of a sore throat associated with pain on swallowing. This study was established to examine the immediate pain alleviating effect of a single point acupuncture treatment applied to the large intestine meridian of patients with sore throat. Sixty patients with acute tonsillitis and pharyngitis were enrolled in this randomized placebo-controlled trial. They either received acupuncture, or sham laser acupuncture, directed to the large intestine meridian section between acupuncture points LI 8 and LI 10. The main outcome measure was the change of pain intensity on swallowing a sip of water evaluated by a visual analog scale 15 minutes after treatment. A credibility assessment regarding the respective treatment was performed. The pain intensity for the acupuncture group before and immediately after therapy was 5.6+/-2.8 and 3.0+/-3.0, and for the sham group 5.6+/-2.5 and 3.8+/-2.5, respectively. Despite the articulation of a more pronounced improvement among the acupuncture group, there was no significant difference between groups (Delta=0.9, confidence interval: -0.2-2.0; P=0.12; analysis of covariance). Patients' satisfaction was high in both treatment groups. The study was prematurely terminated due to a subsequent lack of suitable patients. A single acupuncture treatment applied to a selected area of the large intestine meridian was no more effective in the alleviation of pain associated with clinical sore throat than sham laser acupuncture applied to the same area. Hence, clinically relevant improvement could be achieved. Pain alleviation might partly be due to the intense palpation of the large intestine meridian. The benefit of a comprehensive acupuncture treatment protocol in this condition should be subject to further trials.

Angiotensin converting enzyme inhibition in chronic stable angina: effects on myocardial ischaemia and comparison with nifedipine.

PubMed Central

Ikram, H.; Low, C. J.; Shirlaw, T. M.; Foy, S. G.; Crozier, I. G.; Richards, A. M.; Khurmi, N. S.; Horsburgh, R. J.

1994-01-01

OBJECTIVES--To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease. DESIGN--Placebo controlled, double blind, latin square design. SETTING--Regional cardiology service for a mixed urban and rural population. SUBJECTS--40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial. INTERVENTIONS--Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks. MAIN OUTCOME MEASURES AND RESULTS--Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0

Ischaemia-modified albumin: a marker of bacterial infection in hospitalized patients with cirrhosis.

PubMed

Giannone, Ferdinando A; Domenicali, Marco; Baldassarre, Maurizio; Bartoletti, Michele; Naldi, Marina; Laggetta, Maristella; Bertucci, Carlo; Colecchia, Antonio; Viale, Pierluigi; Bernardi, Mauro; Caraceni, Paolo

2015-11-01

Patients with cirrhosis present structural changes of human serum albumin (HSA) affecting non-oncotic functions. Ischaemia-modified albumin (IMA), which reflects the capacity to bind cobalt, has been associated to patient mortality during acute-on-chronic liver failure. This study aimed to assess whether circulating IMA is elevated in advanced cirrhosis and its relationship with severity of cirrhosis and specific complications. A total of 127 cirrhotic patients hospitalized for an acute complication of the disease and 44 healthy controls were enrolled. Plasma IMA and IMA to albumin ratio (IMAr) were measured with a cobalt-binding assay. HSA isoforms carrying post-transcriptional molecular changes were assessed with HPLC-ESI-MS. The effect of endotoxemia on IMA was evaluated in rats with CCl4 -cirrhosis. IMA/IMAr is significantly higher in cirrhotic patients than in controls, but no correlations were found with prognostic scores. IMA did not correlate with the altered HSA isoforms. Ascites, renal impairment and hepatic encephalopathy did not influence IMA/IMAr levels. In contrast, IMA/IMAr is significantly higher in infected than non-infected patients. ROC curves showed that IMA/IMAr had similar discriminating performances for bacterial infection as C-reactive protein (CRP). Moreover, CRP and IMA were independently associated with bacterial infection. Consistently, endotoxin injection significantly increased IMA in cirrhotic, but not in healthy rats. IMA is elevated in patients with advanced cirrhosis. The IMA level does not correlate with disease severity scores, but it is specifically associated to bacterial infection, showing a discriminating performance similar to CRP. Further investigations to assess IMA as a novel diagnostic test for bacterial infection are advocated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

THE COURSE OF ACUTE INTESTINAL INFECTIONS IN MONKEYS DURING THE ACTION OF IONISING RADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stasilevich, Z.K.

1963-04-01

The influence of sublethal x irradiation on the susceptibility of monkeys to acute intestinal infections (paratyphoid B fever, Heidelberg's salmonellosis and colienteritis) was studied. Experiments were carried out on 46 macaque monkeys, aged 2 1/2 to 3 yr. In monkeys subjected to a dose of 300 r there was an elevated susceptibility to paratyphoid B fever; however, the infectious process was not aggravated. Irradiation of animals with a similar dose aggravated the infectious process in Heidelberg's salmonellosis. In monkeys with colienteritis the above dose did not influence the natural immunity of animals to this disease. A clinically marked disease (colienteritis),more » with a lethal outcome was induced in monkeys irradiated with a dose of 445 r. (auth)« less

Influence of genetic variations in platelet glycoproteins and eNOS in the development of arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

PubMed

Carvalhais, Virginia; Ruivães, Ema; Pina-Cabral, Luis Bernardo; Mesquita, Bárbara; Oliveira, Flávio; Monteiro, Maria Céu; Criado, Maria Begoña

2016-12-01

Endothelial and platelet dysfunction increase the atherothrombotic risk in diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an important complication in diabetes mellitus. In the present work, type 2 diabetic patients were classified by a podiatrist into presence or absence of arterial ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak sequence of GPIbα may be associated with a higher risk of developing arterial ischaemia of lower limbs in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aniracetam, a pyrrolidinone-type cognition enhancer, attenuates the hydroxyl free radical formation in the brain of mice with brain ischaemia.

PubMed

Himori, N; Suzuki, T; Ueno, K

1995-03-01

We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (.OH) during ischaemia-reperfusion of mouse brain. The fact that brain ischeamia for 40 min followed by reperfusion increased .OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxybenzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring .OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg-1 showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mg kg-1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg-1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.

Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation

PubMed Central

Aherne, Carol M.; Collins, Colm B.; Eltzschig, Holger K.

2013-01-01

The intestinal epithelium is a dynamic barrier playing an active role in intestinal homeostasis and inflammation. Intestinal barrier function is dysregulated during inflammatory bowel disease (IBD), with epithelial cells playing a significant part in generating an inflammatory milieu through the release of signals that attract leukocytes to the intestinal lamina propria. However, it is increasingly appreciated that the intestinal epithelium mediates a counterbalancing response to drive resolution. Drawing analogies with neuronal development, where the balance of chemoattractive and chemorepellent signals is key to directed neuronal movement it has been postulated that such secreted cues play a role in leukocyte migration. Netrin-1 is one of the best-described neuronal guidance molecules, which has been shown to play a significant role in directed migration of leukocytes. Prior to our study the potential role of netrin-1 in IBD was poorly characterized. We defined netrin-1 as an intestinal epithelial-derived protein capable of limiting neutrophil recruitment to attenuate acute colitis. Our study highlights that the intestinal epithelium releases factors during acute inflammation that are responsible for fine-tuning the immune response. Exploration of these epithelial-mediated protective mechanisms will shed light on the complexity of the intestinal epithelial barrier in health and disease. PMID:24665394

Dietary glutamine prevents the loss of intestinal barrier function and attenuates the increase in core body temperature induced by acute heat exposure.

PubMed

Soares, Anne D N; Costa, Kátia A; Wanner, Samuel P; Santos, Rosana G C; Fernandes, Simone O A; Martins, Flaviano S; Nicoli, Jacques R; Coimbra, Cândido C; Cardoso, Valbert N

2014-11-28

Dietary glutamine (Gln) supplementation improves intestinal function in several stressful conditions. Therefore, in the present study, the effects of dietary Gln supplementation on the core body temperature (T core), bacterial translocation (BT) and intestinal permeability of mice subjected to acute heat stress were evaluated. Male Swiss mice (4 weeks old) were implanted with an abdominal temperature sensor and randomly assigned to one of the following groups fed isoenergetic and isoproteic diets for 7 d before the experimental trials: group fed the standard AIN-93G diet and exposed to a high ambient temperature (39°C) for 2 h (H-NS); group fed the AIN-93G diet supplemented with l-Gln and exposed to a high temperature (H-Gln); group fed the standard AIN-93G diet and not exposed to a high temperature (control, C-NS). Mice were orally administered diethylenetriaminepentaacetic acid radiolabelled with technetium (99mTc) for the assessment of intestinal permeability or 99mTc-Escherichia coli for the assessment of BT. Heat exposure increased T core (approximately 41°C during the experimental trial), intestinal permeability and BT to the blood and liver (3 h after the experimental trial) in mice from the H-NS group relative to those from the C-NS group. Dietary Gln supplementation attenuated hyperthermia and prevented the increases in intestinal permeability and BT induced by heat exposure. No correlations were observed between the improvements in gastrointestinal function and the attenuation of hyperthermia by Gln. Our findings indicate that dietary Gln supplementation preserved the integrity of the intestinal barrier and reduced the severity of hyperthermia during heat exposure. The findings also indicate that these Gln-mediated effects occurred through independent mechanisms.

Intestinal helminths regulate lethal acute graft-versus-host disease and preserve the graft-versus-tumor effect in mice.

PubMed

Li, Yue; Chen, Hung-Lin; Bannick, Nadine; Henry, Michael; Holm, Adrian N; Metwali, Ahmed; Urban, Joseph F; Rothman, Paul B; Weiner, George J; Blazar, Bruce R; Elliott, David E; Ince, M Nedim

2015-02-01

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor [GVT]) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation called graft-versus-host disease (GVHD). High-dose steroids or other immunosuppressive drugs are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT, and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT, and prevent mortality in BMT. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected BALB/c recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation and reduced GVHD-related mortality, but maintained GVT. H. polygyrus colonization promoted the survival of TGF-β-generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGF-β-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD when T cells unresponsive to TGF-β-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD using Tregs and TGF-β-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT. Copyright © 2015 by The American Association of Immunologists, Inc.

Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia.

PubMed

Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S

1994-04-01

The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate

Burns, inflammation, and intestinal injury: protective effects of an anti-inflammatory resuscitation strategy.

PubMed

Costantini, Todd W; Peterson, Carrie Y; Kroll, Lauren; Loomis, William H; Putnam, James G; Wolf, Paul; Eliceiri, Brian P; Baird, Andrew; Bansal, Vishal; Coimbra, Raul

2009-12-01

Intestinal barrier breakdown after severe burn can lead to intestinal inflammation, which may act as the source of the systemic inflammatory response. In vitro intestinal cell studies have shown that mitogen-activated protein kinase (MAPK) signaling is an important modulator of intestinal inflammation. We have previously observed that pentoxifylline (PTX) attenuates burn-induced intestinal permeability and tight junction breakdown. We hypothesized that PTX would limit intestinal barrier breakdown and attenuate inflammatory signaling via the MAPK pathway. Male balb/c mice underwent 30% total body surface area full-thickness steam burn. Immediately after burn, animals received an intraperitoneal injection of PTX (12.5 mg/kg) in normal saline or normal saline alone. In vivo intestinal permeability to 4 kDa fluorescein isothiocyanate-dextran was measured. Intestinal extracts were obtained to measure interleukin-6 by enzyme-linked immunosorbent assay, and phosphorylated p38 MAPK, p38 MAPK, phosphorylated extracellular signal-related kinase (1/2) (ERK (1/2)), and ERK (1/2) by immunoblotting. Acute lung injury was assessed by histology at 24 hours after burn. Administration of PTX immediately after injury attenuated burn-induced intestinal permeability. PTX also decreased the burn-induced phosphorylation of p38 MAPK and decreased phosphorylation of ERK (1/2) at 2 hours and 24 hours after injury. Animals given PTX had decreased intestinal interleukin-6 levels. A single dose of PTX also decreased histologic lung injury at 24 hours after burn. PTX attenuates burn-induced intestinal permeability and subsequent intestinal inflammation. Use of PTX after burn was also associated with decreased acute lung injury. Because of its compelling anti-inflammatory effects, PTX may be an ideal candidate for use as an immunomodulatory adjunct to resuscitation fluid.

Preservation of Intestinal Structural Integrity by Zinc Is Independent of Metallothionein in Alcohol-Intoxicated Mice

PubMed Central

Lambert, Jason C.; Zhou, Zhanxiang; Wang, Lipeng; Song, Zhenyuan; McClain, Craig J.; Kang, Y. James

2004-01-01

Intestinal-derived endotoxins are importantly involved in alcohol-induced liver injury. Disruption of intestinal barrier function and endotoxemia are common features associated with liver inflammation and injury due to acute ethanol exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This study was designed to determine the inhibitory effect of zinc on alcohol-induced endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is independent of MT. MT knockout (MT-KO) mice were administered three oral doses of zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol administration caused liver injury as determined by increased serum transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of tumor necrosis factor (TNF-α). Increased plasma endotoxin levels were detected in ethanol-treated animals whose small intestinal structural integrity was compromised as determined by microscopic examination. Zinc supplementation significantly inhibited acute ethanol-induced liver injury and suppressed hepatic TNF-α production in association with decreased circulating endotoxin levels and a significant protection of small intestine structure. As expected, MT levels remained undetectable in the MT-KO mice under the zinc treatment. These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT. PMID:15161632

Intestinal Rotation Abnormalities and Midgut Volvulus.

PubMed

Langer, Jacob C

2017-02-01

Rotation abnormalities may be asymptomatic or may be associated with obstruction caused by bands, midgut volvulus, or associated atresia or web. The most important goal of clinicians is to determine whether the patient has midgut volvulus with intestinal ischemia, in which case an emergency laparotomy should be done. If the patient is not acutely ill, the next goal is to determine whether the patient has a narrow-based small bowel mesentery. In general, the outcomes for children with a rotation abnormality are excellent, unless there has been midgut volvulus with significant intestinal ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumour ischaemia by interferon-γ resembles physiological blood vessel regression.

PubMed

Kammertoens, Thomas; Friese, Christian; Arina, Ainhoa; Idel, Christian; Briesemeister, Dana; Rothe, Michael; Ivanov, Andranik; Szymborska, Anna; Patone, Giannino; Kunz, Severine; Sommermeyer, Daniel; Engels, Boris; Leisegang, Matthias; Textor, Ana; Fehling, Hans Joerg; Fruttiger, Marcus; Lohoff, Michael; Herrmann, Andreas; Yu, Hua; Weichselbaum, Ralph; Uckert, Wolfgang; Hübner, Norbert; Gerhardt, Holger; Beule, Dieter; Schreiber, Hans; Blankenstein, Thomas

2017-05-04

The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other haematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumour regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. Intravital microscopy revealed IFNγ-induced regression of the tumour vasculature, resulting in arrest of blood flow and subsequent collapse of tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike haemorrhagic necrosis induced by tumour necrosis factor. The early events of IFNγ-induced tumour ischaemia resemble non-apoptotic blood vessel regression during development, wound healing or IFNγ-mediated, pregnancy-induced remodelling of uterine arteries. A better mechanistic understanding of how solid tumours are rejected may aid the design of more effective protocols for adoptive T-cell therapy.

Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

PubMed

Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

2016-04-01

Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

[Intestinal volvulus. Case report and a literature review].

PubMed

Santín-Rivero, Jorge; Núñez-García, Edgar; Aguirre-García, Manuel; Hagerman-Ruiz-Galindo, Gonzalo; de la Vega-González, Francisco; Moctezuma-Velasco, Carla Rubi

2015-01-01

Small bowel volvulus is a rare cause of intestinal obstruction in adult patients. This disease is more common in children and its aetiology and management is different to that in adults. A 30 year-old male with sarcoidosis presents with acute abdomen and clinical data of intestinal obstruction. Small bowel volvulus is diagnosed by a contrast abdominal tomography and an exploratory laparotomy is performed with devolvulation and no intestinal resection. In the days following surgery, he developed a recurrent small bowel volvulus, which was again managed with surgery, but without intestinal resection. Medical treatment for sarcoidosis was started, and with his clinical progress being satisfactory,he was discharged to home. Making an early and correct diagnosis of small bowel volvulus prevents large intestinal resections. Many surgical procedures have been described with a high rate of complications. Therefore, conservative surgical management (no intestinal resection) is recommended as the best treatment with the lowest morbidity and mortality rate. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

PubMed Central

Almeida, Caroline de Souza; Andrade-Oliveira, Vinicius; Câmara, Niels Olsen Saraiva; Jacysyn, Jacqueline F.; Faquim-Mauro, Eliana L.

2015-01-01

Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a

Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

DTIC Science & Technology

2016-09-01

focal (GI tract) irradiation of mice on the bacterial and fungal microbiota. We have identified substantial changes in intestinal microbial...minimal acute symptoms, will develop long-term consequences of irradiation including permanent changes to bowel function and intestinal fibrosis, which...mice exposed to total body irradiation (TBI) or focal radiation to the GI tract. Timeline Status Site 1 (Stephen Shiao, MD, PhD) Site 2

The effect of dexpanthenol on experimentally induced ovarian ischaemia/reperfusion injury: a biochemical and histopathological evaluation.

PubMed

Soylu Karapinar, Oya; Pinar, Neslihan; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi; Şahin, Hanifi; Dolapçioğlu, Kenan

2017-03-01

The aim of this study was to evaluate the effect of two different doses of dexpanthenol (Dxp) onexperimentally induced ovarian ischaemia/reperfusion (I/R) injury ina rat model. Forty female rats were randomly divided into fivegroups: Group 1: sham operation; Group 2: 3-h ischaemia; Groups 3: 3-h ischaemia, 3-h reperfusion (I/R); Group 4: I/R + 300 mg/kg Dxp intraperitoneally (i.p) Group 5: I /R + 500 mg/kg Dxpi.p. Total anti-oxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), tissue malondialdehyde (MDA) and activities of glutathione peroxidase and catalase were calculated. Ovarian tissue damage was assessed using a histopathological scoring system. The TOS and OSI values were significantly lower in Group 5, as compared to Groups 2 and 3 (p < 0.05). The MDA levels in Group 1 and Group 5 were significantly lower than those in Group 3 (p < 0.05). CAT and GSH-Px activity was higher in Group 5 than in Group 2 and Group 3 (p = 0.00). Tissue damage scores were elevated in all the groups compared with sham group, but the treatment with the different doses of Dxp before reperfusion ameliorated the tissue damage scores. The results showed that Dxp reduced ovarian I/R injury.

Differential patterns of replacement and reactive fibrosis in pressure and volume overload are related to the propensity for ischaemia and involve resistin

PubMed Central

Chemaly, Elie R; Kang, Soojeong; Zhang, Shihong; McCollum, LaTronya; Chen, Jiqiu; Bénard, Ludovic; Purushothaman, K-Raman; Hajjar, Roger J; Lebeche, Djamel

2013-01-01

Pathological left ventricle (LV) hypertrophy (LVH) results in reactive and replacement fibrosis. Volume overload LVH (VOH) is less profibrotic than pressure overload LVH (POH). Studies attribute subendocardial fibrosis in POH to ischaemia, and reduced fibrosis in VOH to collagen degradation favouring dilatation. However, the mechanical origin of the relative lack of fibrosis in VOH is incompletely understood. We hypothesized that reduced ischaemia propensity in VOH compared to POH accounted for the reduced replacement fibrosis, along with reduced reactive fibrosis. Rats with POH (ascending aortic banding) evolved into either compensated-concentric POH (POH-CLVH) or dilated cardiomyopathy (POH-DCM); they were compared to VOH (aorta–caval fistula). We quantified LV fibrosis, structural and haemodynamic factors of ischaemia propensity, and the activation of profibrotic pathways. Fibrosis in POH-DCM was severe, subendocardial and subepicardial, in contrast with subendocardial fibrosis in POH-CLVH and nearly no fibrosis in VOH. The propensity for ischaemia was more important in POH versus VOH, explaining different patterns of replacement fibrosis. LV collagen synthesis and maturation, and matrix metalloproteinase-2 expression, were more important in POH. The angiotensin II-transforming growth-factor β axis was enhanced in POH, and connective tissue growth factor (CTGF) was overexpressed in all types of LVH. LV resistin expression was markedly elevated in POH, mildly elevated in VOH and independently reflected chronic ischaemic injury after myocardial infarction. In vitro, resistin is induced by angiotensin II and induces CTGF in cardiomyocytes. Based on these findings, we conclude that a reduced ischaemia propensity and attenuated upstream reactive fibrotic pathways account for the attenuated fibrosis in VOH versus POH. PMID:24018949

[Intrauterine intestinal volvulus].

PubMed

Gawrych, Elzbieta; Chojnacka, Hanna; Wegrzynowski, Jerzy; Rajewska, Justyna

2009-07-01

Intrauterine intestinal volvulus is an extremely rare case of acute congenital intestinal obstruction. The diagnosis is usually possible in the third trimester of a pregnancy. Fetal midgut volvulus is most likely to be recognized by observing a typical clockwise whirlpool sign during color Doppler investigation. Multiple dilated intestinal loops with fluid levels are usually visible during the antenatal ultrasound as well. Physical and radiographic findings in the newborn indicate intestinal obstruction and an emergency surgery is required. The authors describe intrauterine volvulus in 3 female newborns in which surgical treatment was individualized. The decision about primary or delayed anastomosis after resection of the gangrenous part of the small bowel was made at the time of the surgery and depended on the general condition of the newborn, as well as presence or absence of meconium peritonitis. Double loop jejunostomy was performed in case of two newborns, followed by a delayed end-to-end anastomosis. In case of the third newborn, good blood supply of the small intestine after untwisting and 0.25% lignocaine injections into mesentery led to the assumption that the torsion was not complete and ischemia was reversible. In the two cases of incomplete rotation the cecum was sutured to the left abdominal wall to prevent further twisting. The postoperative course was uneventful and oral alimentation caused no problems. Physical development of all these children has been normal (current age: 1-2 years) and the parents have not observed any disorders or problems regarding passage of food through the alimentary canal. Prompt antenatal diagnosis of this surgical emergency and adequate choice of intervention may greatly reduce mortality due to intrauterine volvulus.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

Mucosal Immunity and acute viral gastroenteritis

PubMed Central

Rose, Markus A

2014-01-01

Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq® and Rotarix® are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants’ acute gastroenteritis. PMID:25424826

An unexpected cause of small bowel obstruction in an adult patient: midgut volvulus

PubMed Central

Söker, Gökhan; Yılmaz, Cengiz; Karateke, Faruk; Gülek, Bozkurt

2014-01-01

The most important complication of intestinal malrotation is midgut volvulus because it may lead to intestinal ischaemia and necrosis. A 29-year-old male patient was admitted to the emergency department with abdominal pain. Ultrasonography (US), colour Doppler ultrasonography (CDUS), CT and barium studies were carried out. On US and CDUS, twisting of intestinal segments around the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and alteration of the SMA–SMV relationship were detected. CT demonstrated that the small intestine was making a rotation around the SMA and SMV, which amounted to more than 360°. The upper gastrointestinal barium series revealed a corkscrew appearance of the duodenum and proximal jejunum, which is a pathognomonic finding of midgut volvulus. Prior knowledge of characteristic imaging findings of midgut volvulus is essential in order to reach proper diagnosis and establish proper treatment before the development of intestinal ischaemia and necrosis. PMID:24811563

Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

PubMed

Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Surgical results of leg amputation according to Ghormley's technique in the treatment of chronic lower limb ischaemia.

PubMed

Wasiak, K; Paczkowski, P M; Garlicki, J M

2006-01-01

The authors present their experience in the treatment of chronic lower limb ischaemia resulting from atherosclerosis by below knee amputation according to Ghormley's technique, with the immediate application of a semi-rigid plaster cast and early rehabilitation. From a group of 664 patients requiring major amputations, 61 patients (52 men) aged 64 +/- 11 fulfilled the criteria for unilateral below-knee amputation for critical limb ischaemia for atherosclerosis consequences. Peri-operative (30-days) mortality was of 3.28%. Stump healing was very good or good (no need for further surgery) in over 2/3 of patients, but in 20% the need for above-knee amputation developed. Postoperative knee contracture (defined as 15 degrees or more limitation to the movement range) was observed in 11.5% of patients.

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

PubMed Central

Feng, Yongjia; Barrett, Meredith; Hou, Yue; Yoon, Hong Keun; Ochi, Takanori

2015-01-01

Feeding strategies to care for patients who transition from enteral nutrient deprivation while on total parenteral nutrition (TPN) to enteral feedings generally proceed to full enteral nutrition once the gastrointestinal tract recovers; however, an increasing body of literature suggests that a subgroup of patients may actually develop an increased incidence of adverse events, including death. To examine this further, we studied the effects of acute refeeding in a mouse model of TPN. Interestingly, refeeding led to some beneficial effects, including prevention in the decline in intestinal epithelial cell (IEC) proliferation. However, refeeding led to a significant increase in mucosal expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), as well as an upregulation in Toll-like receptor 4 (TLR-4). Refeeding also failed to prevent TPN-associated increases in IEC apoptosis, loss of epithelial barrier function, and failure of the leucine-rich repeat-containing G protein-coupled receptor 5-positive stem cell expression. Transitioning from TPN to enteral feedings led to a partial restoration of the small bowel microbial population. In conclusion, while acute refeeding led to some restoration of normal gastrointestinal physiology, enteral refeeding led to a significant increase in mucosal inflammatory markers and may suggest alternative strategies to enteral refeeding should be considered. PMID:26635320

Effects of oral administration of different doses of purified micronized flavonoid fraction on microvascular reactivity after ischaemia/reperfusion in the hamster cheek pouch

PubMed Central

Bouskela, E; Cyrino, F Z G A; Lerond, L

1997-01-01

The effects of a purified micronized flavonoid fraction (S5682) on mean internal diameter and blood flow of arterioles and venules, as well as the functional capillary density (FCD) were evaluated in the hamster cheek pouch microvasculature before and after 90 min of total ischaemia. Male hamsters were treated for ten days, twice a day, with oral doses of S5682 (5, 20, 80 and 160 mg kg−1 day−1) or placebo (10% lactose solution). The cheek pouch preparation was placed under an intravital microscope coupled to a closed circuit TV system. Local ischaemia was obtained by a cuff mounted around the neck of the everted pouch where it leaves the mouth of the hamster. Measurements were performed before ischaemia, at the onset of reperfusion and 10, 20, 30, 45 and 60 min thereafter. Diameters were measured by means of an image shearing device. Red blood cell (RBC) velocity was analysed by use of the dual-slit photometric technique. Blood flow was calculated from diameters and RBC velocities. FCD, defined as the number of capillaries with flowing blood per field of observation, was also assessed. During reperfusion, placebo-treated animals showed a significant vasodilatation, a decrease in blood flow and FCD and S5682-treated animals showed a clear trend, dose-dependent, towards maintaining these parameters closer to the value found before ischaemia. In conclusion, our results indicate that S5682 improves the microvascular reactivity and FCD after ischaemia/reperfusion. These data suggest that S5682 could function as an antioxidant, which may explain its beneficial therapeutic effect in chronic venous insufficiency where oxidative stress is involved in the pathological mechanism. PMID:9422805

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis. Results of a controlled clinical trial of selective decontamination.

PubMed

Luiten, E J; Hop, W C; Endtz, H P; Bruining, H A

1998-05-01

To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. Surgical intensive care units of 16 hospitals. A total of 2,159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patients) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73%) these infections occurred within 1 week following

[Intestinal perforation due to multiple magnet ingestion: a case report].

PubMed

Cevizci, Mehmet Nuri; Karadağ, Cetin Ali; Demir, Mesut; Dokucu, Ali Ihsan

2012-03-01

Multiple magnet ingestion during childhood may result in emergency situations. A single magnet may be discharged with intestinal peristalsis, but multiple magnets may stick together and cause significant intestinal complications. Here we present a case with intestinal perforation due to ingestion of multiple magnets and metal pieces. An eight-year-old girl presented with abdominal pain and vomiting. She had abdominal tenderness and defense on the physical examination. Abdominal X-ray showed air and fluid levels. Metallic images were not considered at first as important in the diagnosis. Abdominal ultrasonography was reported as acute appendicitis. During the abdominal exploration, the appendix was normal, but there were dense adherences around the ileum and cecum. After adhesiolysis, intestinal perforations were seen in the cecum and 15 and 45 cm proximal to the cecum. Magnet and metal pieces were present in the perforated segments. Wedge resection and primary repair was performed. There were no postoperative complications, and she was discharged on the postoperative fifth day. Pediatric surgeons should be aware of the complications of multiple magnet ingestion. If the patient has a history of multiple magnet ingestion, follow-up with daily abdominal X-rays should be done, and in cases where magnets seem to cluster together or if acute abdominal signs develop, surgical exploration should be considered.

[Acute liver ischaemia after gastro-oesophageal variceal bleeding].

PubMed

Senosiain Lalastra, Carla; Arribas Anta, Julia; Moreira Vicente, Víctor; Martínez González, Javier; Maroto Castellanos, Maite; García Sánchez, María Concepción; Zaera de la Fuente, Celia; López Durán, Sergio; Cañete Ruiz, Ángel; Albillos Martínez, Agustín

2016-11-01

Variceal upper gastrointestinal bleeding (UGIB) can trigger acute hypoxic hepatitis (AHH). The aim of this study was to analyse the incidence, associated risk factors and mortality of AHH after variceal UGIB. Retrospective study of cirrhotic patients with variceal UGIB, classified into 2 groups according to the development of AHH. AHH was diagnosed when AST and ALT reached levels 10 times above the upper limit of normal, after ruling out other causes of hepatitis. The standard initial treatment consisted of haemodynamic support, emergency endoscopy with rubber band ligation, somatostatin and antibiotics. In the case of failure of primary haemostasis, a transjugular intrahepatic portosystemic shunt (TIPS) was implanted. Both groups (AHH and non-AHH) were compared. Sixty-eight cirrhotic patients with variceal UGIB admitted to the gastroenterology department of Hospital Ramón y Cajal between January 2007 and March 2012 were analysed. Eleven of these patients (16.2%) developed AHH. Univariate analysis showed the following items as risk factors: diabetes (OR: 7.5; CI: 1.9-29), shock (OR: 8.5; CI: 2.06-34) and persistent bleeding (OR: 9.0, CI: 1.6-49, P=.03). However, multivariate analysis confirmed only diabetes (OR: 8.61; CI: 1.4-52.5) and shock (OR: 7.58; CI: 1.26-45.51) as risk factors. Mortality rate in the AHH group was 45%, compared to 10.5% in the non-HAA group (P=.012). AHH after variceal UGIB occurred in 16.2% of cirrhotic patients and was associated with a poorer prognosis, with a mortality rate of 45%. Our findings suggest that diabetes and shock are risk factors for the development of AHH. Early identification of at-risk patients could therefore help prevent AHH. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

PubMed

Wijnen, M H W A; Roumen, R M H; Vader, H L; Goris, R J A

2002-06-01

open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation. Copyright 2002 Elsevier Science Ltd.

Abdominal aortic occlusion and vascular compromise secondary to acute gastric dilatation in a patient with bulimia

PubMed Central

Doulias, T; Aljundi, W; Balchandra, S

2014-01-01

Acute gastric dilation is a rare but recognised complication in patients with bulimia and anorexia following binge episodes owing to decreased bowel motility. We present a rare case of acute gastric dilation secondary to bulimia in an otherwise healthy 18-year-old female patient that resulted in compression and complete occlusion of the abdominal aorta, leading to acute mesenteric and bilateral lower limb ischaemia. This resolved immediately following a laparotomy and gastric decompression. Management of these patients is very challenging owing to the lack of a successful precedent. To our knowledge, such a catastrophic complication has only ever been reported once in the literature and the outcome was fatal. Our case is of additional importance as it offers a successful management strategy for these patients. PMID:25350169

Abdominal aortic occlusion and vascular compromise secondary to acute gastric dilatation in a patient with bulimia.

PubMed

Elsharif, M; Doulias, T; Aljundi, W; Balchandra, S

2014-11-01

Acute gastric dilation is a rare but recognised complication in patients with bulimia and anorexia following binge episodes owing to decreased bowel motility. We present a rare case of acute gastric dilation secondary to bulimia in an otherwise healthy 18-year-old female patient that resulted in compression and complete occlusion of the abdominal aorta, leading to acute mesenteric and bilateral lower limb ischaemia. This resolved immediately following a laparotomy and gastric decompression. Management of these patients is very challenging owing to the lack of a successful precedent. To our knowledge, such a catastrophic complication has only ever been reported once in the literature and the outcome was fatal. Our case is of additional importance as it offers a successful management strategy for these patients.

Protective agents used as additives in University of Wisconsin solution to promote protection against ischaemia-reperfusion injury in rat lung.

PubMed

Chiang, C H; Wu, K; Yu, C P; Perng, W C; Yan, H C; Wu, C P; Chang, D M; Hsu, K

1998-09-01

1. An intervention to reduce ischaemia-reperfusion lung injury will be an important advance in transplant medicine. Although the mechanisms associated with producing ischaemia-reperfusion endothelial injury have not been completely elucidated, many of the injury mediators have been studied in detail. While no single pharmacological therapy is likely to be totally effective in eliminating this complex injury, we have developed a mixture of agents that are known to block pathways involved in producing ischaemia-reperfusion-associated lung vascular injury.2. The present study modified University of Wisconsin solution (UW) by adding one of the protective agents prostaglandin E1 (PGE1), dexamethasone (Dex) or dibutyryl cAMP (Bt2-cAMP), or a combination of these, to the perfusate of rat lungs exposed to 4 h of cold ischaemia followed by 1 h of reperfusion. Nine modified UW solutions were studied: (1) UW+Dex, (2) UW+PGE1, (3) UW+Bt2-cAMP, (4) UW+Dexx3, (5) UW+PGE1x3, (6) UW+Bt2-cAMPx3, (7) UW+Dex+PGE1, (8) UW+Dex+Bt2-cAMP, (9) UW+PGE1+Bt2-cAMP. These solutions were utilized in individual experiments to assess haemodynamic changes, lung weight gain, the capillary filtration coefficient (Kfc) and pathology in all lungs.3. The results indicate that lung weight gain and Kfc values were significantly lower than with UW alone in groups 1, 2 and 3, which contained only one additional protective agent. In groups 4, 5 and 6, which contain three times the concentration of each protective agent, both Kfc and lung weight gain were similar to those measured in groups 1, 2 and 3, i.e. lungs were protected but the protection was not dose dependent. In groups 7, 8 and 9, which contained two protective agents, lung weight gain and Kfc were greatly reduced compared with UW alone. Histopathological studies showed similar decreases in the injury profiles of lungs.4. Although UW contains several antioxidant protective agents such as allopurinol and glutathione, it did not provide effective

Modern treatment of infection and ischaemia to reduce major amputation in the diabetic foot.

PubMed

Edmonds, Michael

2013-01-01

Diabetic patients suffer a high rate of amputation. There are two main reasons; infection which can spread rapidly leading to overwhelming tissue destruction and severe peripheral arterial disease. Studies that have stratified patients according to the presence or absence of both peripheral arterial disease and infection have shown significantly worse outcomes in patients with both peripheral arterial disease and infection. There have been two crucial significant advances in diabetic foot care to improve the outlook of these diabetic patients. First, there has been the realisation that diabetic foot patients experience repeated crises from the rapid onset infection and need a special form of easily accessible care within a multidisciplinary diabetic foot service to provide prompt treatment of infection before it progresses to necrosis. Secondly, within such a service, prompt diagnosis of ischaemia and urgent revascularisation has been established as a further important aspect of successful management. The critical factor in saving limbs is making a rapid diagnosis of infection and ischaemia and administering the appropriate treatment early. In this way speedy healing can be achieved and this can prevent patients from needing amputations.

[Management of coronary artery disease in diabetic patients with lower limb critical ischaemia: assessment of operational risk, drug therapy and indications for interventions].

PubMed

Dedov, I I; Kalashnikov, V Iu; Terekhin, S A; Melkozerov, K V

2012-01-01

Despite obvious progress in management of diabetes mellitus, the DM-related complications rate remains inadmissibly high. Macroangiopathy is known to rank first amongst complications of diabetes mellitus, and coronary artery disease remains to be the major cause of death. Analysed herein are peculiarities of the clinical course in diabetic patients presenting with coronary artery disease and lower limb critical ischaemia, followed by discussing the issues concerning drug therapy, preoperative examination, and methods of diagnosis in this cohort of patients prior to vascular operations, assessment of the preoperative risk, indications for coronarography and myocardial revascularization. Also presented are the results of the main clinical trials dedicated to preoperative myocardial revascularization, including those in diabetic patients with limb critical ischaemia, and finally highlighting current importance of optimizing approaches to managing and working out algorithms of treatment policy for diabetic patients with a combination of coronary artery disease, diabetes mellitus, and critical limb ischaemia.

[Pathomorphological peculiarities of hemomicrocirculatory bed of the small and large intestine in acute peritonitis].

PubMed

Siplivyĭ, V A; Grinchenko, S V; Gorgol', N I; Dotsenko, V V; Evtushenko, A V

2014-01-01

Experimental comparative morphological investigation of hemomicrocirculation bed (HMCB) of the small and large bowel wall was performed in dynamics of an acute serous peritonitis. Spreaded aseptic peritonitis was simulated using injection of 5 ml of gamma-caraginen (Sigma, USA) in 1 ml of isotonic solution of sodium chloride. On the early stage of peritonitis (in 12 h from beginning of the experiment) in mucosa of small bowel nonsignificant venuls dilatation and the capillary lumen reduction were observed. In 1 day (reactive stage of peritonitis) in mucosa the quantity of capillars have had reduced significantly, comparing with such observed previously. On the 2-nd day (toxic stage of peritonitis) some capillary dilatation in intestinal villi and crypts coexistant with the blood rheology disorders in a form of stasis, change in permeability of the vessels walls, predominantly of the venous, was noted. On the 3-d day (late stage) the arteriol's spasm have had reduced, capillary paralytic dilatation was revealed. The staged course of experimental peritonitis with the HMCB changes, characteristic for every stage, was confirmed, basing on analysis of the investigation result.

Paroxysmal dyskinesia as an unusual and only presentation of subcortical white matter ischaemia: a report of two cases.

PubMed

Norlinah, M I; Shahizon, A M M

2008-12-01

Secondary paroxysmal dyskinesias (PxD) have been previously reported in patients with multiple sclerosis, lacunar infarcts, head trauma, metabolic disorders such as hyperglycaemia, hypocalcaemia, migraine and central nervous system (CNS) infections. The causative lesions typically involve the basal ganglia structures, medulla and rarely the spinal cord. We report two patients who presented with paroxysmal dyskinesias as the only manifestation of subcortical white-matter ischaemia. Patient 1 presented with 3-year history of paroxysmal kinesigenic dyskinesia (PKD) and patient 2 with 6-month history of paroxysmal nonkinesigenic dyskinesia (PNKD). All investigations, including CSF oligoclonal bands were negative, except for a brain MRI which showed multiple, non-enhancing subcortical white matter lacunar infarcts. Therefore, subcortical white matter ischaemia should also be included in the differential diagnosis of PxD.

Kawasaki Disease Presenting as Acute Intestinal Obstruction

PubMed Central

Lone, Yasir Ahmad; Menon, Jagadeesh; Menon, Prema; Vaiphei, Kim; Narasimha Rao, Katragadda Lakshmi; Thapa, Baburam; Gupta, Kirti

2017-01-01

Kawasaki disease (KD) is an acute febrile illness of childhood associated with vasculitis of medium-sized arteries especially the coronary arteries. Typical clinical features involving the skin, mucous surfaces, etc., occur sequentially over a few days. We report a rare presentation of KD as a surgical abdomen in a 2-year-old boy. Awareness of this presentation is important as it can otherwise lead to a delay in starting potentially life-saving intervention like intravenous immunoglobulins for cardiac complications kept cryptic by the manifest acute abdomen. PMID:28694577

Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

PubMed

Mulder, Gemma M; Nijboer, Willemijn N; Seelen, Marc A; Sandovici, Maria; Bos, Eelke M; Melenhorst, Wynand B W H; Trzpis, Monika; Kloosterhuis, Niels J; Visser, Lydia; Henning, Rob H; Leuvenink, Henri G D; Ploeg, Rutger J; Sunnarborg, Susan W; van Goor, Harry

2010-06-01

The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial.

PubMed

Beelen, D W; Elmaagacli, A; Müller, K D; Hirche, H; Schaefer, U W

1999-05-15

In a single-center open-label prospective study, a total of 134 marrow transplant recipients with hematologic malignancies were randomly assigned to a bacterial decontamination medication using metronidazole and ciprofloxacin (n = 68) or ciprofloxacin alone (n = 66) during 5 weeks posttransplant. The development of grades II to IV acute graft-versus-host disease (GVHD) was defined as the primary study endpoint. According to the intention-to-treat, 17 patients (25%) randomized to the combined decontamination medication and 33 patients (50%) randomized to ciprofloxacin alone developed grades II to IV GVHD (P <.002). The higher frequency of grades II to IV acute GVHD in patients randomized to ciprofloxacin alone resulted from a more than twofold increased number of patients developing liver or intestinal involvement with acute GVHD compared with patients randomized to the combined decontamination medication (P <.003). The influence of the study medication on grades II to IV acute GVHD was significant only in recipients of transplants from genotypically HLA-identical sibling donors (n = 80), whereas in recipients of transplants from donors other than HLA-identical siblings (n = 54), grades II to IV acute GVHD frequencies between the study arms were not significantly different. The combined decontamination was associated with a significant reduction of culture growth of intestinal anaerobic bacteria during 5 weeks posttransplant (P <. 00001). In addition, the number of cultures with growth of anaerobic bacteria (P <.005) as well as the median concentrations of anaerobic bacteria in the posttransplant period (P <.0001) were higher in patients contracting grades II to IV acute GVHD. Neither chronic GVHD nor overall survival was significantly different between the two study arms. In patients with HLA-identical sibling donors who were treated in early disease stages, the 5-year survival estimate was slightly, but not significant, higher after the combined decontamination

TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

PubMed

Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke

2009-08-14

Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

TLR2 Mediates Gap Junctional Intercellular Communication through Connexin-43 in Intestinal Epithelial Barrier Injury*

PubMed Central

Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K.; Cario, Elke

2009-01-01

Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1α-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair. PMID:19528242

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs.

PubMed

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P; Andreka, Peter

2007-06-01

Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

PubMed

Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

2018-05-04

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

PubMed

Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

2016-10-01

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

PubMed

Wan, Mei-Hua; Li, Juan; Tang, Wen-Fu; Gong, Han-Lin; Chen, Guang-Yuan; Xue, Ping; Zhao, Xian-Lin; Xia, Qing

2011-09-01

To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P < 0.05). The ANP rats treated with DCQT had lower wet to dry weight ratio, and milder myeloperoxidase activity and histopathology changes in pancreas and lung than those treated with saline (P < 0.05). Higher pressure of oxygen (PO2) was found in the rats treated with DCQT, while no difference in PCO2 was found between the DCQT and ANP groups (P > 0.05). Only two rats in the ANP group died. DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study12

PubMed Central

van Vliet, Sara J; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; van Rheenen, Patrick F

2016-01-01

Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM. Design: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6–59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling. Results: Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443–535 mg/kg feces) compared with 698 mg/kg feces (1438–244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112–22 ng/mL) compared with 2036 ng/mL (5800–149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831–131 ng/mL) compared with 3174 ng/mL (5819–357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation. Conclusions: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of

Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets

PubMed Central

Li, Jihong; Uzal, Francisco A.; McClane, Bruce A.

2016-01-01

Clostridium perfringens is a major cause of histotoxic and intestinal infections of humans and other animals. This Gram-positive anaerobic bacterium can produce up to three sialidases named NanH, NanI, and NanJ. The role of sialidases in histotoxic infections, such as gas gangrene (clostridial myonecrosis), remains equivocal. However, recent in vitro studies suggest that NanI may contribute to intestinal virulence by upregulating production of some toxins associated with intestinal infection, increasing the binding and activity of some of those toxins, and enhancing adherence of C. perfringens to intestinal cells. Possible contributions of NanI to intestinal colonization are further supported by observations that the C. perfringens strains causing acute food poisoning in humans often lack the nanI gene, while other C. perfringens strains causing chronic intestinal infections in humans usually carry a nanI gene. Certain sialidase inhibitors have been shown to block NanI activity and reduce C. perfringens adherence to cultured enterocyte-like cells, opening the possibility that sialidase inhibitors could be useful therapeutics against C. perfringens intestinal infections. These initial in vitro observations should be tested for their in vivo significance using animal models of intestinal infections. PMID:27869757

Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets.

PubMed

Li, Jihong; Uzal, Francisco A; McClane, Bruce A

2016-11-19

Clostridium perfringens is a major cause of histotoxic and intestinal infections of humans and other animals. This Gram-positive anaerobic bacterium can produce up to three sialidases named NanH, NanI, and NanJ. The role of sialidases in histotoxic infections, such as gas gangrene (clostridial myonecrosis), remains equivocal. However, recent in vitro studies suggest that NanI may contribute to intestinal virulence by upregulating production of some toxins associated with intestinal infection, increasing the binding and activity of some of those toxins, and enhancing adherence of C. perfringens to intestinal cells. Possible contributions of NanI to intestinal colonization are further supported by observations that the C. perfringens strains causing acute food poisoning in humans often lack the nanI gene, while other C. perfringens strains causing chronic intestinal infections in humans usually carry a nanI gene. Certain sialidase inhibitors have been shown to block NanI activity and reduce C. perfringens adherence to cultured enterocyte-like cells, opening the possibility that sialidase inhibitors could be useful therapeutics against C. perfringens intestinal infections. These initial in vitro observations should be tested for their in vivo significance using animal models of intestinal infections.

Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion

PubMed Central

Pride, Christelle Kamga; Mo, Li; Quesnelle, Kelly; Dagda, Ruben K.; Murillo, Daniel; Geary, Lisa; Corey, Catherine; Portella, Rafael; Zharikov, Sergey; St Croix, Claudette; Maniar, Salony; Chu, Charleen T.; K. H. Khoo, Nicholas; Shiva, Sruti

2014-01-01

Aims Nitrite (NO2–), a dietary constituent and nitric oxide (NO) oxidation product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number of animal models when administered during ischaemia or as a pre-conditioning agent hours to days prior to the ischaemic episode. When present during ischaemia, the reduction of nitrite to bioactive NO by deoxygenated haem proteins accounts for its protective effects. However, the mechanism of nitrite-induced pre-conditioning, a normoxic response which does not appear to require reduction of nitrite to NO, remains unexplored. Methods and results Using a model of hypoxia/reoxygenation (H/R) in cultured rat H9c2 cardiomyocytes, we demonstrate that a transient (30 min) normoxic nitrite treatment significantly attenuates cell death after a hypoxic episode initiated 1 h later. Mechanistically, this protection depends on the activation of protein kinase A, which phosphorylates and inhibits dynamin-related protein 1, the predominant regulator of mitochondrial fission. This results morphologically, in the promotion of mitochondrial fusion and functionally in the augmentation of mitochondrial membrane potential and superoxide production. We identify AMP kinase (AMPK) as a downstream target of the mitochondrial reactive oxygen species (ROS) generated and show that its oxidation and subsequent phosphorylation are essential for cytoprotection, as scavenging of ROS prevents AMPK activation and inhibits nitrite-mediated protection after H/R. The protein kinase A-dependent protection mediated by nitrite is reproduced in an intact isolated rat heart model of I/R. Conclusions These data are the first to demonstrate nitrite-dependent normoxic modulation of both mitochondrial morphology and function and reveal a novel signalling pathway responsible for nitrite-mediated cardioprotection. PMID:24081164

The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

NASA Astrophysics Data System (ADS)

Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

2007-07-01

It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

Short intra-aortic balloon pump in a swine model of myocardial ischaemia: a proof-of-concept study.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-03-01

This proof-of-concept study examined the haemodynamic performance as well as the coronary and visceral organ perfusion using a new short balloon for intra-aortic counterpulsation (IABP) in a swine model of myocardial ischaemia. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned into 3 groups undergoing IABP implantation with a 35-ml short balloon (n = 6), a 40-ml short balloon (n = 6) or no IABP implantation (controls, n = 6). Haemodynamics, and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric and renal flows increased significantly at tR1 only in the IABP groups (all, P < 0.001) and were significantly higher than controls throughout the reperfusion periods (P < 0.001). Coronary systolic and diastolic blood flows increased only at tR1 in the IABP groups (all, P < 0.001) but were higher than controls at tR1-tR6. The IABP was associated with enhanced haemodynamics compared with controls. No difference was detected using different balloon volumes (all, P > 0.05). The new short balloon significantly increased visceral flow, enhanced haemodynamics and improved coronary circulation during reperfusion following myocardial ischaemia in our experimental model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Visualisation of exercise-induced ischaemia of the right ventricle by thallium-201 single photon emission computed tomography.

PubMed Central

Chiba, J.; Takeishi, Y.; Abe, S.; Tomoike, H.

1997-01-01

OBJECTIVE: Exercise thallium-201 (201T1) single photon emission computed tomography (SPECT) has been used to detect potential ischaemia in the left ventricular myocardium but not in the right ventricle. The purpose of this study was to establish the clinical usefulness of a right ventricular polar map of 201T1 SPECT for visualisation of exercise-induced right ventricular ischaemia. METHODS: Myocardial 201T1 SPECT was obtained immediately after treadmill exercise in 97 patients with suspected coronary artery disease. A region of interest was placed over the right ventricle (RV) on post-stress transaxial images. Short axis images of this region were generated and reconstructed as a bull's eye polar map. Normal ranges of RV 201T1 uptake were determined in 12 patients with normal coronary arteries. Scintigraphic criteria for identifying RV perfusion abnormality were derived from 25 patients with right coronary artery (RCA) stenosis greater than 75%. These criteria were applied to 60 consecutive patients with suspected coronary artery disease. RESULTS: Perfusion defects in the RV were larger in patients with proximal RCA stenosis than in those with distal RCA stenosis (mean (SD) 28 (16)% v 6 (5)%, P < 0.001). The sensitivity and specificity of the RV polar map for the detection of proximal RCA stenosis were 67% (8/12) and 98% (47/48), respectively. RV perfusion defects became undetectable in 9 patients who had successful percutaneous transluminal coronary angioplasty to a proximal RCA lesion. CONCLUSIONS: A right ventricular polar map display was useful for visualising exercise-induced right ventricular ischaemia. Images PMID:9038692

Reduced Triglyceride Secretion in Response to an Acute Dietary Fat Challenge in Obese Compared to Lean Mice

PubMed Central

Uchida, Aki; Whitsitt, Mary C.; Eustaquio, Trisha; Slipchenko, Mikhail N.; Leary, James F.; Cheng, Ji-Xin; Buhman, Kimberly K.

2012-01-01

Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6 h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice. PMID:22375122

IL-21 promotes myocardial ischaemia/reperfusion injury through the modulation of neutrophil infiltration.

PubMed

Wang, Kejing; Wen, Shuang; Jiao, Jiao; Tang, Tingting; Zhao, Xin; Zhang, Min; Lv, Bingjie; Lu, Yuzhi; Zhou, Xingdi; Li, Jingyong; Nie, Shaofang; Liao, Yuhua; Wang, Qing; Tu, Xin; Mallat, Ziad; Xia, Ni; Cheng, Xiang

2018-04-01

The immune system plays an important role in driving the acute inflammatory response following myocardial ischaemia/reperfusion injury (MIRI). IL-21 is a pleiotropic cytokine with multiple immunomodulatory effects, but its role in MIRI is not known. Myocardial injury, neutrophil infiltration and the expression of neutrophil chemokines KC (CXCL1) and MIP-2 (CXCL2) were studied in a mouse model of MIRI. Effects of IL-21 on the expression of KC and MIP-2 in neonatal mouse cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were determined by real-time PCR and ELISA. The signalling mechanisms underlying these effects were explored by western blot analysis. IL-21 was elevated within the acute phase of murine MIRI. Neutralization of IL-21 attenuated myocardial injury, as illustrated by reduced infarct size, decreased cardiac troponin T levels and improved cardiac function, whereas exogenous IL-21 administration exerted opposite effects. IL-21 increased the infiltration of neutrophils and increased the expression of KC and MIP-2 in myocardial tissue following MIRI. Moreover, neutrophil depletion attenuated the IL-21-induced myocardial injury. Mechanistically, IL-21 increased the production of KC and MIP-2 in neonatal CMs and CFs, and enhanced neutrophil migration, as revealed by the migration assay. Furthermore, we demonstrated that this IL-21-mediated increase in chemokine expression involved the activation of Akt/NF-κB signalling in CMs and p38 MAPK/NF-κB signalling in CFs. Our data provide novel evidence that IL-21 plays a pathogenic role in MIRI, most likely by promoting cardiac neutrophil infiltration. Therefore, targeting IL-21 may have therapeutic potential as a treatment for MIRI. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

VEGF released from a fibrin biomatrix increases VEGFR-2 expression and improves early outcome after ischaemia-reperfusion injury.

PubMed

Moritz, Martina; Pfeifer, Sabine; Balmayor, Elizabeth R; Mittermayr, Rainer; Wolbank, Susanne; Redl, Heinz; van Griensven, Martijn

2017-07-01

Skeletal ischaemia-reperfusion (I-R) injury may influence patient outcome after severe vascular trauma or clamping of major vessels. The aim of this study was to observe whether locally applied vascular endothelial growth factor (VEGF) in fibrin could induce the expression of VEGF-receptor-2 (VEGFR-2) and improve the outcome after I-R injury. Transgenic mice expressing VEGFR-2 promoter-controlled luciferase were used for the assessment of VEGFR-2 expression. Ischaemia was induced for 2 h by a tension-controlled tourniquet to the hind limb, followed by 24 h of reperfusion. The animals were locally injected subcutaneously with fibrin sealant containing 20 or 200 ng VEGF; control animals received no treatment or fibrin sealant application. In vivo VEGFR-2 expression was quantified upon administration of luciferin at several observation times. For oedema and inflammation quantification, wet:dry ratio measurements and a myeloperoxidase assay of the muscle tissue were performed. Laser Doppler imaging showed that ischaemia was present and that the blood flow had returned to baseline levels after 24 h of reperfusion. VEGFR-2 expression levels in the fibrin + 200 ng VEGF were significantly higher than in all other groups. Granulocyte infiltration was reduced in both treatment groups, as well as reduced oedema formation. These results showed that VEGF released from fibrin had a positive effect on early I-R outcome in a mouse model, possibly via VEGFR-2. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Time-course evaluation of intestinal structural disorders in a porcine model of intra-abdominal hypertension by mechanical intestinal obstruction

PubMed Central

Sánchez-Margallo, Francisco M.; Candanosa-Aranda, Irma Eugenia; Malbrain, Manu L. N. G.; Wise, Robert

2018-01-01

Background A mechanical intestinal obstruction (MIO) can generate intraabdominal hypertension (IAH) that is life threatening. The intestines are very sensitive to IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis and bacterial translocations. This may lead to acute intestinal distress syndrome (AIDS). The identification of intestinal injuries during IAH and its correlation with clinical parameters as the abdominal perfusion pressure (APP), the gastric intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to evaluate the sequence of intestinal histopathological findings in an MIO model and to analyze potential relationships with parameters currently used in clinical practice (APP, pHi and Lc). Material and methods Twenty pigs were divided into three groups: a control group (n = 5) and two experimental groups with 20 mmHg (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every 30 minutes in all groups. The intestinal damage was graded according to the Park Score. Results Intestinal injuries were found in 42.9% of pigs in the experimental groups. The lesions were independent of the level and duration of IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and G2, there were no significant differences among those uninjured (I-). Lc was significantly increased in all I+ pigs from the onset of IAH. Conclusion The IAH by MIO causes intestinal lesions from the first 30 minutes with concurrent decreases in APP and pHi and increases in Lc. Lc could be the best clinical parameter related to intestinal damages with a clear difference between I + and I- animals. PMID:29357386

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

PubMed

Li, Guang-hui; Wang, Dong-lin; Hu, Yi-de; Pu, Ping; Li, De-zhi; Wang, Wei-dong; Zhu, Bo; Hao, Ping; Wang, Jun; Xu, Xian-qiong; Wan, Jiu-qing; Zhou, Yi-bing; Chen, Zheng-tang

2010-09-01

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs

PubMed Central

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P

2007-01-01

Background Ischaemic preconditioning results in a reduction in ischaemic‐reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non‐vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. Objective To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Methods Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Results Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Conclusion Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential. PMID:17449499

Occurrence of small intestinal volvulus in a terrier puppy-a case report

PubMed Central

Golshahi, Hannaneh; Tavasoly, Abbas; Namjoo, Abdolrasol; Bahmani, Mahmoud

2014-01-01

Volvulus is the torsion of an organ around its root. In dogs, volvulus of the stomach is well known, but volvulus of the small intestine is rare. A dead 3-month-old female terrier puppy was presented for postmortem examination. According to owner statements, the puppy was depressed, lethargic and had abdominal pain, abdominal distension, severe diarrhea and vomiting a few hours before death. With gross and histopathologic studies, the death of this puppy was indorsed to small intestinal volvulus, subsequent infarction, peritonitis and likely acute toxaemia and/or septicaemia. The present case is going to be the first recorded case of small intestinal volvulus in dog in Iran.

[Effects of electro-acupuncture at Zusanli point on gastric and intestinal blood flow in rats with acute necrotizing pancreatitis].

PubMed

Bai, Lu; Zhu, Lin; Tang, Wen-Fu; Wan, Mei-Hua; Huang, Wei; Chen, Guang-Yuan

2013-11-01

To investigate the effects of electro-acupuncture (EA) at Zusanli point on gastric and intestinal blood flow and serum endothelin-1(ET-1), nitricoxide(NO), thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) in rats with acute necrotizing pancreatitis (ANP). Thirty-six male Sprague Dawley (SD) rats were randomly divided into sham operation (sham), ANP and EA groups (n = 12). ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreaticobiliary. EA was applied to Zusanli for 30 min at 2 h and 6 h after the operation in EA group. Gastric and intestinal mucosal blood flow was measured by laser doppler flowmetry (LDF) at 12 h and 24 h after operation, while the levels of serum ET-1, NO, TXB2 and 6-K-PGF1alpha were detected. The gastric and intestinal blood flow in ANP rats were significantly lower than those in the sham group (P < 0.05), but those of EA groups were higher than those in ANP groups (P < 0.05). The serum ET-1, NO and ET-1/NO levels in ANP group were increased when compared with SO group (P < 0.05). After the electro-acupuncture treatment at Zusanli point, the levels of ET-1, NO and ET-1/N were decreased, and there were significant differences of ET-1 (at 12 h, 24 h), NO (at 12 h) and ET-1/NO (at 24 h) between EA and ANP group (P < 0.05). The levels of serum TXB2, 6-K-PGF1alpha and TXB2/6-K-PGF1alpha in ANP group were also increased (P < 0.05), but those in EA group were decreased, and there were significant differences of TXB2 (at 12 h, 24 h), 6-K-PGF1alpha (at 12 h) and TXB2/6-K-PGF1alpha (at 24 h) compared with ANP groups (P < 0.05). Electro-acupuncture at Zusanli point can significantly improve the gastric and intestinal mucosa blood flow in ANP rats, which may be related to the regulation of serum ET-1, NO, TXB2, 6-K-PGF1alpha.

Acute caecal volvulus: A diagnostic paradigm.

PubMed

Chaudry, Tariq Hassan; Jamil, Munawar; Niaz, Khurram; Basher, Goher

2015-12-01

Acute Caecal Volvulus is a rare etiology in cases of Intestinal obstruction. We are presenting the data of 11 cases out of 1032 cases of intestinal obstruction between June 2008 to June 2013, who presented in the emergency department of Bahawal Victoria Hospital Bahawalpur. The mean age was 36±3.38 years with female preponderance in this retrospective study. The persistent distinctive features were chronic intermittent pain followed by the passage of flatus (54%), severe right lower quadrant colicky pain (31%) and abdominal distention (59%). Radiologically the dilated caecum with air fluid level (68%) was persistent finding with lateralization of small gut in few patients (12%). Cecopexy (18%), right Hemicolectomy with primary anastomosis (63.63%) and Ileostomy with mucous fistula (18%) were offered. Wound sepsis (27%) and chest infection (18%) were common sequele. Acute Caecal Volvulus diagnosis requires a heightened clinical suspicion on the basis of symptoms like RLQ pain/mass which is relieved by passage of flatus and early radiological assistance in all cases of intestinal obstruction.

Obturator hernia: a rare case of acute mechanical intestinal obstruction.

PubMed

Aydin, Ibrahim; Yucel, Ahmet Fikret; Pergel, Ahmet; Sahin, Dursun Ali

2013-01-01

Obturator hernia is a rare type of pelvic hernia which generally occurs in elderly patients with accompanying diseases. Because it is difficult to diagnose before surgery, the morbidity and mortality rates for obturator hernia are high. The most common symptom is strangulation combined with mechanical intestinal obstruction.

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

PubMed

Pucci Molineris, M; Gonzalez Polo, V; Perez, F; Ramisch, D; Rumbo, M; Gondolesi, G E; Meier, D

2018-04-01

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67 + IL-22R + stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R + Ki-67 + stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Protective effects of saizen in combination with stilamin on intestinal mucosa of a rabbit model of severe acute pancreatitis.

PubMed

Lu, Yan; Yu, Yanmei; Yang, Meilan; Liu, Hui; Li, Bin; Xu, Hongwei

2013-01-01

The objective of this study was to investigate whether the regimen of saizen, a recombinant human somatropin, in combination stilamin, a somatostatin analog, exerts synergistic effect on intestinal mucosa of a rabbit model of severe acute pancreatitis. The rabbits were randomly divided into 3 groups: group A without any treatment, group B with single treatment of stilamin, and group C with treatment of saizen combined with stilamin. The blood levels of D-lactate, insulinlike growth factor 1, prealbumin, and albumin were detected at the 6th, 12th, 24th, 48th, and 72nd hours after modeling. The pathological changes in terms of the villus height, crypt depth, and mucosal thickness were observed. The caspase 3 expression and apoptotic indices were evaluated. The blood levels of D-lactate at the 48th hour; insulinlike growth factor 1 at the 24th and 48th hours; prealbumin at the 24th, 48th, and 72nd hours; and albumin at the 48th hour in group C were significantly higher than these in the other 2 groups. Pathological changes in group C were slighter; the level of caspase 3 and apoptotic index in group C were significantly lower than those in the other 2 groups. The combination of saizen with stilamin can enhance intestinal mucosa barrier function.

Obturator Hernia: A Rare Case of Acute Mechanical Intestinal Obstruction

PubMed Central

Yucel, Ahmet Fikret; Pergel, Ahmet; Sahin, Dursun Ali

2013-01-01

Obturator hernia is a rare type of pelvic hernia which generally occurs in elderly patients with accompanying diseases. Because it is difficult to diagnose before surgery, the morbidity and mortality rates for obturator hernia are high. The most common symptom is strangulation combined with mechanical intestinal obstruction. PMID:23738179

Strongyloides stercoralis hyperinfection associated with impaired intestinal motility disorder

PubMed Central

Figueira, Cláudia Frangioia; Cos, Lynda Dorene; Ussami, Edson Yassushi; Otoch, José Pinhata; Felipe-Silva, Aloisio

2015-01-01

Infection by Strongyloides stercoralis is a highly prevalent helminthiasis, which is mostly distributed in the tropical and subtropical regions of the world. Although a substantial number of cases are asymptomatic or paucisymtomatic, severe and life-threatening forms of this infection still occur and not infrequently is lately diagnosed. Gram-negative bacteria septicemia, which frequently accompanies the severe helminthiasis, contributes to the high mortality rate. Severe infection is invariably triggered by any imbalance in the host's immunity, favoring the auto-infective cycle, which increases the intraluminal parasite burden enormously. Clinical presentation of severe cases is varied, and diagnosis requires a high suspicion index. Acute abdomen has been reported in association with S. stercoralis infection, but intestinal necrosis is rarely found during the surgical approach. The authors report the case of a man who sought the emergency unit with recent onset abdominal pain. Clinical and imaging features were consistent with obstructive acute abdomen. Scattered adhesions and a necrotic ileal segment with a tiny perforation represented the surgical findings. The patient outcome was unfavorable and respiratory distress required an open lung biopsy. Both surgical specimens showed S. stercoralis infection. Unfortunately the patient underwent multiple organ failure and septicemia, and subsequently died. The authors call attention to the finding of intestinal necrosis and impaired intestinal motility disorder as possibilities for the diagnosis and risk factor, respectively, for a severe infection of S. stercoralis. PMID:26484331

Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

PubMed

Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

2014-03-01

Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

Interactions of Giardia sp. with the intestinal barrier: Epithelium, mucus, and microbiota

PubMed Central

Amat, Christina B.; Buret, André G.

2017-01-01

ABSTRACT Understanding how intestinal enteropathogens cause acute and chronic alterations has direct animal and human health perspectives. Significant advances have been made on this field by studies focusing on the dynamic crosstalk between the intestinal protozoan parasite model Giardia duodenalis and the host intestinal mucosa. The concept of intestinal barrier function is of the highest importance in the context of many gastrointestinal diseases such as infectious enteritis, inflammatory bowel disease, and post-infectious gastrointestinal disorders. This crucial function relies on 3 biotic and abiotic components, first the commensal microbiota organized as a biofilm, then an overlaying mucus layer, and finally the tightly structured intestinal epithelium. Herein we review multiple strategies used by Giardia parasite to circumvent these 3 components. We will summarize what is known and discuss preliminary observations suggesting how such enteropathogen directly and/ or indirectly impairs commensal microbiota biofilm architecture, disrupts mucus layer and damages host epithelium physiology and survival. PMID:28452685

The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

PubMed Central

Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

2016-01-01

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

Electrocardiogram interpretation in general practice: relevance to prehospital thrombolysis.

PubMed Central

McCrea, W A; Saltissi, S

1993-01-01

OBJECTIVE--To assess, in the context of their possible role in prehospital thrombolysis, the ability of general practitioners to recognise acute transmural myocardial ischaemia/infarction on an electrocardiogram. DESIGN--150 doctors (every fifth name) were selected from the alphabetical list of 750 on Merseyside general practitioner register and without prior warning were asked to interpret a series of six 12 lead electrocardiograms. Three of these showed acute transmural ischaemia/infarction, one was normal, and two showed non-acute abnormalities. Details of doctors' ages, postgraduate training, and clinical practice were sought. SETTING--General practitioners' surgeries and postgraduate centres within the Merseyside area. PARTICIPANTS--106 general practitioners (mean age 45 years) agreed to participate. MAIN OUTCOME MEASURE--Accuracy of general practitioners' interpretations of the six electrocardiograms. RESULTS--82% of general practitioners correctly recognised a normal electrocardiogram. Recognition of acute abnormalities was less reliable. Between 33% and 61% correctly identified acute transmural ischaemia/infarction depending on the specific trace presented. Accurate localisation of the site of the infarct was achieved only by between 8% and 30% of participants, while between 22% and 25% correctly interpreted non-acute abnormalities. Neither routine use of electrocardiography nor postgraduate hospital experience in general medicine was associated with significantly greater expertise. CONCLUSION--The current level of proficiency of a sample of general practitioners in the Merseyside area in recognising acute transmural ischaemia/infarction on an electrocardiogram suggests that refresher training is needed if general practitioners are to give prehospital thrombolysis. Images PMID:8398491

Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats.

PubMed

Pirat, Arash; Zeyneloglu, Pinar; Aldemir, Derya; Yücel, Muammer; Ozen, Ozlem; Candan, Selim; Arslan, Gülnaz

2006-01-01

In this rat model study we evaluated whether pretreatment with simvastatin affects the severity of acute lung injury caused by intestinal ischemia-reperfusion (I/R). Twenty-four animals were randomly allocated to three equal groups (sham, control, simvastatin). The simvastatin group was pretreated with simvastatin 10 mg x kg(-1) x day(-1) for 3 days, whereas the other groups received placebo. The simvastatin and control groups underwent 60 min of superior mesenteric artery occlusion and 90 min of reperfusion. Compared with the simvastatin group, the control group exhibited significantly more severe intestinal I/R-induced acute lung injury, as indicated by lower Pao2 and oxygen saturation (P = 0.01 and P = 0.005, respectively) and higher mean values for neutrophil infiltration of the lungs (P = 0.003), total lung histopathologic injury score (P = 0.003), lung wet-to-dry weight ratio (P = 0.009), and lung-tissue malondialdehyde levels (P = 0.016). The control and simvastatin groups had similar serum levels and similar bronchoalveolar lavage fluid levels of cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and P-selectin at all measurements, except for a significantly higher level of bronchoalveolar lavage fluid P-selectin in the control group (P = 0.006). Pretreatment with simvastatin reduces the severity of acute lung injury induced by intestinal I/R in rats.

RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury.

PubMed

Cabrera-Fuentes, H A; Ruiz-Meana, M; Simsekyilmaz, S; Kostin, S; Inserte, J; Saffarzadeh, M; Galuska, S P; Vijayan, V; Barba, I; Barreto, G; Fischer, S; Lochnit, G; Ilinskaya, O N; Baumgart-Vogt, E; Böning, A; Lecour, S; Hausenloy, D J; Liehn, E A; Garcia-Dorado, D; Schlüter, K-D; Preissner, K T

2014-12-01

Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial "ischaemia/reperfusion (I/R) injury" remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracellular RNA (eRNA) and tumour-necrosis-factor α (TNF-α), may dictate I/R injury. In an experimental in vivo mouse model of myocardial I/R as well as in the isolated I/R Langendorff-perfused rat heart, cardiomyocyte death was induced by eRNA and TNF-α. Moreover, TNF-α promoted further eRNA release especially under hypoxia, feeding a vicious cell damaging cycle during I/R with the massive production of oxygen radicals, mitochondrial obstruction, decrease in antioxidant enzymes and decline of cardiomyocyte functions. The administration of RNase1 significantly decreased myocardial infarction in both experimental models. This regimen allowed the reduction in cytokine release, normalisation of antioxidant enzymes as well as preservation of cardiac tissue. Thus, RNase1 administration provides a novel therapeutic regimen to interfere with the adverse eRNA-TNF-α interplay and significantly reduces or prevents the pathological outcome of ischaemic heart disease.

Titanium Dioxide Nanoparticle Ingestion Alters Nutrient Absorption in an In Vitro Model of the Small Intestine

PubMed Central

Guo, Zhongyuan; Martucci, Nicole J.; Moreno-Olivas, Fabiola; Tako, Elad; Mahler, Gretchen J.

2017-01-01

Ingestion of titanium dioxide (TiO2) nanoparticles from products such as agricultural chemicals, processed food, and nutritional supplements is nearly unavoidable. The gastrointestinal tract serves as a critical interface between the body and the external environment, and is the site of essential nutrient absorption. The goal of this study was to examine the effects of ingesting the 30 nm TiO2 nanoparticles with an in vitro cell culture model of the small intestinal epithelium, and to determine how acute or chronic exposure to nano-TiO2 influences intestinal barrier function, reactive oxygen species generation, proinflammatory signaling, nutrient absorption (iron, zinc, fatty acids), and brush border membrane enzyme function (intestinal alkaline phosphatase). A Caco-2/HT29-MTX cell culture model was exposed to physiologically relevant doses of TiO2 nanoparticles for acute (four hours) or chronic (five days) time periods. Exposure to TiO2 nanoparticles significantly decreased intestinal barrier function following chronic exposure. Reactive oxygen species (ROS) generation, proinflammatory signaling, and intestinal alkaline phosphatase activity all showed increases in response to nano-TiO2. Iron, zinc, and fatty acid transport were significantly decreased following exposure to TiO2 nanoparticles. This is because nanoparticle exposure induced a decrease in absorptive microvilli in the intestinal epithelial cells. Nutrient transporter protein gene expression was also altered, suggesting that cells are working to regulate the transport mechanisms disturbed by nanoparticle ingestion. Overall, these results show that intestinal epithelial cells are affected at a functional level by physiologically relevant exposure to nanoparticles commonly ingested from food. PMID:28944308

[Volvolus in an adult patient due to intestinal malrotation. Case report and review of literature].

PubMed

Nardone, Armando; Tamini, Nicolò; Nespoli, Luca; Pirovano, Riccardo

2010-01-01

Intestinal malrotation is a rare cause of bowel obstruction in adults and it could create a perplexing situation for surgeons not familiar with this pediatric pathology. Symptomatic patients present either acutely with bowel obstruction and intestinal ischemia with a midgut or cecal volvolus, or chronically with vague abdominal pain. Several modalities can be used to describe the intestinal abnormality such as barium X-ray, computer tomography scans, angiography and sometimes also the explorative laparotomy. The authors report on a case 62 years-old women presented to Emergency Center for plurime episodies of biliar emesis and diffuse abdominal pain in the last 5 days and treated for bowel obstruction secondary to a midgut volvolus in anomaly of fetal intestinal rotation.

Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges

PubMed Central

Millar, Lancelot J.; Shi, Lei; Hoerder-Suabedissen, Anna; Molnár, Zoltán

2017-01-01

Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries. Recent investigations of the transient cortical layer known as subplate, especially regarding subplate’s secretory role, opens up a novel set of potential molecular modulators of neonatal HI injury. This review examines the biological mechanisms of human neonatal HI, discusses evidence for the relevance of subplate-secreted molecules to this condition, and evaluates available animal models. Neuroserpin, a neuronally released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post-ischaemic injury. PMID:28533743

Intestinal Microbiota at Engraftment Influence Acute Graft-Versus-Host Disease via the Treg/Th17 Balance in Allo-HSCT Recipients.

PubMed

Han, Lijie; Jin, Hua; Zhou, Lizhi; Zhang, Xin; Fan, Zhiping; Dai, Min; Lin, Qianyun; Huang, Fen; Xuan, Li; Zhang, Haiyan; Liu, Qifa

2018-01-01

Animal models have indicated that intestinal microbiota influence acute graft-versus-host disease (aGVHD) by modulating immune homeostasis. But, in humans, the mechanism by which the microbiota induces aGVHD remains unclear. In this study, we investigated the relationship between the intestinal microbiota and T cell subsets in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) to explore the mechanism by which microbiota induced aGVHD. Based on aGVHD, this study was categorized into two groups: grades II-IV aGVHD (aGVHD group, n  = 32) and grade 0-I aGVHD (non-aGVHD group, n  = 49). The intestinal microbiota was detected by 16S rRNA gene sequencing, and the T cell subsets and histone 3 (H3) acetylation in CD4+ T cells in the peripheral blood was assayed by flow cytometry at the time of engraftment. The aGVHD group had greater low microbial diversity than the non-aGVHD group (56.3 versus 24.5%, p  = 0.004). The bacterial community was depleted of Clostridia (e.g., the Lachnospiraceae and Ruminococcaceae families) and enriched for Gammaproteobacteria (e.g., the Enterobacteriaceae family) in the aGVHD group compared with the non-aGVHD group. The relative abundance of Lachnospiraceae and Ruminococcaceae was positively correlated with the Treg/Th17 ratio counts ( r  = 0.469 and 0.419; p  < 0.001 and <0.001, respectively), whereas Enterobacteriaceae was negatively correlated with the Treg/Th17 ratio ( r  = -0.277; p  = 0.012). The level of acetylated H3 in CD4+ T cells was not only correlated with Lachnospiraceae/Ruminococcaceae, but also with the Treg/Th17 ratio ( r  = 0.354; p  = 0.001). In conclusions, our results suggest that decreased Lachnospiraceae and Ruminococcaceae and increased Enterobacteriaceae, correlate with a Treg/Th17 imbalance, which might be through acetylated H3 in CD4+ T cells. These findings suggest that intestinal microbiota might induce aGVHD by influencing the Treg/Th17 balance.

[X-ray diagnostic of partial intestinal obstruction in small intestine diseases: a glance on the problem of radiologist-gastroenterologist].

PubMed

Levchenko, S V; Kotovshchikova, A A; Orlova, N V

2013-01-01

The article is devoted to special features of X-ray examining of patients suffering from acute abdomen pain and X-ray paradigma of some intestine diseases as a cause of partial bowel obstruction. Own clinical data are presented. Long-term experience of our X-ray department is summarized. The possibilities of X-ray examining of abdomen with and without contrast in patients with partial bowel obstruction are described.

Early glycogen synthase kinase-3β and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.

PubMed

Majd, Shohreh; Power, John H T; Koblar, Simon A; Grantham, Hugh J M

2016-08-01

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

PubMed Central

Faga, Teresa; Pisani, Antonio; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

Prospective, observational, cross-sectional study of intestinal infections among acutely active inflammatory bowel disease patients.

PubMed

Navarro-Llavat, Mercè; Domènech, Eugeni; Bernal, Isabel; Sánchez-Delgado, Jordi; Manterola, José M; Garcia-Planella, Esther; Mañosa, Míriam; Cabré, Eduard; Gassull, Miquel A

2009-01-01

Intestinal infections have been claimed to precipitate or aggravate flares of inflammatory bowel disease (IBD). The reported incidence of such infections among IBD patients varies between 9 and 13%, but only a few prospective studies have been conducted. To evaluate the incidence of intestinal infections by enteropathogens in patients with active IBD, their impact on clinical outcome, and to identify associated risk factors. Consecutive patients admitted because of a relapse or suspected onset of IBD were prospectively included. At admittance, stool samples for culture, examination for intestinal parasites, and cytotoxin assay for Clostridium difficile were collected. Baseline clinical characteristics, potential risk factors for gastrointestinal infections, and clinical outcome were recorded. Ninety-nine episodes were included. Six intestinal infections were diagnosed in 6 patients (5 ulcerative colitis, 1 ileocolonic Crohn's disease), Campylobacter jejuni being the most frequent isolated microbe (n = 5). None of the patients with intestinal infection needed surgery, but two of them required second-line therapies. Gastrointestinal infections among IBD patients do not exceed 10% and occur mostly in patients with extensive involvement of the colon. Infection by enteropathogenic bacteria does not appear to be associated with a poorer clinical outcome of the IBD flare. Copyright 2009 S. Karger AG, Basel.

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

PubMed

Rentea, Rebecca M; Lam, Vy; Biesterveld, Ben; Fredrich, Katherine M; Callison, Jennifer; Fish, Brian L; Baker, John E; Komorowski, Richard; Gourlay, David M; Otterson, Mary F

2016-10-01

Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome. Copyright © 2016 Elsevier Inc. All rights reserved.

Alleviation of ischaemia-reperfusion injury by endogenous estrogen involves maintaining Bcl-2 expression via the ERα signalling pathway.

PubMed

Zhang, Zeng-Li; Qin, Pei; Liu, Yuhong; Zhang, Li-Xia; Guo, Hang; Deng, You-Liang; Yizhao-Liu; Hou, Yu-Shu; Wang, Li-Yang; Miao, Yi; Ma, Yu-Long; Hou, Wu-Gang

2017-04-15

The neuroprotective effects of estrogen against cerebral ischaemia have been confirmed by multiple basic and clinical studies. However, most of these studies used exogenous estrogen administered via different injection methods, and the neuroprotective effects of endogenous estrogen produced by ovaries during different phases of estrous cycle and the underlying mechanisms involved have rarely been explored. In this study, we first identified the stage of estrous cycle via vaginal smears and then measured serum estradiol levels at each phase via radioimmunoassay. We found that the estradiol level was highest in the proestrous and lowest in the diestrous. However, ovariectomy or treatment with the aromatase inhibitor letrozole significantly decreased estradiol levels compared to that of rats in diestrous. Western blotting showed that ovariectomy or letrozole treatment significantly decreased ERα and Bcl-2 protein expression and dramatically increased Bax protein expression compared with the rats in diestrous or proestrous. Rats also underwent 2h of ischaemia via middle cerebral artery occlusion followed by a 24-h reperfusion. Ovariectomy or letrozole treatment significantly decreased the neurological scores and the number of intact neurons detected via Nissl staining and dramatically increased the infarct volume detected via TTC staining and the extent of apoptosis detected via TUNEL staining and Western blotting for cleaved-caspase 3 protein expression. These results demonstrate that endogenous estrogen alleviates ischaemia-reperfusion injury by maintaining Bcl-2 expression via ERα signalling pathway and highlight the neuroprotective effects of endogenous estrogen during different stages of the estrous cycle, providing preliminary information on the underlying mechanism of this process. Copyright © 2017 Elsevier B.V. All rights reserved.

Does the method of expression of venous blood affect ischaemia/reperfusion damage in tourniquet use? An experimental study on rabbits.

PubMed

Iltar, Serkan; Kılınç, Cem Yalın; Alemdaroğlu, Kadir Bahadır; Ozcan, Selahattin; Aydoğan, Nevres Hürriyet; Sürer, Hatice; Kılınç, Aytün Şadan

2013-11-01

The aim of this study was to compare the ischaemia and reperfusion phases of two tourniquet application models (Group 1: expressing the blood by a sterile rubber bandage and Group 2: elevation of the limb for several minutes) using an analysis of ischaemia/reperfusion parameters and blood pH. Sixteen New Zealand rabbits were used. Muscle samples were extracted from the triceps surae; at phase A (baseline: just before tourniquet application), phase B (ischaemia: 3h after tourniquet inflation) and phase C (2h after tourniquet deflation). Nitrite, nitrate, reduced glutathione, myeloperoxidase, malondyaldehyde were measured in the samples. Blood pH was also measured at each phase. Group 2 had significantly decreased nitrite (p=0.007) and nitrate (p=0.01) levels compared to Group 1 while passing from phase A to phase B. The pH decrease through the phases was significant within Group 1 (p=0.006) and was not significant within Group 2 (p=0.052). Lower levels of NO metabolites nitrate and nitrite, result from tourniquet use with incomplete venous blood expression by elevation. Also, with this technique severe acidosis is less likely to occur than when a tourniquet is used with expression of the venous blood by rubber bandage. These findings may help in the decision of which tourniquet technique is to be used for potentially long operations which may exceed 2h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

PubMed

Ghoshal, Uday C; Gwee, Kok-Ann

2017-07-01

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

PubMed

Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

2016-07-01

We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

Endocrine disruptive effects of polychlorinated aromatic hydrocarbons on intestinal cholecystokinin in rats.

PubMed

Lee, H M; He, Q; Englander, E W; Greeley, G H

2000-08-01

The ubiquitous and persistent nature of polychlorinated aromatic hydrocarbons (PCAHs) in our environment and the risk of exposure to PCAHs have provoked concern over their potential toxicity. In humans, exposure to PCAHs is aimed chiefly at epithelial cells residing in the intestinal mucosa, because oral intake of contaminated food is a major source of PCAHs. The purpose of this study, therefore, was to examine the effects of chronic exposure to various PCAHs [i.e. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and 2,2'4,4'5,5'-hexachlorobiphenyl (PCB-153)], given alone or as mixtures, on intestinal cholecystokinin (CCK) peptide and messenger RNA levels. We show that chronic PCAH treatment significantly lowers intestinal levels of stored CCK peptide. Intestinal CCK messenger RNA levels are not affected. In addition, 3,3',4,4',5-pentachlorobiphenyl treatment increased intestinal insulin-like growth factor-binding protein-3 levels in a dose-related manner. Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment of intestinal CCK cells lowered levels of CCK-processing enzymes (i.e. prohormone convertase-1 and -2). Together, these data indicate that PCAHs may decrease intestinal levels of stored CCK peptide by affecting the intestinal insulin-like growth factor system and CCK processing.

Effect of acute feeding of diets of varying fatty acid composition on intestinal apolipoprotein expression in the newborn swine.

PubMed

Wang, H; Zhan, R; Hunter, F; Du, J; Black, D

1996-06-01

The purpose of this study was to determine the effects of dietary fatty acids of varying chain lengths and degrees of saturation on intestinal apolipoprotein (apo) B and A-I expression in the newborn piglet. Two-day-old female piglets received one of three isocaloric formulas containing 48% of total calories (120 kcal/kg/24 h) as medium-chain triglycerides (MCT) from MCT oil, intermediate-chain saturated triglycerides (ICST) from coconut oil, or long-chain polyunsaturated triglycerides (LCPUT) from safflower oil by continuous duodenal infusion for 24 h. After in situ radiolabeling, jejunal and ileal mucosal apo B-48 and A-I were immunoprecipitated, and synthesis was expressed as percentage of total protein synthesis. Mucosal apo B and A-I mass was measured by ELISA as nanograms of apoprotein/microgram of total protein. Fifty percent less apo B jejunal synthesis was present in the ICST group versus the MCT and LCPUT groups (0.67 +/- 0.07, 1.19 +/- 0.20, and 1.25 +/- 0.15, respectively, mean +/- SEM, p < 0.05). Jejunal apo B mass was lower in the MCT group versus the ICST and LCPUT groups (0.10 +/- 0.02, 0.21 +/- 0.03, and 0.16 +/- 0.03, respectively, p < 0.05). Ileal apo B synthesis was lowest in the ICST group. No differences were found in ileal apo B mass. Two-fold higher jejunal apo A-I synthesis was found in the LCPUT group versus the MCT and ICST groups (14.18 +/- 1.69, 7.56 +/- 2.63, and 6.36 +/- 0.58, respectively, p < 0.01). No differences were found for jejunal apo A-I mass. In the ileum, the only difference was a higher apo A-I mass in the LCPUT group (p < 0.05). We conclude that in the newborn piglet intestinal apo B and A-I expression is acutely and differentially regulated by dietary lipid varying in fatty acid chain length and saturation. The patterns of regulation are complex and vary among specific apolipoproteins and regions of the small intestine and include co- and posttranslational mechanisms.

Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2.

PubMed

Cario, E

2005-08-01

Toll-like receptors (TLR) and NOD2 are emerging as key mediators of innate host defence in the intestinal mucosa, crucially involved in maintaining mucosal as well as commensal homeostasis. Recent observations suggest new (patho-) physiological mechanisms of how functional versus dysfunctional TLRx/NOD2 pathways may oppose or favour inflammatory bowel disease (IBD). In health, TLRx signalling protects the intestinal epithelial barrier and confers commensal tolerance whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. In disease, aberrant TLRx and/or NOD2 signalling may stimulate diverse inflammatory responses leading to acute and chronic intestinal inflammation with many different clinical phenotypes.

Bidirectional interactions between indomethacin and the murine intestinal microbiota

PubMed Central

Liang, Xue; Bittinger, Kyle; Li, Xuanwen; Abernethy, Darrell R; Bushman, Frederic D; FitzGerald, Garret A

2015-01-01

The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial β-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin — thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses. DOI: http://dx.doi.org/10.7554/eLife.08973.001 PMID:26701907

[EFFICIENCY OF SEROTONIN ADIPINATE IN INTESTINAL DYSFUNCTION IN PATIENTS AFTER COLORECTAL OPERATIONS].

PubMed

Stakanov, A V; Musaeva, T S

2015-01-01

We performed a retrospective analysis of case histories of acute colonic obstruction due to colon cancer A total of 291 patients were divided on two groups: 1--a control group (patients presenting risk of developing intestinal dysfunction with 'basic' therapy, n = 123); 2--the comparison group (n = 57) represented patients who were taken to optimize the post-operative period with the inclusion in the scheme of the basic treatment of serotonin adipinate. The use of serotonin adipinatein treatment of intestinal dysfunction allows fully restore bowel motility to 3rd day.

Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep.

PubMed

Yamaguchi, Kyohei; Lear, Christopher A; Beacom, Michael J; Ikeda, Tomoaki; Gunn, Alistair J; Bennet, Laura

2018-01-08

Fetal heart rate variability is a critical index of fetal wellbeing. Suppression of heart rate variability may provide prognostic information on the risk of hypoxic-ischaemic brain injury after birth. In the present study, we report the evolution of fetal heart rate variability after both mild and severe hypoxia-ischaemia. Both mild and severe hypoxia-ischaemia were associated with an initial, brief suppression of multiple measures of heart rate variability. This was followed by normal or increased levels of heart rate variability during the latent phase of injury. Severe hypoxia-ischaemia was subsequently associated with the prolonged suppression of measures of heart rate variability during the secondary phase of injury, which is the period of time when brain injury is no longer treatable. These findings suggest that a biphasic pattern of heart rate variability may be an early marker of brain injury when treatment or intervention is probably most effective. Hypoxia-ischaemia (HI) is a major contributor to preterm brain injury, although there are currently no reliable biomarkers for identifying infants who are at risk. We tested the hypothesis that fetal heart rate (FHR) and FHR variability (FHRV) would identify evolving brain injury after HI. Fetal sheep at 0.7 of gestation were subjected to either 15 (n = 10) or 25 min (n = 17) of complete umbilical cord occlusion or sham occlusion (n = 12). FHR and four measures of FHRV [short-term variation, long-term variation, standard deviation of normal to normal R-R intervals (SDNN), root mean square of successive differences) were assessed until 72 h after HI. All measures of FHRV were suppressed for the first 3-4 h in the 15 min group and 1-2 h in the 25 min group. Measures of FHRV recovered to control levels by 4 h in the 15 min group, whereas the 25 min group showed tachycardia and an increase in short-term variation and SDNN from 4 to 6 h after occlusion. The measures of FHRV then progressively

Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels. Acute intestinal inflammation facilitates infection of the vertebrate host

Transmural Intestinal Wall Permeability in Severe Ischemia after Enteral Protease Inhibition

PubMed Central

Altshuler, Angelina E.; Lamadrid, Itze; Li, Diana; Ma, Stephanie R.; Kurre, Leena; Schmid-Schönbein, Geert W.; Penn, Alexander H.

2014-01-01

In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases) and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein) in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP) inhibitors (doxycycline, GM 6001), and serine protease inhibitor (tranexamic acid) in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation) for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid) did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen across the wall

Daily Changes in Composition and Diversity of the Intestinal Microbiota in Patients with Anorexia Nervosa: A Series of Three Cases.

PubMed

Kleiman, Susan C; Glenny, Elaine M; Bulik-Sullivan, Emily C; Huh, Eun Young; Tsilimigras, Matthew C B; Fodor, Anthony A; Bulik, Cynthia M; Carroll, Ian M

2017-09-01

Anorexia nervosa, a severe psychiatric illness, is associated with an intestinal microbial dysbiosis. Individual microbial signatures dominate in healthy samples, even over time and under controlled conditions, but whether microbial markers of the disorder overcome inter-individual variation during the acute stage of illness or renourishment is unknown. We characterized daily changes in the intestinal microbiota in three acutely ill patients with anorexia nervosa over the entire course of hospital-based renourishment and found significant, patient-specific changes in microbial composition and diversity. This preliminary case series suggests that even in a state of pathology, individual microbial signatures persist in accounting for the majority of intestinal microbial variation. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

PubMed Central

Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

2001-01-01

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

The expression of REG 1A and REG 1B is increased during acute amebic colitis.

PubMed

Peterson, Kristine M; Guo, Xiaoti; Elkahloun, Abdel G; Mondal, Dinesh; Bardhan, Pradip K; Sugawara, Akira; Duggal, Priya; Haque, Rashidul; Petri, William A

2011-09-01

Entamoeba histolytica, a protozoan parasite, is an important cause of diarrhea and colitis in the developing world. Amebic colitis is characterized by ulceration of the intestinal mucosa. We performed microarray analysis of intestinal biopsies during acute and convalescent amebiasis in order to identify genes potentially involved in tissue injury or repair. Colonic biopsy samples were obtained from 8 patients during acute E. histolytica colitis and again 60 days after recovery. Gene expression in the biopsies was evaluated using microarray, and confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). REG 1A and REG 1B were the most up-regulated of all genes in the human intestine in acute versus convalescent E. histolytica disease: as determined by microarray, the levels of induction were 7.4-fold and 10.7 fold for REG 1A and B; p=0.003 and p=0.006 respectively. Increased expression of REG 1A and REG 1B protein in the colonic crypt epithelial cells during acute amebiasis was similarly observed by immunohistochemistry. Because REG 1 protein is anti-apoptotic and pro-proliferative, and since E. histolytica induces apoptosis of the intestinal epithelium as part of its disease process, we next tested if REG 1 might be protective during amebiasis by preventing parasite-induced apoptosis. Intestinal epithelial cells from REG 1-/- mice were found to be more susceptible to spontaneous, and parasite-induced, apoptosis in vitro (p=0.03). We concluded that REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis. Published by Elsevier Ireland Ltd.

Nonstrangulating intestinal infarction associated with Strongylus vulgaris in referred Danish equine cases.

PubMed

Nielsen, M K; Jacobsen, S; Olsen, S N; Bousquet, E; Pihl, T

2016-05-01

Strongylus vulgaris is a pathogenic helminth parasite infecting horses and was once considered to be the primary cause of colic. Migrating larvae cause ischaemia and infarction of intestinal segments. This knowledge is derived from case reports and experimental inoculations of parasite-naïve foals, and it remains unknown to what extent the parasite is associated with different types of colic. To evaluate the role of S. vulgaris as a risk factor for different types of colic in horses. A retrospective case-control study among horses referred with abdominal pain to the University of Copenhagen Large Animal Teaching Hospital during 2009-2011. Each colic case was matched with an equid of the same type (pony, Warmblooded or Coldblooded), age, sex and admitted in the same month and year but for problems unrelated to the gastrointestinal tract. Serum samples were analysed for antibodies to migrating S. vulgaris larvae using a recently developed enzyme-linked immunosorbent assay (ELISA). The following 4 case definitions were used: colic sensu lato, i.e. all horses presenting with colic (n = 274), with further subgroups, i.e. undiagnosed colics (n = 48), strangulating obstructions (n = 76) and nonstrangulating infarctions (n = 20). Strongylus vulgaris antibody levels were similar to control values in colics sensu lato and horses with undiagnosed colic. In contrast, nonstrangulating intestinal infarctions were significantly associated with positive S. vulgaris ELISAs (odds ratio 5.33, 95% confidence interval 1.03-27.76, P = 0.05). Also, horses with nonstrangulating infarctions had a significantly higher occurrence of positive ELISAs than horses with strangulating obstructions (odds ratio 3.79, 95% confidence interval 1.34-10.68, P = 0.01) and the colic sensu lato group (odds ratio 3.09, 95% confidence interval 1.20-8.01, P = 0.02). Nonstrangulating intestinal infarction was strongly associated with S. vulgaris-specific antibodies, whereas the more broadly defined

Unusual case of acute appendicitis with left upper quadrant abdominal pain.

PubMed

Tawk, Charbel M; Zgheib, Rana R; Mehanna, Seba

2012-01-01

Acute appendicitis is one of the most frequent causes of surgical abdominal pain presenting to the Emergency Department. The diagnosis is confirmed by a set of clinical signs, blood tests and imaging. The typical presentation consists of periumbilical pain radiating to the right lower quadrant with peritoneal reaction on palpation (Mac Burney). In this article, we report a case of acute appendicitis presenting with a left upper quadrant pain due to intestinal malrotation and we describe the radiologic findings on computed tomography. With an Alvarado score of 4 and a nonconclusive abdominal U/S, the diagnosis of acute appendicitis was a long shot. Persistence of pain and increasing inflammatory parameters in her blood exams pushed the medical team to further investigate and a CT scan revealed intestinal malrotation with acute appendicitis. An examining physician should not be mislead by the atypical presentation of acute appendicitis and should bear in mind the diagnosis to avoid serious complications. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

PubMed Central

Gottwald, E; Gottwald, M; Dhein, S

1998-01-01

Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. 

 Keywords: dispersion;  epicardial activation-recovery interval;  ischaemia PMID

Catecholamine-mediated arrhythmias in acute myocardial infarction. Experimental evidence and role of beta-adrenoceptor blockade.

PubMed

Opie, L H; Lubbe, W F

1979-11-24

Ventricular fibrillation is a major mechanism of sudden death. The cellular link between catecholamine activity and the development of serious ventricular arrhythmias may be in the formation of cyclic adenosine monophosphate (cAMP). Cyclic AMP and agents promoting cAMP accumulation allow development of slow responses which, especially in the presence of regional ischaemia, could develop into ventricular fibrillation. The role of beta-antagonist agents in the therapy of acute myocardial infarction is analysed in relation to the hypothesis linking cAMP and ventricular fibrillation. Reasons for the limited effectiveness of anti-arrhythmic therapy with beta-antagonist agents are given.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

PubMed

Kupčinskas, Juozas; Gedgaudas, Rolandas; Hartman, Hannes; Sippola, Tomi; Lindström, Outi; Johnson, Colin D; Regnér, Sara

2018-07-01

The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti

Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice

PubMed Central

Westbrook, Aya M.; Wei, Bo; Braun, Jonathan; Schiestl, Robert H.

2011-01-01

Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4+ and CD8+ T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer. PMID:21520038

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective tissue disorders.

PubMed

Shammas, R L; Hwang, B H; Levin, L S; Richard, M J; Ruch, D S; Mithani, S K

2017-10-01

All patients (36 hands) with connective tissue disorders who underwent periarterial sympathectomy of the hand alone or in conjunction with vascular bypass at our institution between 1995-2013 were reviewed. The durable resolution of ulcers was significantly higher in patients treated by periarterial sympathectomy and bypass than in patients treated by periarterial sympathectomy alone. Although there were more digital amputations in patients treated by periarterial sympathectomy alone, the difference was not statistically significant. Vascular bypass in conjunction with sympathectomy may be better than sympathectomy alone in patients with digital ischaemia related to connective tissue disorders. IV.

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity.

PubMed

Estaki, Mehrbod; DeCoffe, Daniella; Gibson, Deanna L

2014-11-14

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion.

PubMed Central

Thiemermann, C.; Thomas, G. R.; Vane, J. R.

1989-01-01

1. Defibrotide, a single-stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2. The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3. Defibrotide (32 mg kg-1 bolus + 32 mg kg-1 h-1, i.v.) either with or without co-administration of indomethacin (5 mg kg-1 x 2, i.v.) was administered 5 min after occlusion of the left anterior-lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4. Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5. Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6. The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed. PMID:2758223

[Use of Gastrografin(®) in the management of adhesion intestinal obstruction].

PubMed

Mora López, Laura; Serra-Aracil, Xavier; Llaquet Bayo, Heura; Navarro Soto, Salvador

2013-01-01

Adhesions are the most important cause of intestinal obstruction. Approximately 25% of surgical admissions for acute abdominal conditions are due to intestinal obstruction. Better diagnostic and treatment methods of intestinal obstruction could potentially reduce mortality rate to 5-10%. Gastrografin(®) could contribute to this achieve this. To present a protocol to treat adhesion intestinal obstruction with Gastrografin(®) that is safe, and allows shorter hospital stays and shorter time between admission and surgery. All patients with adhesion intestinal obstruction without symptoms of strangulation were treated with Gastrografin(®), intravenous fluids and nasogastric tube. Those in whom contrast reach the colon in 8, 12 or 24hours were considered to have partial obstruction, and were fed orally. If Gastrografin(®) failed in the following 24hours, a laparotomy was performed. Out of a total of 211 episodes (164 patients), 170 episodes received contrast and in 142 cases Gastrografin(®) reached the colon (104 episodes at 8h, 11 at 12h, and 27 at 24h). A laparotomy was required in 28 patients because of failed treatment, and in another 5 for other causes. A management protocol for adhesion intestinal obstruction with Gastrografin(®) is safe, reduces morbidity and mortality, and leads to a shorter hospital stay. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

[Volvulus of the cecum: a rare cause of intestinal occlusion: about two cases].

PubMed

Mazine, Khalid; Elbouhaddouti, Hicham; Toughrai, Imane; Mouaqit, Ouadie; Benjelloun, Elbachir; Ousadden, Abdelmalek; Taleb, Khalid Ait

2017-01-01

The cecum is the second part of the colon that is most commonly affected by the volvulus after sigmoid colon and before left corner and the transverse colon. This condition occurs in patients with abnormally mobile cecum. Volvulus is characterized by torsion or tilt. Clinically, it appears as bowel obstruction due to acute strangulation. Abdominal x-ray without treatment and abdominal CT scan are the radiological procedures of choice in the diagnosis of volvulus of the cecum. Treatment is based on emergency surgical excision of the cecum and of the terminal ileum. We report two cases of patients with volvulus of the cecum admitted to the emergency department with acute intestinal obstruction. In both patients, the diagnosis was confirmed by abdomino-pelvic CT scan and the treatment was based on ileocolic resection with immediate restoration of the intestinal continuity. The postoperative course was uneventful.

Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion.

PubMed

Sánchez, Gregorio Martínez; Rodríguez H, María A; Giuliani, Attilia; Núñez Sellés, Alberto J; Rodríguez, Niurka Pons; León Fernández, Olga Sonia; Re, L

2003-03-01

The effect of Mangifera indica L. extract (Vimang) on treatment of injury associated with hepatic ischaemia/reperfusion was tested. Vimang protects from the oxidative damage induced by oxygen-based free radicals as shown in several in vitro test systems conducted. The ability of Vimang to reduce liver damage was investigated in rats undergoing right-lobe blood fl ow occlusion for 45 min followed by 45 min of reperfusion. The ischaemia/reperfusion model leads to an increase of transaminase (ALT and AST), membrane lipid peroxidation, tissue neutrophil in filtration, DNA fragmentation, loss of protein -SH groups, cytosolic Ca2+ overload and a decrease of catalase activity. Oral administration of Vimang (50, 110 and 250 mg/kg, b.w.) 7 days before reperfusion, reduced transaminase levels and DNA fragmentation in a dose dependent manner (p < 0.05). Vimang also restored the cytosolic Ca2+ levels and inhibited polymorphonuclear migration at a dose of 250 mg/kg b.w., improved the oxidation of total and non protein sulfhydryl groups and prevented modification in catalase activity, uric acid and lipid peroxidation markers (p < 0.05). These data suggest that Vimang could be a useful new natural drug for preventing oxidative damage during hepatic injury associated with free radical generation. Copyright 2003 John Wiley & Sons, Ltd.

123I-BMIPP fatty acid analogue imaging is a novel diagnostic and prognostic approach following acute myocardial infarction.

PubMed

Biswas, S K; Sarai, M; Hishida, H; Ozaki, Y

2009-10-01

Fatty acid oxidation is the most efficient mode of myocardial energy production which requires a large amount of oxygen. Thus, alteration of fatty acid oxidation is considered to be a sensitive marker of ischaemia and myocardial damage. (123)I-BMIPP ([123]I-beta-methyl-p-iodophenylpentadecanoic acid) is a newly-investigated single-photon branching free fatty acid radiopharmaceutical with slow metabolism; thus, it is well-suited for single-photon emission computed tomography (SPECT). Assessment of fatty acid metabolism by radionuclide techniques has a potential role for the early detection of myocardial ischaemia and the assessment of the severity of ischaemic heart disease. Although stable patients with a healed myocardial infarction may have a relatively good prognosis, risk stratification in the predischarge period should be valuable for deciding upon appropriate management. In this respect, the presence of discordant BMIPP uptake relative to (201)Tl perfusion appears to be the best predictor of future cardiac events among all other cardiovascular imaging modalities. Since discordant BMIPP uptake correlates well with redistribution on stress (201)Tl imaging and perfusion-metabolism mismatch on positron emission tomography, it is considered that such BMIPP and (201)Tl discordance may identify a high-risk subgroup among patients with acute myocardial infarction. A BMIPP scan may reflect prior severe ischaemia after recovery of perfusion, the so-called "ischaemic memory". Gated BMIPP SPECT has been recently introduced for simultaneous assessment of myocardial metabolism and ventricular function. Such a new technique seems to be valuable for a better understanding of the pathophysiological state of heart failure and cardiomyopathy.

Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS.

PubMed

Lange, Frédéric; Dunne, Luke; Tachtsidis, Ilias

2017-01-01

We demonstrate the ability of a 16-wavelength time domain near-infrared spectroscopy system to monitor changes in oxy- and deoxy haemoglobin ([HbO 2 ] [HHb]) and the oxidation of cytochrome-c-oxidase ([oxCCO]), during forearm ischaemia. We tested two methods to retrieve the concentration changes. The first uses the measured changes in light attenuation and the modified Beer-Lambert law, and the second uses the absorption and scattering estimated by the measured time-point spread function. The system is able to retrieve the concentration changes with both methods, giving similar results. At the end of forearm ischaemia (t = 5 min), we measured an increase in [HHb] of 16.77 ± 2.52 and 16.37 ± 2.33 μMol, and a decrease in [HbO 2 ] of -6.12 ± 1.62 and -5.57 ± 2.02 μMol for method 1 and 2, respectively. At that same time, the changes in [oxCCO] were -0.36 ± 0.33 and -1.40 ± 1.20 μMol, for method 1 and 2, respectively. These small changes in [oxCCO], despite a huge change in haemoglobin, demonstrate the absence of crosstalk and are comparable to previous measurements using broadband NIRS.

A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats

PubMed Central

Takeo, Satoshi; Niimura, Makiko; Miyake-Takagi, Keiko; Nagakura, Akira; Fukatsu, Tomoko; Ando, Tsuyoshi; Takagi, Norio; Tanonaka, Kouichi; Hara, Junko

2003-01-01

Accumulated evidence indicates that the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signal transduction system may be linked to learning and memory function. The effects of nefiracetam, which has been developed as a cognition enhancer, on spatial memory function and the AC/cAMP/PKA/CREB signal transduction system in rats with sustained cerebral ischaemia were examined. Microsphere embolism (ME)-induced sustained cerebral ischaemia was produced by injection of 700 microspheres (48 μm in diameter) into the right hemisphere of rats. Daily oral administration of nefiracetam (10 mg kg−1 day−1) was started from 15 h after the operation. The delayed treatment with nefiracetam attenuated the ME-induced prolongation of the escape latency in the water maze task that was examined on day 7 to 9 after ME, but it did not reduce the infarct size. ME decreased Ca2+/calmodulin (CaM)-stimulated AC (AC-I) activity, cAMP content, cytosolic PKA Cβ level, nuclear PKA Cα and Cβ levels, and reduced the phosphorylation and DNA-binding activity of CREB in the nucleus in the right parietal cortex and hippocampus on day 3 after ME. The ME-induced changes in these variables did not occur by the delayed treatment with nefiracetam. These results suggest that nefiracetam preserved cognitive function, or prevented cognitive dysfunction, after sustained cerebral ischaemia and that the effect is, in part, attributable to the prevention of the ischaemia-induced impairment of the AC/cAMP/PKA/CREB signal transduction pathway. PMID:12598418

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels.

PubMed

Wong, Jonathan; Davis, Philip; Patidar, Ashish; Zhang, Yonglong; Vilar, Enric; Finkelman, Malcolm; Farrington, Ken

2017-01-01

In healthy individuals, an acute inflammatory response occurs after intense exercise due to gut ischaemia and intestinal bacterial endotoxin translocation into the bloodstream. This process maybe exacerbated in patients who exercise during dialysis due to large volume shifts experienced by many during haemodialysis (HD). The acute effect of intra-dialytic exercise on blood endotoxins and inflammation is not known. The effect of intra-dialytic exercise on blood endotoxin and inflammation was investigated in 10 patients and compared with resting haemodialysis. Blood was measured for endotoxin and inflammatory biomarkers before and after dialysis. With the exception of one sample, all samples tested negative for endotoxin. Intra-dialytic exercise attenuated the rise of interleukin-6, tumour necrosis factor-α and high-sensitivity C-reactive protein after the HD procedure. Intra-dialytic exercise was not associated with an observable rise in blood endotoxin, although it may ameliorate the inflammatory effects of the HD procedure. Larger studies are needed to confirm this finding. © 2017 S. Karger AG, Basel.

Intestinal obstruction caused by omphalomesenteric duct remnant: usefulness of laparoscopy.

PubMed

Bueno Lledó, J; Serralta Serra, A; Planeéis Roig, M; Dobón Giménez, F; Ibáñez Palacín, F; Rodero Rodero, R

2003-10-01

The anomalies related to omphalomesenteric duct remnant constitute an uncommon cause of intestinal obstruction, of which Meckel"s diverticulum and its variants represent the most important clinical presentation. In most cases they are asymptomatic and usually affect young patients. When symptomatic, they usually present episodes of gastrointestinal bleeding or acute abdomen syndromes caused by strangulation of intestinal loops as a result of fibrous intraabdominal remnants or inflammation produced by the diverticulum. In most cases, the unexpected presence of these alterations makes intraoperative diagnosis necessary. Treatment is surgical and consists in exeresis of the diverticulum or the fibrous band causing the clinical picture. We report two cases of persistence of the vitelline duct resolved by laparoscopic approach.

Myocardial ischaemia and cardiac pain – a mysterious relationship

PubMed Central

Fisher, Mike

2013-01-01

Pain related to cardiac disease has been recognised for centuries. However, the precise mechanisms of angina pectoris remain bafflingly obscure. Conventional cardiological angina management concentrates on methods to improve oxygen delivery to cardiac myocytes as our understanding of cardiac muscle cells’ response to hypoxia increases. In common with other chronic visceral pain syndromes, little is understood about how pain signals are generated and propagated by visceral nerves. Improved imaging and other physiological assessments have demonstrated important central nervous system (CNS) responses to myocardial ischaemia, including activation of CNS areas known to be ‘key players’ in chronic pain syndromes. Patients with stable angina usually have an excellent prognosis, especially if left ventricular function is preserved. Educating patients about their condition, teaching simple techniques known to help chronic pain patients and introducing targeted pain treatments specific to angina can be extremely helpful adjuncts to conventional cardiological treatments and will often bring about significant improvements in quality of life. PMID:26516494

Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

Cardioprotective effect of hyperthyroidism on the stunned rat heart during ischaemia-reperfusion: energetics and role of mitochondria.

PubMed

Ragone, María Inés; Bonazzola, Patricia; Colareda, Germán A; Consolini, Alicia E

2015-06-01

What is the central question of this study? Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+) handling of the postischaemic stunned heart? What is the main finding and its importance? Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia. Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'-triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c. daily with 20 μg kg(-1) triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by

Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat.

PubMed

Pollack, P F; Adamson, C; Koldovsky, O

1989-04-15

Because of the presence of bombesin-like immunoreactivity in milk, we investigated if enteral administration of bombesin affects the intestinal luminal content of trypsin and protein in 12-14-day-old rats. Bombesin (40 micrograms/kg), given either orogastrically or subcutaneously, produced a significant elevation in the intestinal content of trypsin activity. Thus, enterally-administered bombesin can produce acute biologic effects in suckling rats.

Anti-apoptotic and myocardial protective effects of ethyl pyruvate after regional ischaemia/reperfusion myocardial damage in an in vivo rat model.

PubMed

Shim, Haeng Seon; Lee, Wang Gyu; Kim, Yeon A; Han, Jeong Yeol; Park, Miyeong; Song, Yun Gyu; Kim, Joon Soo; Shin, Il-Woo

2017-09-01

The integration of reactive oxygen species is strongly associated with important pathophysiological mechanisms that mediate myocardial ischaemia/reperfusion (I/R) damage. Pyruvate is an efficacious scavenger of reactive oxygen species and a previous study has shown that ethyl pyruvate (EP) has a myocardial protective effect against regional I/R damage in an in vivo rat model. The purpose of this study was to determine whether the myocardial protective effect of EP is associated with anti-apoptosis. Rats were allocated to receive EP dissolved in lactated Ringer's solution or lactated Ringer's solution alone, via intraperitoneal infusion one hour before ischaemia. They were exposed to 30 minutes of ischaemia followed by reperfusion of the left coronary artery territory over two hours. Anti-apoptotic effects were checked using several biochemical parameters after two hours of reperfusion. Apoptosis was analysed using measured caspase-3 activity, Western blotting of B-cell lymphoma 2 (Bcl-2) family protein cleaved by caspase-3, and assessment of DNA laddering patterns and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining test. In ischaemic myocardium, EP increased Bcl-2 expression, but reduced Bcl-2-associated X protein and cleaved caspase-3 expressions. EP reduced the expression of DNA laddering and the number of myocardial I/R-damaged TUNEL-positive cells. This study demonstrated that EP has an anti-apoptotic effect after regional I/R damage in an in vivo rat heart model. The myocardial protective effect of EP may be related to its anti-apoptotic effect. Copyright: © Singapore Medical Association

Comparing short versus standard-length balloon for intra-aortic counterpulsation: results from a porcine model of myocardial ischaemia-reperfusion.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-05-01

We compare a short and a standard-size balloon with same filling volumes to verify the differences in terms of visceral flow, coronary circulation and haemodynamic performance during aortic counterpulsation in an animal model of myocardial ischaemia-reperfusion injury. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned to have intra-aortic balloon counterpulsation (IABP) with a 40-ml short-balloon (n = 6) or a 40-ml standard-length balloon (n = 6), or to undergo no IABP implantation (controls, n = 6). Haemodynamics and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric flows increased significantly at tR1 only in the short-balloon group (P < 0.001) and it was constantly higher than in the standard-balloon group regardless of mean arterial pressure, systemic vascular resistance and cardiac output (CO; all, P < 0.001). Renal blood flows were significantly increased during IABP treatment with values constantly and significantly higher in short balloons at any following experimental step (all, P < 0.05). IABP improved CO and coronary blood flow, and reduced afterload, myocardial resistances and myocardial oxygen consumption without differences between the short and the standard-length balloon (all, P > 0.05). The short balloon prevents visceral ischaemia and, compared with the standard-size balloon, it does not lose IABP beneficial cardiac and coronary-related effects. Further studies are warranted to confirm our findings. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Houttuynia cordata polysaccharides ameliorate pneumonia severity and intestinal injury in mice with influenza virus infection.

PubMed

Zhu, Haiyan; Lu, Xiaoxiao; Ling, Lijun; Li, Hong; Ou, Yingye; Shi, Xunlong; Lu, Yan; Zhang, Yunyi; Chen, Daofeng

2018-05-23

Hottuynia cordata is an important traditional Chinese medicine for the treatment of respiratory diseases including bacterial and viral infections. Polysaccharides isolated from Houttuynia cordata (HCP), as its main ingredients, have been demonstrated to ameliorate the LPS-induced acute lung injury in mice. The study aimed to determine the protective effects of HCP on multiple organ injury in influenza A virus (IAV) H1N1 infected mice and its primary mechanisms in anti-inflammation and immune regulation. Mice were inoculated with IAV H1N1 and then treated with 20 or 40 mg/kg/d of HCP for survival test and acute lung-gut injury test. The treatment with HCP resulted in an increase in the survival rate of H1N1 infected mice and the protection from lung and intestine injury, accompanied with the reduced virus replication. HCP markedly decreased the concentration of pulmonary proinflammatory cytokines/chemokines and the number of intestinal goblet cells, and strengthened the intestinal physical and immune barrier, according to the increase of sIgA and tight junction protein (ZO-1) in intestine. At the same time, the inhibition of inflammation in lung and gut was related to the suppressing of the expression of TLR4 and p-NFκB p65 in lung. These results indicated that HCP ameliorated lung and intestine injury induced by IAV attack. The mechanisms were associated with inhibition of inflammation, protection of intestinal barrier and regulation of mucosal immunity, which may be related to the regulation of gut-lung axis. As an alternative medicine, HCP may have clinical potential to treat IAV infection in human beings. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute surgical abdomen due to phytobezoar-induced ileal obstruction.

PubMed

Salemis, Nikolaos S; Panagiotopoulos, Nikolaos; Sdoukos, Nikolaos; Niakas, Evangelos

2013-01-01

Phytobezoar-induced small bowel obstruction is an uncommon clinical entity accounting for 2-4.8% of all mechanical intestinal obstructions. In addition, presentation with features of acute surgical abdomen is extremely rare, accounting for only 1% of the patients. The aim of this report is to present a very rare case of a phytobezoar-induced small bowel obstruction in a male patient who presented with acute surgical abdomen. A correct preoperative diagnosis was made based on the patient's history and characteristic imaging features on the emergency computed tomography (CT) scan. A 55-year-old man with previous gastrectomy presented with typical manifestations of acute abdomen. CT scan demonstrated dilatated small bowel loops and an intraluminal ileal mass with a mottled appearance. At exploratory laparotomy, a phytobezoar was found impacted in the terminal ileum and was removed through an enterotomy. Phytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen. The presence of a well-defined intraluminal mass with a mottled gas pattern on emergency CT scan is suggestive of an intestinal phytobezoar. Copyright © 2013 Elsevier Inc. All rights reserved.

Cholesterol auxotrophy and intolerance to ezetimibe in mice with SREBP-2 deficiency in the intestine.

PubMed

Rong, Shunxing; McDonald, Jeffrey G; Engelking, Luke J

2017-10-01

SREBP-2 activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in the intestine, we generated a mouse model ( Vil-BP2 -/- ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2 -/- mice had reduced expression of genes required for sterol synthesis, in vivo sterol synthesis rates, and epithelial cholesterol contents. On a cholesterol-free diet, the mice displayed chronic enteropathy with histological abnormalities of both villi and crypts, growth restriction, and reduced survival that was prevented by supplementation of cholesterol in the diet. Likewise, SREBP-2-deficient enteroids required exogenous cholesterol for growth. Blockade of luminal cholesterol uptake into enterocytes with ezetimibe precipitated acutely lethal intestinal damage in Vil-BP2 -/- mice, highlighting the critical interplay in the small intestine of sterol absorption via NPC1L1 and sterol synthesis via SREBP-2 in sustaining the intestinal mucosa. These data show that the small intestine requires SREBP-2 to drive cholesterol synthesis that sustains the intestinal epithelia when uptake of cholesterol from the gut lumen is not available, and provide a unique example of cholesterol auxotrophy expressed in an intact, adult mammal. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis

PubMed Central

Zhang, Chen-Long; Lin, Zi-Qi; Zhang, Xiao-Xin; Guo, Jia; Wu, Wei; Shi, Na; Deng, Li-Hui; Chen, Wei-Wei; Zhang, Xiao-Ying; Bharucha, Shameena; Huang, Wei; Sutton, Robert; Windsor, John A.

2017-01-01

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC. PMID:28529530

Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia.

PubMed

He, Yan; Yuan, Xiaoming; Zhou, Guangrong; Feng, Aiwen

2018-01-01

Insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) play a role in the maintenance of gut mucosal barrier function. Nevertheless, IGF-I/IGFBP-3 and tight junction protein (TJP) expression in small intestinal mucosa are often impaired during endotoxemia. In this model of acute endotoxemia, the regulatory effect of berberine on IGF-I/IGFBP-3 and TJP expression in ileal mucosa was evaluated. The findings revealed systemic injection of lipopolysaccharide (LPS) suppressed mRNA and protein expression of IGF-I and IGFBP-3, but berberine ameliorated their production. LPS injection inhibited occludin and claudin-1 protein generation, and this inhibitory effect of LPS was abolished by berberine. Inhibition of IGF-I/IGFBP-3 signaling by AG1024 or siRNAs reduced berberine-induced occludin and claudin-1 production. Additionally, GW9662 was found to repress berberine-induced IGF-I/IGFBP-3 expression, indicating of a cross-link between PPARγ and IGF-I/IGFBP-3 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study.

PubMed

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-02-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin-eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion.

PubMed Central

Masini, E.; Lupini, M.; Mugnai, L.; Raspanti, S.; Mannaioni, P. F.

1995-01-01

1. Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2. In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration-dependent fashion. At the highest concentration studied (10(-6) M), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3. The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NG-monomethyl-L-arginine (L-NMMA, 10(-4) M), an inhibitor of nitric oxide synthase (NOS). 4. The endothelium-dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10(-4) M). 5. In guinea-pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6. Reperfusion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7. The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed. PMID:7582482

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate.

PubMed

Poon, Selina; Lu, Xiaohua; Smith, Raymond A A; Ho, Pei; Bhakoo, Kishore; Nurcombe, Victor; Cool, Simon M

2018-05-18

Peripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF 165 ) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF 165 . Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF 165 against thermal and enzyme degradation in vitro, and isolated VEGF 165 from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites.

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

PubMed

Lin, Yu-Hui; Liang, Hai-Ying; Xu, Ke; Ni, Huan-Yu; Dong, Jian; Xiao, Hui; Chang, Lei; Wu, Hai-Yin; Li, Fei; Zhu, Dong-Ya; Luo, Chun-Xia

2018-02-01

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N 1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N 1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017

Acute GI obstruction.

PubMed

Hucl, Tomas

2013-10-01

Acute gastrointestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The blockage can occur at any level throughout the gastrointestinal tract. The clinical symptoms depend on the level and extent of obstruction. Various benign and malignant processes can produce acute gastrointestinal obstruction, which often represents a medical emergency because of the potential for bowel ischemia leading to perforation and peritonitis. Early recognition and appropriate treatment are thus essential. The typical clinical symptoms associated with obstruction include nausea, vomiting, dysphagia, abdominal pain and failure to pass bowel movements. Abdominal distention, tympany due to an air-filled stomach and high-pitched bowel sounds suggest the diagnosis. The diagnostic process involves imaging including radiography, ultrasonography, contrast fluoroscopy and computer tomography in less certain cases. In patients with uncomplicated obstruction, management is conservative, including fluid resuscitation, electrolyte replacement, intestinal decompression and bowel rest. In many cases, endoscopy may aid in both the diagnostic process and in therapy. Endoscopy can be used for bowel decompression, dilation of strictures or placement of self-expandable metal stents to restore the luminal flow either as a final treatment or to allow for a delay until elective surgical therapy. When gastrointestinal obstruction results in ischemia, perforation or peritonitis, emergency surgery is required. Copyright © 2013. Published by Elsevier Ltd.

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity

PubMed Central

Estaki, Mehrbod; DeCoffe, Daniella; Gibson, Deanna L

2014-01-01

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium. PMID:25400448

[Acute hepatic vascular complications].

PubMed

Ochs, A

2011-07-01

Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach.

Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats.

PubMed

Gan, Xiaoliang; Liu, Dezhao; Huang, Pinjie; Gao, Wanling; Chen, Xinzhi; Hei, Ziqing

2012-06-01

Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.

Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelenak, Kamil, E-mail: zelenak@unm.sk; Sinak, Igor; Janik, Jan

2013-06-15

Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

ERIC Educational Resources Information Center

Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

2008-01-01

Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

Ischaemia-reperfusion injury in orthotopic mouse lung transplants – a scanning electron microscopy study

PubMed Central

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-01-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin–eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. PMID:21272104

In vivo imaging of induction of heat-shock protein-70 gene expression with fluorescence reflectance imaging and intravital confocal microscopy following brain ischaemia in reporter mice.

PubMed

de la Rosa, Xavier; Santalucía, Tomàs; Fortin, Pierre-Yves; Purroy, Jesús; Calvo, Maria; Salas-Perdomo, Angélica; Justicia, Carles; Couillaud, Franck; Planas, Anna M

2013-02-01

Stroke induces strong expression of the 72-kDa heat-shock protein (HSP-70) in the ischaemic brain, and neuronal expression of HSP-70 is associated with the ischaemic penumbra. The aim of this study was to image induction of Hsp-70 gene expression in vivo after brain ischaemia using reporter mice. A genomic DNA sequence of the Hspa1b promoter was used to generate an Hsp70-mPlum far-red fluorescence reporter vector. The construct was tested in cellular systems (NIH3T3 mouse fibroblast cell line) by transient transfection and examining mPlum and Hsp-70 induction under a challenge. After construct validation, mPlum transgenic mice were generated. Focal brain ischaemia was induced by transient intraluminal occlusion of the middle cerebral artery and the mice were imaged in vivo with fluorescence reflectance imaging (FRI) with an intact skull, and with confocal microscopy after opening a cranial window. Cells transfected with the Hsp70-mPlum construct showed mPlum fluorescence after stimulation. One day after induction of ischaemia, reporter mice showed a FRI signal located in the HSP-70-positive zone within the ipsilateral hemisphere, as validated by immunohistochemistry. Live confocal microscopy allowed brain tissue to be visualized at the cellular level. mPlum fluorescence was observed in vivo in the ipsilateral cortex 1 day after induction of ischaemia in neurons, where it is compatible with penumbra and neuronal viability, and in blood vessels in the core of the infarction. This study showed in vivo induction of Hsp-70 gene expression in ischaemic brain using reporter mice. The fluorescence signal showed in vivo the induction of Hsp-70 in penumbra neurons and in the vasculature within the ischaemic core.

Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

PubMed

Shi, Guang-Xia; Wang, Xue-Rui; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Zeng, Xiang-Hong; Xu, Qian; Zhu, Wen; Du, Si-Qi; Liu, Cun-Zhi

2015-12-10

In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

Delayed post-ischaemic administration of xenon reduces brain damage in a rat model of global ischaemia.

PubMed

Metaxa, V; Lagoudaki, R; Meditskou, S; Thomareis, O; Oikonomou, L; Sakadamis, A

2014-01-01

Xenon and nitrous oxide have been shown to be neuroprotective in vivo and in vitro, but mainly in models of focal cerebral ischaemia. This study aimed to investigate whether the two gases are able to attenuate cerebral injury after global cerebral ischaemia. Adult male Wistar rats underwent bilateral common carotid artery occlusion and were ventilated for 1 hour with 21% O₂/78% N₂. They were then randomized to three groups which continued to receive atmospheric air, 50% N2O/50% O₂ and 50% Xe/50% O₂ for an additional period of 45 minutes. The number of ischaemic neurons, the cortical volume loss and the immunochemical and molecular expression of c-fos and MMP-9 were evaluated. Xenon reduced the number of ischaemic neurons in the cortex and CA1 hippocampal region (p < 0.001) and decreased the cortical volume loss (p < 0.01). Immunochemical induction of c-fos in the cortex was significantly suppressed (p < 0.01) after administration of xenon. The molecular analysis revealed significant effects of N2O and xenon administration on c-fos and MMP-9 expression. The data indicate that N2O and xenon administration is neuroprotective 1 hour after bilateral common carotid artery occlusion. These findings provide valuable evidence on the beneficial role of N2O and xenon in global cerebral injury.

Intestinal Cancer

MedlinePlus

... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

Prevalence, causes and management outcome of intestinal obstruction in Adama Hospital, Ethiopia.

PubMed

Soressa, Urgessa; Mamo, Abebe; Hiko, Desta; Fentahun, Netsanet

2016-06-04

In Africa, acute intestinal obstruction accounts for a great proportion of morbidity and mortality. Ethiopia is one of the countries where intestinal obstruction is a major cause of morbidity and mortality. This study aims to determine prevalence, causes and management outcome of intestinal obstruction in Adama Hospital in Oromia region, Ethiopia. A hospital based cross-sectional study design was used. Data covering the past three years were collected from hospital medical records of sampled patients. The collected data were checked for any inconsistency, coded and entered into SPSS version 16.0 for data processing and analysis. Descriptive and logistic regression analyses were used. Statistical significance was based on confidence interval (CI) of 95 % at a p-value of < 0.05. 262 patients were admitted with intestinal obstruction. The prevalence of intestinal obstruction was 21.8 % and 4.8 % among patients admitted for acute abdomen surgery and total surgical admissions, respectively. The mortality rate was 2.5 % (6 of 262). The most common cause of small bowel obstruction was intussusceptions in 48 patients (30.9 %), followed by small bowel volvulus in 47 patients (30.3 %). Large bowel obstruction was caused by sigmoid volvulus in 60 patients (69.0 %) followed by colonic tumor in 12 patients (13.8 %). After controlling for possible confounding factors, the major predictors of management outcome of intestinal obstruction were: duration of illness before surgical intervention (adjusted odds ratio (AOR) = 0.49, 95 % CI: 0.25-0.97); intra-operative findings [Viable small bowel volvulus (SBV) (AOR = 0.08, 95 % CI: 0.01-0.95) and viable (AOR = 0.17, 95 % CI: 0.03-0.88)]; completion of intra-operative procedures (bowel resection & anastomosis (AOR = 3.05, 95 % CI: 1.04-8.94); and length of hospital stay (AOR = 0.05, 95 % CI: 0.01-0.16). Small bowel obstruction was more prevalent than large bowel obstruction. Intussusceptions and

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

PubMed

Tan, Xiao-Hua; Zheng, Xiao-Meng; Yu, Li-Xia; He, Jian; Zhu, Hong-Mei; Ge, Xiu-Ping; Ren, Xiao-Li; Ye, Fa-Qing; Bellusci, Saverio; Xiao, Jian; Li, Xiao-Kun; Zhang, Jin-San

2017-11-01

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and K ATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K ATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6

PubMed Central

Wang, Xiaohui; Ha, Tuanzhu; Zou, Jianghuan; Ren, Danyang; Liu, Li; Zhang, Xia; Kalbfleisch, John; Gao, Xiang; Williams, David; Li, Chuanfu

2014-01-01

Aims The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. Methods and results LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. Conclusion miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation. PMID:24576954

Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.

PubMed

Whittington, Hannah J; Ostrowski, Philip J; McAndrew, Debra J; Cao, Fang; Shaw, Andrew; Eykyn, Thomas R; Lake, Hannah; Tyler, Jack; Schneider, Jurgen E; Neubauer, Stefan; Zervou, Sevasti; Lygate, Craig A

2018-03-02

Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localisation of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55±4% in WT vs 29±4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia.

Losartan protects liver against ischaemia/reperfusion injury through PPAR-γ activation and receptor for advanced glycation end-products down-regulation

PubMed Central

Koh, Eun-Ji; Yoon, Seong-Jin; Lee, Sun-Mee

2013-01-01

Background and Purpose PPAR-γ has been reported to be a protective regulator in ischaemia/reperfusion (I/R) injury. The receptor for advanced glycation end-products (RAGE) plays a major role in the innate immune response, and its expression is associated with PPAR-γ activation. Several angiotensin receptor blockers possess partial agonist activities towards PPAR-γ. Therefore, this study investigated the action of losartan, particularly with regard to PPAR-γ activation and RAGE signalling pathways during hepatic I/R. Experimental Approach Mice were subjected to 60 min of ischaemia followed by 6 h of reperfusion. Losartan (0.1, 1, 3 and 10 mg·kg−1) was administered 1 h prior to ischaemia and immediately before reperfusion. GW9662, a PPAR-γ antagonist, was administered 30 min prior to first pretreatment with losartan. Key Results Losartan enhanced the DNA-binding activity of PPAR-γ in I/R. Losartan attenuated the increased serum alanine aminotransferase activity, TNF-α and IL-6 levels, and nuclear concentrations of NF-κB in I/R. GW9662 reversed these beneficial effects. Losartan caused a decrease in apoptosis as assessed by TUNEL assay, in release of cytochrome c and in cleavage of caspase-3, and these effects were abolished by GW9662 administration. Losartan attenuated not only I/R-induced RAGE overexpression, but also its downstream early growth response protein-1-dependent macrophage inflammatory protein 2 level; phosphorylation of p38, ERK and JNK; and subsequent c-Jun phosphorylation. GW9662 reversed these effects of losartan administration. Conclusions and Implications Our findings suggest that losartan ameliorates I/R-induced liver damage through PPAR-γ activation and down-regulation of the RAGE signalling pathway. PMID:23647130

Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

PubMed

Iacovides, S; Avidon, I; Baker, F C

2015-07-01

Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p < 0.01] and follicular [dysmenorrhoeics vs. controls mean (SD): 60 (18) mm vs. 40 (14) mm, p < 0.01] phases of the menstrual cycle. These data show that compared with controls, women who experience severe recurrent dysmenorrhoea have deep-tissue hyperalgesia to ischaemic pain in muscles outside of the referred area of menstrual pain both during the painful menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases.

PubMed

Karrasch, T; Obermeier, F; Straub, R H

2014-06-01

Acute and chronic intestinal inflammation stimulates innate and adaptive immune systems, thereby increasing energy demand of activated immune cells. Energy regulation by systemically released mediators is of critical importance for homeostasis. We wanted to find out how systemic metabolic mediators are affected during intestinal inflammation. A total of 123 patients suffering from Crohn's disease (CD), 76 patients with ulcerative colitis (UC), and 21 healthy controls were recruited. Patients receiving systemic steroids or therapy regimens including biologicals (anti-TNF) were excluded from the study. Serum levels of IL-6, CRP, insulin, glucose, free fatty acid, and RBP-4 were measured by ELISA and RIA. Intestinal inflammation was accompanied by elevated systemic inflammatory para-meters such as IL-6 and CRP in UC and CD and, concomitantly, with elevated insulin levels and increased insulin/glucose ratio in patients with UC. This indicates insulin resistance in liver, muscle, and fat. In addition, intestinal inflammation was associated with elevated levels of circulating free fatty acids in UC and CD, indicating an activation of the organism's appeal for energy-rich substrates (energy appeal reaction). RBP-4 serum levels were also high in acute and chronic intestinal inflammation in UC and CD, which can support insulin resistance. The organism's "energy appeal reaction" in response to acute and chronic inflammation provides free energy in the circulation, which is needed by inflammatory cells. A major mechanism of the redirection program is insulin resistance. New therapeutic strategies might be developed in the future, directly impacting on the storage and utilization of energy-rich fuels. © Georg Thieme Verlag KG Stuttgart · New York.

Registry on acute cardiovascular events during endurance running races: the prospective RACE Paris registry.

PubMed

Gerardin, Benoît; Collet, Jean-Philippe; Mustafic, Hazrije; Bellemain-Appaix, Anne; Benamer, Hakim; Monsegu, Jacques; Teiger, Emmanuel; Livarek, Bernard; Jaffry, Murielle; Lamhaut, Lionel; Fleischel, Catherine; Aubry, Pierre

2016-08-21

Long distance running races are associated with a low risk of life-threatening events much often attributed to hypertrophic cardiomyopathy. However, retrospective analyses of aetiology lack consistency. Incidence and aetiology of life-threatening/fatal events were assessed in long distance races in the prospective Registre des Accidents Cardiaques lors des courses d'Endurance (RACE Paris Registry) from October 2006 to September 2012. Characteristics of life-threatening/fatal events were analysed by interviewing survivors and reviewing medical records including post-mortem data of each case. Seventeen life-threatening events were identified of 511 880 runners of which two were fatal. The vast majority were cardiovascular events (13/17) occurring in experienced male runners [mean (±SD) age 43 ± 10 years], with infrequent cardiovascular risk factors, atypical warning symptoms prior to the race or negative treadmill test when performed. Acute myocardial ischaemia was the predominant aetiology (8 of 13) and led to immediate myocardial revascularization. All cases with initial shockable rhythm survived. There was no difference in event rate according to marathons vs. half-marathons and events were clustered at the end of the race. A meta-analysis of all available studies including the RACE Paris registry (n = 6) demonstrated a low prevalence of life-threatening events (0.75/100 000) and that presentation with non-shockable rhythm [OR = 29.9; 95% CI (4.0-222.5), P = 0.001] or non-ischaemic aetiology [OR = 6.4; 95% CI (1.4-28.8), P = 0.015] were associated with case-fatality. Life-threatening/fatal events during long distance races are rare, most often unpredictable and mainly due to acute myocardial ischaemia. Presentation with non-shockable rhythm and non-ischaemic aetiology are the major determinant of case fatality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Intestinal coccidian parasites as an underestimated cause of travellers' diarrhoea in Polish immunocompetent patients.

PubMed

Kłudkowska, Matylda; Pielok, Łukasz; Frąckowiak, Krystyna; Paul, Małgorzata

2017-09-26

Intestinal coccidian parasites are intracellular protozoa most frequently transmitted during food-borne and water-borne infections. This group of parasites is responsible for acute diarrhoeal illnesses especially among immunocompromised patients. However, they are more frequently detected in immunocompetent individuals including travellers, and they should also be considered as important etiologic factors of travellers' diarrhoea. We examined 221 immunocompetent patients hospitalized due to acute or chronic diarrhoea and other gastrointestinal symptoms after returning from international journeys to hot climates. A basic microscopical examination and acid - fast staining of stool samples was performed. Each patient was also a part of the epidemiological investigation to define potential risk factors of tropical gastrointestinal infections. Intestinal coccidiosis was confirmed in 12 out of 221 successively hospitalized patients (5.4%). The most common coccidian parasite was Cryptosporidium spp., detected in nine Polish travellers (4.1%). Cyclospora spp. was diagnosed in three cases (1.4%), including two mixed infections with Cryptosporidium spp., and Cystoisospora spp. in two other cases (0.9%). The study has revealed that intestinal coccidian parasites are a significant threat to immunocompetent travellers and should be always considered in the differential diagnosis of gastrointestinal disorders. Therefore, it is necessary to perform specialized diagnostic methods for the detection of Cryptosporidium spp., Cystoisospora spp., and Cyclospora spp. oocysts in reference parasitology laboratories. Clinical observations demonstrated simultaneously an insufficient level of knowledge in Polish tourists concerning the main risk factors of intestinal parasitic diseases during international travels, particularly to developing countries with lower economic and sanitary conditions.

Comparison of radiography and ultrasonography for diagnosing small-intestinal mechanical obstruction in vomiting dogs.

PubMed

Sharma, Ajay; Thompson, Margret S; Scrivani, Peter V; Dykes, Nathan L; Yeager, Amy E; Freer, Sean R; Erb, Hollis N

2011-01-01

A cross-sectional study was performed on acutely vomiting dogs to compare the accuracy of radiography and ultrasonography for the diagnosis of small-intestinal mechanical obstruction and to describe several radiographic and ultrasonographic signs to identify their contribution to the final diagnosis. The sample population consisted of 82 adult dogs and small-intestinal obstruction by foreign body was confirmed in 27/82 (33%) dogs by surgery or necropsy. Radiography produced a definitive result (obstructed or not obstructed) in 58/82 (70%) of dogs; ultrasonography produced a definitive result in 80/82 (97%) of dogs. On radiographs, a diagnosis of obstruction was based on detection of segmental small-intestinal dilatation, plication, or detection of a foreign body. Approximately 30% (8/27) of obstructed dogs did not have radiographic signs of segmental small-intestinal dilatation, of which 50% (4/8) were due to linear foreign bodies. The ultrasonographic diagnosis of small-intestinal obstruction was based on detection of an obstructive lesion, sonographic signs of plication or segmental, small-intestinal dilatation. The ultrasonographic presence or absence of moderate-to-severe intestinal diameter enlargement (due to lumen dilatation) of the jejunum (>1.5 cm) was a useful discriminatory finding and, when present, should prompt a thorough search for a cause of small-intestinal obstruction. In conclusion, both abdominal radiography and abdominal ultrasonography are accurate for diagnosing small-intestinal obstruction in vomiting dogs and either may be used depending on availability and examiner choice. Abdominal ultrasonography had greater accuracy, fewer equivocal results and provided greater diagnostic confidence compared with radiography. © 2010 Veterinary Radiology & Ultrasound.

Inpatient Coronary Angiography and Revascularisation following Non-ST-Elevation Acute Coronary Syndrome in Patients with Renal Impairment: A Cohort Study Using the Myocardial Ischaemia National Audit Project

PubMed Central

Shaw, Catriona; Nitsch, Dorothea; Steenkamp, Retha; Junghans, Cornelia; Shah, Sapna; O’Donoghue, Donal; Fogarty, Damian; Weston, Clive; Sharpe, Claire C.

2014-01-01

Background International guidelines support an early invasive management strategy (including early coronary angiography and revascularisation) for non-ST-elevation acute coronary syndrome (NSTE-ACS) in patients with renal impairment. However, evidence from outside the UK suggests that this approach is underutilised. We aimed to describe practice within the NHS, and to determine whether the severity of renal dysfunction influenced the provision of angiography and modified the association between early revascularisation and survival. Methods We performed a cohort study, using multivariable logistic regression and propensity score analyses, of data from the Myocardial Ischaemia National Audit Project for patients presenting with NSTE-ACS to English or Welsh hospitals between 2008 and 2010. Findings Of 35 881 patients diagnosed with NSTE-ACS, eGFR of <60 ml/minute/1.73 m2 was present in 15 680 (43.7%). There was a stepwise decline in the odds of undergoing inpatient angiography with worsening renal dysfunction. Compared with an eGFR>90 ml/minute/1.73 m2, patients with an eGFR between 45–59 ml/minute/1.73 m2 were 33% less likely to undergo angiography (adjusted OR 0.67, 95% CI 0.55–0.81); those with an eGFR<30/minute/1.73 m2 had a 64% reduction in odds of undergoing angiography (adjusted OR 0.36, 95%CI 0.29–0.43). Of 16 646 patients who had inpatient coronary angiography, 58.5% underwent inpatient revascularisation. After adjusting for co-variables, inpatient revascularisation was associated with approximately a 30% reduction in death within 1 year compared with those managed medically after coronary angiography (adjusted OR 0.66, 95%CI 0.57–0.77), with no evidence of modification by renal function (p interaction = 0.744). Interpretation Early revascularisation may offer a similar survival benefit in patients with and without renal dysfunction, yet renal impairment is an important determinant of the provision of coronary angiography following NSTE-ACS. A

Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

DTIC Science & Technology

2016-09-01

completion of initial experiments investigating the effect of whole body and focal (GI tract) irradiation of mice on the bacterial and fungal microbiota. We...acute symptoms, will develop long-term consequences of irradiation including permanent changes to bowel function and intestinal fibrosis, which can...exposed to total body irradiation (TBI) or focal radiation to the GI tract. Timeline Status Site 1 (Stephen Shiao, MD, PhD) Site 2

[Management of Acute Type A Dissection Complicated with Acute Mesenteric Ischemia].

PubMed

Abe, Tomonobu; Usui, Akihiko

2017-07-01

Acute mesenteric ischemia as malperfusion syndrome associated with acute aortic dissection is a difficult situation. The incidence is approximately 3~4% in acute type A dissection. Traditionally, most of these patients underwent immediate simple central aortic repair expecting that mesenteric artery obstruction and intestinal ischemia would be resolved by simple central aortic repair. However, short term mortality has been reported very high in this strategy. With the aid of rapidly progressing imaging techniques and newer endovascular repair techniques, results seem to be improving in recent years. Newer management strategy include aggressive and patient specific revascularization to the mesenteric arteries, delayed central aortic repair, and meticulous intensive care. Diagnosis and management of this condition require high level of expertise. Cardiac surgeons, vascular surgeons, interventional radiologists, gastroenterologists, general surgeons, anesthesiologists, intensivists must corporate to save these patients' lives. Since this is a relatively rare condition, scientific evidence is insufficient to make robust recommendations. Further studies are warranted.

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

NASA Astrophysics Data System (ADS)

Smirnova, O. A.

2009-12-01

Mathematical models which describe the dynamics of two vital body systems (hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation are developed. These models, based on conventional biological theories, are implemented as systems of nonlinear differential equations. Their variables and constant parameters have clear biological meaning, that provides successful identification and verification of the models in hand. It is shown that the predictions of the models qualitatively and quantitatively agree with the respective experimental data for small laboratory animals (mice, rats) exposed to acute/chronic irradiation in wide ranges of doses and dose rates. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. All this bears witness to the validity of employment of the developed models, after a proper identification, in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems in various mammalian species, including humans. In particular, the models can be used for estimating effects of irradiation on astronauts in the long-term space missions, such as Lunar colonies and Mars voyages.

Effects of 1:1, 1:2 or 1:3 intra-aortic balloon counterpulsation/heart support on coronary haemodynamics and cardiac contractile efficiency in an animal model of myocardial ischaemia/reperfusion.

PubMed

Gelsomino, Sandro; Renzulli, Attilio; Rubino, Antonino S; Romano, Salvatore Mario; Lucà, Fabiana; Valente, Serafina; Gensini, Gian Franco; Lorusso, Roberto

2012-08-01

The effects of operational modes of intra-aortic balloon pumping (IABP) on coronary haemodynamics and oxygen delivery/demand ratio are unknown and were investigated in an experimental model of myocardial ischaemia reperfusion. Healthy swine (n = 24) underwent 120-minute ligation of the left anterior descending coronary artery followed by 24 h of reperfusion and were randomly assigned to have IABP 1:1 (n = 6), IABP 1:2 (n = 6), IABP 1:3 (n = 6) in the descending aorta or to no IABP implantation (n = 6) 5 min after the onset of reperfusion. Systolic (CBF(Sys)) and diastolic (CBF(Dia)) coronary blood flow, systolic (CR(Sys)) and diastolic (CR(Dia)) coronary resistances and endocardial viability ratio (EVR), as an expression of the oxygen delivery/demand ratio, were measured at 30 min, 1, 6, 12 and 24 h after coronary reperfusion, respectively. IABP at the 1:1 operational mode significantly increased CBF(Dia) and EVR, and reduced CR(Dia) throughout the experiment. Contrastingly, IABP at 1:3 mode resulted in a significant reduction in CBF(Dia), in a steady increase in CR(Dia), in a steady reduction in O(2) delivery and a constant increase in O(2) demand over time. IABP at the 1:2 mode had no overall effect on assessed parameters. IABP at the 1:1 mode enhanced coronary haemodynamics and cardiac contractile efficiency in an acute animal model of coronary ischaemia/reperfusion. On the contrary, IABP support set at the 1:2 or 1:3 modes failed to provide benefit. Progressive reduction in balloon inflation with a 1:1 mode instead of decreasing the heart/IABP operational ratio might represent a better IABP withdrawal protocol and is currently under investigation.

Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion

PubMed Central

2014-01-01

Background Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure. Methods Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion. Results Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3 ± 6.9% of initial value vs. 28.5 ± 5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0 ± 16.3% while in

Prom1 Function in Development, Intestinal Inflammation, and Intestinal Tumorigenesis

PubMed Central

Karim, Baktiar O.; Rhee, Ki-Jong; Liu, Guosheng; Yun, Kyuson; Brant, Steven R.

2014-01-01

Prom1/CD133 has been identified in colorectal, hepatocellular, and pancreatic cancer as a cancer stem cell marker and has been used as such to predict colon cancer recurrence in humans. Its potential molecular function as well as its role as a marker of intestinal regeneration is still not fully known. We evaluated the role of Prom1 in intestinal regeneration in inflammatory bowel disease (IBD), determined the function of Prom1, and characterized the effect of a lack of Prom1 on intestinal tumor formation in animal models. Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas. Also, Prom1 knockout mice are more susceptible to intestinal tumor formation. We conclude that Prom1 likely plays a role in regulating intestinal homeostasis and that these results clearly illustrate the role of Prom1 in intestinal regeneration. We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer. PMID:25452936

Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

PubMed

Cursio, R; Filippa, N; Miele, C; Van Obberghen, E; Gugenheim, J

2006-06-01

This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Targeting Iron Homeostasis in Acute Kidney Injury

PubMed Central

Walker, Vyvyca J.; Agarwal, Anupam

2017-01-01

Summary Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron’s ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice.

PubMed

Samuels, S E; Knowles, A L; Tilignac, T; Debiton, E; Madelmont, J C; Attaix, D

2000-09-01

The impact of cancer cachexia and chemotherapy on small intestinal protein metabolism and its subsequent recovery was investigated. Cancer cachexia was induced in mice with colon 26 adenocarcinoma, which is a small and slow-growing tumor characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12ClN3O4S). Both healthy mice and tumor-bearing mice were given a single i.p. injection of cystemustine (20 mg/kg) 3 days after the onset of cachexia. Cancer cachexia led to a reduced in vivo rate of protein synthesis in the small intestine relative to healthy mice (-13 to -34%; P < 0.05), resulting in a 25% loss of protein mass (P < 0.05), and decreased villus width and crypt depth (P < 0.05). In treated mice, acute cytotoxicity of chemotherapy did not promote further wasting of small intestinal protein mass, nor did it result in further damage to intestinal morphology. In contrast, mucosal damage and a 17% reduction in small intestinal protein mass (P < 0.05) were evident in healthy mice treated with cystemustine, suggesting that the effects of chemotherapy on the small intestine in a state of cancer cachexia are not additive, which was an unexpected finding. Complete and rapid recovery of small intestinal protein mass in cured mice resulted from an increase in the rate of protein synthesis compared with healthy mice (23-34%; P < 0.05). Northern hybridizations of mRNA encoding components of the major proteolytic systems suggested that proteolysis may not have mediated intestinal wasting or recovery. A major clinical goal should be to design methods to improve small intestinal protein metabolism before the initiation of chemotherapy.

Small intestinal ischemia and infarction

MedlinePlus

Intestinal necrosis; Ischemic bowel - small intestine; Dead bowel - small intestine; Dead gut - small intestine; Infarcted bowel - small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine

Keratins Are Altered in Intestinal Disease-Related Stress Responses

PubMed Central

Helenius, Terhi O.; Antman, Cecilia A.; Asghar, Muhammad Nadeem; Nyström, Joel H.; Toivola, Diana M.

2016-01-01

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. PMID:27626448

Keratins Are Altered in Intestinal Disease-Related Stress Responses.

PubMed

Helenius, Terhi O; Antman, Cecilia A; Asghar, Muhammad Nadeem; Nyström, Joel H; Toivola, Diana M

2016-09-10

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.

Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection.

PubMed

Brown, Judy J; Short, Sarah P; Stencel-Baerenwald, Jennifer; Urbanek, Kelly; Pruijssers, Andrea J; McAllister, Nicole; Ikizler, Mine; Taylor, Gwen; Aravamudhan, Pavithra; Khomandiak, Solomiia; Jabri, Bana; Williams, Christopher S; Dermody, Terence S

2018-05-15

Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine. Compared with T1L, T3D-RV infection triggered apoptosis of intestinal epithelial cells and subsequent sloughing of dead cells into the intestinal lumen. We conclude that the infection advantage of T1L derives from its capacity to subvert host restriction by epithelial cell apoptosis, providing a possible mechanism by which T1L enhances inflammatory signals during antigen feeding. Using a panel of T1L × T3D-RV reassortant viruses, we identified the viral M1 and M2 gene segments as determinants of reovirus-induced apoptosis in the intestine. Expression of the T1L M1 and M2 genes in a T3D-RV background was sufficient to limit epithelial cell apoptosis and enhance viral infection to levels displayed by T1L. These findings define additional reovirus gene segments required for enteric infection of mice and illuminate the antiviral effect of intestinal epithelial cell apoptosis in limiting enteric viral infection. Viral strain-specific differences in the capacity to infect the intestine may be useful in identifying viruses capable of ameliorating tolerance to fed antigen in autoimmune conditions like celiac disease. IMPORTANCE Acute viral infections are thought to be cleared by the host with few lasting consequences. However, there may be much broader and long-lasting effects of viruses on immune homeostasis. Infection with reovirus, a common, nonpathogenic virus, triggers inflammation against innocuous food antigens

Impact of Intestinal Microbiota on Intestinal Luminal Metabolome

PubMed Central

Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

2012-01-01

Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p < 0.05), 77 metabolites were present in significantly lower concentrations and/or incidence in the GF mice than in the Ex-GF mice (p < 0.05), and 56 metabolites showed no differences in the concentration or incidence between GF and Ex-GF mice. These indicate that intestinal microbiota highly influenced the colonic luminal metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057

Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.

PubMed

Ejaz, Sohail; Emmrich, Julius V; Sitnikov, Sergey L; Hong, Young T; Sawiak, Stephen J; Fryer, Tim D; Aigbirhio, Franklin I; Williamson, David J; Baron, Jean-Claude

2016-03-01

'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack

Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases

PubMed Central

Gil-Campos, Mercedes

2018-01-01

The pediatric population is continually at risk of developing infectious and inflammatory diseases. The treatment for infections, particularly gastrointestinal conditions, focuses on oral or intravenous rehydration, nutritional support and, in certain case, antibiotics. Over the past decade, the probiotics and synbiotics administration for the prevention and treatment of different acute and chronic infectious diseases has dramatically increased. Probiotic microorganisms are primarily used as treatments because they can stimulate changes in the intestinal microbial ecosystem and improve the immunological status of the host. The beneficial impact of probiotics is mediated by different mechanisms. These mechanisms include the probiotics’ capacity to increase the intestinal barrier function, to prevent bacterial transferation and to modulate inflammation through immune receptor cascade signaling, as well as their ability to regulate the expression of selected host intestinal genes. Nevertheless, with respect to pediatric intestinal diseases, information pertaining to these key mechanisms of action is scarce, particularly for immune-mediated mechanisms of action. In the present work, we review the biochemical and molecular mechanisms of action of probiotics and synbiotics that affect the immune system. PMID:29303974

Extra-adrenal glucocorticoid synthesis in the intestinal epithelium: more than a drop in the ocean?

PubMed

Noti, Mario; Sidler, Daniel; Brunner, Thomas

2009-07-01

Glucocorticoids (GC) are lipophilic hormones commonly used as therapeutics in acute and chronic inflammatory disorders such as inflammatory bowel disease due to their attributed anti-inflammatory and immunosuppressive actions. Although the adrenal glands are the major source of endogenous GC, there is increasing evidence for the production of extra-adrenal GC in the brain, thymus, skin, vasculature, and the intestine. However, the physiological relevance of extra-adrenal-produced GC remains still ambiguous. Therefore, this review attracts attention to discuss possible biological benefits of extra-adrenal-synthesized GC, especially focusing on the impact of locally synthesized GC in the regulation of intestinal immune responses.

The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP).

PubMed

Zaman, M Justin; Stirling, Susan; Shepstone, Lee; Ryding, Alisdair; Flather, Marcus; Bachmann, Max; Myint, Phyo Kyaw

2014-06-14

Older people increasingly constitute a large proportion of the acute coronary syndrome (ACS) population. We examined the relationship of age with receipt of more intensive management and secondary prevention medicine. Then, the comparative association of intensive management (reperfusion/angiography) over a conservative strategy on time to death was investigated by age. Using data from 155 818 patients in the national registry for ACS in England and Wales [the Myocardial Ischaemia National Audit Project (MINAP)], we found that older patients were incrementally less likely to receive secondary prevention medicines and intensive management for both ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In STEMI patients ≥85 years, 55% received reperfusion compared with 84% in those aged 18 to <65 [odds ratio 0.22 (95% CI 0.21, 0.24)]. Not receiving intensive management was associated with worse survival [mean follow-up 2.29 years (SD 1.42)] in all age groups (adjusted for sex, cardiovascular risk factors, co-morbidities, healthcare factors, and case severity), but there was an incremental reduction in survival benefit from intensive management with increasing age. In STEMI patients aged 18-64, 65-74, 75-84, and ≥85, adjusted hazard ratios (HRs) for all-cause mortality comparing conservative treatment to intensive management were 1.98 (1.78, 2.19), 1.65 (1.51, 1.80), 1.62 (1.52, 1.72), and 1.36 (1.27, 1.47), respectively. In NSTEMI patients, the respective HRs were 4.37 (4.00, 4.78), 3.76 (3.54, 3.99), 2.79 (2.67, 2.91), and 1.90 (1.77, 2.04). We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS. Published on behalf of

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

PubMed

Lai, Yu; Zhong, Wa; Yu, Tao; Xia, Zhong-Sheng; Li, Jie-Yao; Ouyang, Hui; Shan, Ti-Dong; Yang, Hong-Sheng; Chen, Qi-Kui

2015-01-01

The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

PubMed Central

Yu, Tao; Xia, Zhong-Sheng; Li, Jie-Yao; Ouyang, Hui; Shan, Ti-Dong; Yang, Hong-Sheng; Chen, Qi-Kui

2015-01-01

Background The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. Methods BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. Results COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Conclusion Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin. PMID:26135128

Late intestinal obstruction due to an intestinal volvulus in a pregnant patient with a previous Roux-en-Y gastric bypass.

PubMed

Gazzalle, Anajara; Braun, Débora; Cavazzola, Leandro Totti; Wendt, Luiz Roberto; Navarini, Daniel; Fauri, Marcelo de Azevedo; Vitola, Santo Pascual

2010-12-01

This is a case of a 33 weeks pregnant woman, presented 2 years after laparoscopic Roux-en-Y gastric bypass, with abdominal pain for 2 days. A laparoscopic cholecystectomy was performed 1 day earlier in another hospital, without improving the pain. She presented at our hospital with acute abdominal pain and clinical signs of intestinal obstruction, undergoing an exploratory laparotomy that revealed a volvulus and necrosis of the jejunum from the gastroenteroanastomosis through the lateral enteroenterostomy, which was resected with the reconstruction of the Roux-en-Y limb performed at the same operation. Patient and neonate presented with improvement after surgery and the patient was discharged on postoperative day 15. Internal hernias after bariatric surgery have been reported as the cause of acute abdomen problems during pregnancy, which may progress to necrosis and perforation. The delay of surgical intervention could have brought a tragic outcome for mother and neonate.

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

[The intestinal microflora of persons subjected to a radiation lesion].

PubMed

Sudenko, V I; Nagornaia, S S; Groma, L I

1992-01-01

The content of large intestine has been studied in persons exposed to radiation injury in consequence of the accident at the Chernobyl Atomic Power Plant. It is stated that bifidobacteria (10(7)-10(10) cells in 1 g of feces) prevailed (as in healthy people), Bifidobacterium indicum being a dominating species. Amount of lactic-acid bacteria in 1 g of defecations of examined patients was within the range of 10(6)-10(9) cells and in certain persons it reached 10(10) cells (primarily fecal Enterococci). A considerable amount of patients with acute radiation sickness of the 3d degree had in their intestine 10(9)/g of lactic-acid bacteria, Lactobacillus casei and L. plantarum prevailing there. The frequency of yeast isolation from defecations of patients constituted 83%, while the number of cells in 1 g of feces--from 10 to 10(4). Yeast of the Candida genus, mainly Candida parapsilosis, prevailed. The species composition of isolated microorganisms has no substantial differences from microcenosis of healthy people. The content of intestine of persons suffered from radiation is characterized only by greater amount of lactic-acid bacteria and enterococci as compared with healthy adults.

Intestinal Perforation Due to Foreign Body Ingestion in a Schizophrenic Patient

PubMed Central

Zarei, Mina; Shariati, Behnam; Bidaki, Reza

2016-01-01

Introduction Ingestion of foreign bodies has been previously reported in some patients with schizophrenia. This behavior may be a manifestation of delusional beliefs or a response to command hallucinations and can lead to severe complications. Case Presentation This paper reports a patient with schizophrenia who, as a manifestation of his illness, ingested a metallic skewer to kill ademon inside his abdomen that he believed was controlling him. As a result, he developed an acute intestinal perforation and underwent surgery. Conclusions It is of a great importance to closely monitor the therapy compliance of patients suffering from mental illnesses. This will benefit them by preventing some of the serious complications of their disease, which may include life-threatening conditions such as intestinal perforation that needs surgical intervention. PMID:27803892

[A Case of Intestinal Obstruction Caused by a Bezoar after Pylous-Preserving Gastrectomy].

PubMed

Yamazato, Yuzo; Kosuga, Toshiyuki; Ichikawa, Daisuke; Kubota, Takeshi; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Arita, Tomohiro; Morimura, Ryo; Murayama, Yasutoshi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Otsuji, Eigo

2017-11-01

A 65-year-old woman with a history of pylorus-preserving gastrectomy(PPG)for early gastric cancer visited our hospital because of vomiting. Gastrointestinal endoscopy revealed a large bezoar in the anastomotic site of the stomach. Because the bezoar was too large to be collected orally, the dissolution therapy with taking Coca-Cola®was continued. On the 3rd day after hospitalization, she felt acute abdominal pain with vomiting. Computed tomography revealed intestinal obstruction by a mass with air bubbles inside in the ileum. Emergency operation was performed under a diagnosis of intestinal obstruction due to the bezoar. The black brown bezoar sized 80×35×30mm was extracted through an ileotomy. The delayed gastric empty is considered to involve in the bezoar formation. Therefore, the appropriate education of diet and periodic endoscopic screening are necessary for patients with large amounts of gastric residues especially after PPG. In the dissolution therapy, physicians need to be careful of intestinal obstruction by a bezoar.

MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6.

PubMed

Wang, Xiaohui; Ha, Tuanzhu; Zou, Jianghuan; Ren, Danyang; Liu, Li; Zhang, Xia; Kalbfleisch, John; Gao, Xiang; Williams, David; Li, Chuanfu

2014-06-01

The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Renal sympathetic denervation modulates ventricular electrophysiology and has a protective effect on ischaemia-induced ventricular arrhythmia.

PubMed

Huang, Bing; Yu, Lilei; He, Bo; Lu, Zhibing; Wang, Songyun; He, Wenbo; Yang, Kang; Liao, Kai; Zhang, Ling; Jiang, Hong

2014-11-01

Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear. Thirty-three mongrel dogs were included in the present study. Renal sympathetic denervation was performed by radiofrequency ablation of the adventitial surface of the renal artery. In group 1 (n = 8), programmed stimulation was performed before and after RSD to determine the ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. The same parameters were measured in five other animals that underwent sham RSD to serve as controls. In group 2 (n = 10), acute myocardial ischaemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD, and the incidence of ventricular arrhythmia (VA) was calculated during 1 h of recording. In another 10 dogs (group 3), AMI was induced and VA was measured with sham RSD. In group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximal slope (Smax) of the restitution curve and suppressed APD alternans at each site. Renal sympathetic denervation also significantly decreased the spatial dispersion of ERP, APD and Smax. In the five control animals, no significant electrophysiological change was detected after sham RSD. The occurrence of spontaneous VA during 1 h of AMI in group 2 was significantly lower than that in group 3. These data suggest that RSD stabilizes ventricular electrophysiological properties in normal hearts and reduces the occurrence of VA in hearts experiencing AMI. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Human intestinal anisakiosis due to consumption of raw salmon.

PubMed

Couture, Christian; Measures, Lena; Gagnon, Joël; Desbiens, Christine

2003-08-01

Anisakiosis is a parasitic infection that follows consumption of raw or insufficiently pickled, salted, smoked, or cooked wild marine fish infected with Anisakis sp. larvae. We report a case of intestinal anisakiosis in a 50-year-old man from Quebec who presented with abdominal pain and peripheral eosinophilia after eating raw wild-caught salmon from the Pacific Ocean off Canada. Abdominal CT scan showed bowel distension proximal to a segmental jejunal wall thickening, which was resected. The jejunum segment showed a localized area of serositis with mucosal edema and a submucosal abscess rich in eosinophils surrounding a parasite consistent with the third larval stage of Anisakis sp. Diagnostic morphologic characteristics included an unpaired excretory gland (renette cell), Y-shaped lateral epidermal cords, no apparent reproductive system, and a ventriculus (glandular esophagus). These features and the absence of lateral alae excluded Ascaris sp. The absence of ventricular appendage and intestinal cecum excluded other anisakids of the genera Pseudoterranova and Contracaecum. As the popularity of eating raw fish is growing in North America, anisakiosis may be diagnosed more frequently in surgical specimens. This parasitic infection should be considered in the differential diagnosis of acute abdominal syndromes and eosinophilic infiltrates of the stomach, small intestine, colon, omentum, and mesentery, especially with a history of raw marine fish consumption.

[Intestinal occlusion by persistence of the omphalo-enteric conduct in a 10-year old child].

PubMed

Filip, F; Goţia, D G; Aprodu, S G; Vlad, A; Savu, A; Savu, B; Bejenaru, T

2000-01-01

The persistence of the omphalo-enteric conduct is a rare, but possible, cause of pathology in children. Haemorrhage and intestinal occlusion are the most frequent clinical presentations, usually in infants. We describe the case of a 10 year old boy, who was admitted in our department for what seemed first to be an acute appendicitis. During hospitalization, the clinical picture turned on to an intestinal occlusion, and the patient finally required surgery. We performed exploratory laparotomy and we discovered a mechanical occlusion by persistence of the omphalo-enteric conduct, which was treated according to standard protocols. The post-operative course was good, and the child was discharged 8 days after surgery. This case emphasizes that the persistence of the omphalo-enteric conduct should be sought as the source of symptoms in any child presenting with intestinal occlusion.

ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults.

PubMed

Pironi, Loris; Arends, Jann; Baxter, Janet; Bozzetti, Federico; Peláez, Rosa Burgos; Cuerda, Cristina; Forbes, Alastair; Gabe, Simon; Gillanders, Lyn; Holst, Mette; Jeppesen, Palle Bekker; Joly, Francisca; Kelly, Darlene; Klek, Stanislaw; Irtun, Øivind; Olde Damink, S W; Panisic, Marina; Rasmussen, Henrik Højgaard; Staun, Michael; Szczepanek, Kinga; Van Gossum, André; Wanten, Geert; Schneider, Stéphane Michel; Shaffer, Jon

2015-04-01

Intestinal failure (IF) is not included in the list of PubMed Mesh terms, as failure is the term describing a state of non functioning of other organs, and as such is not well recognized. No scientific society has yet devised a formal definition and classification of IF. The European Society for Clinical Nutrition and Metabolism guideline committee endorsed its "home artificial nutrition and chronic IF" and "acute IF" special interest groups to write recommendations on these issues. After a Medline Search, in December 2013, for "intestinal failure" and "review"[Publication Type], the project was developed using the Delphi round methodology. The final consensus was reached on March 2014, after 5 Delphi rounds and two live meetings. The recommendations comprise the definition of IF, a functional and a pathophysiological classification for both acute and chronic IF and a clinical classification of chronic IF. IF was defined as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth". This formal definition and classification of IF, will facilitate communication and cooperation among professionals in clinical practice, organization and management, and research. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

PubMed

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

An Intestinal "Transformers"-like Nanocarrier System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs.

PubMed

Chuang, Er-Yuan; Lin, Kun-Ju; Huang, Tring-Yo; Chen, Hsin-Lung; Miao, Yang-Bao; Lin, Po-Yen; Chen, Chiung-Tong; Juang, Jyuhn-Huarng; Sung, Hsing-Wen

2018-06-06

Increasing the intestinal dissolution of orally administered poorly water-soluble drugs that have poor oral bioavailability to a therapeutically effective level has long been an elusive goal. In this work, an approach that can greatly enhance the oral bioavailability of a poorly water-soluble drug such as curcumin (CUR) is developed, using a "Transformers"-like nanocarrier system (TLNS) that can self-emulsify the drug molecules in the intestinal lumen to form nanoemulsions. Owing to its known anti-inflammation activity, the use of CUR in treating pancreatitis is evaluated herein. Structural changes of the TLNS in the intestinal environment to form the CUR-laden nanoemulsions are confirmed in vitro. The therapeutic efficacy of this TLNS is evaluated in rats with experimentally induced acute pancreatitis (AP). Notably, the CUR-laden nanoemulsions that are obtained using the proposed TLNS can passively target intestinal M cells, in which they are transcytosed and then transported into the pancreatic tissues via the intestinal lymphatic system. The pancreases in rats that are treated with the TLNS yield approximately 12 times stronger CUR signals than their counterparts receiving free CUR, potentially improving the recovery of AP. These findings demonstrate that the proposed TLNS can markedly increase the intestinal drug dissolution, making oral delivery a favorable noninvasive means of administering poorly water-soluble drugs.

[The acute (surgical) abdomen - epidemiology, diagnosis and general principles of management].

PubMed

Grundmann, R T; Petersen, M; Lippert, H; Meyer, F

2010-06-01

This review comments on epidemiology, diagnosis and general principles of surgical management in patients with acute abdomen. DEFINITION AND EPIDEMIOLOGY: The most common cause of acute abdominal pain is non-specific abdominal pain (24 - 44.3 % of the study populations), followed by acute appendicitis (15.9 - 28.1 %), acute biliary disease (2.9 - 9.7 %) and bowel obstruction or diverticulitits in elderly patients. Acute appendicitis represents the cause of surgical intervention in two-thirds of the children with acute abdomen. A standardised physical examination combined with ultrasonography (US) represents the initial investigation in patients with acute abdominal pain. Due to the risk associated with radiation and due to the costs, a selective use of CT imaging is recommended. The work-flow given in this paper restricts the use of CT imaging to less than 50 % of patients with acute abdominal pain. Diagnostic laparoscopy should be considered in patients without a specific diagnosis after appropriate imaging and as an alternative to active clinical observation which is the current practice in patients with non-specific abdominal pain. Acute small bowel obstruction has previously been considered as a relative contraindication for laparoscopic management, but it has been shown in the meantime that laparoscopic treatment is an elegant tool for the management of simple band small bowel obstruction. Bedside diagnostic laparoscopy is recommended in intensive care unit (ICU) patients with acute abdomen or sepsis of unknown origin, in suspicion of acute cholecystitis, diffuse gut hypoperfusion and mesenteric ischaemia or in refractory lactic acidosis, especially after cardiac surgery. Early administration of analgesia to patients with acute abdominal pain in the emergency department will reduce the patient's discomfort without impairing clinically important diagnostic accuracy and is recommended on the basis of some prospective randomised trials. However, the impact on

Seasonal variation of acute gastro-intestinal illness by hydroclimatic regime and drinking water source: a retrospective population-based study.

PubMed

Galway, Lindsay P; Allen, Diana M; Parkes, Margot W; Takaro, Tim K

2014-03-01

Acute gastro-intestinal illness (AGI) is a major cause of mortality and morbidity worldwide and an important public health problem. Despite the fact that AGI is currently responsible for a huge burden of disease throughout the world, important knowledge gaps exist in terms of its epidemiology. Specifically, an understanding of seasonality and those factors driving seasonal variation remain elusive. This paper aims to assess variation in the incidence of AGI in British Columbia (BC), Canada over an 11-year study period. We assessed variation in AGI dynamics in general, and disaggregated by hydroclimatic regime and drinking water source. We used several different visual and statistical techniques to describe and characterize seasonal and annual patterns in AGI incidence over time. Our results consistently illustrate marked seasonal patterns; seasonality remains when the dataset is disaggregated by hydroclimatic regime and drinking water source; however, differences in the magnitude and timing of the peaks and troughs are noted. We conclude that systematic descriptions of infectious illness dynamics over time is a valuable tool for informing disease prevention strategies and generating hypotheses to guide future research in an era of global environmental change.

Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms.

PubMed

Ghosal, Abhisek; Jellbauer, Stefan; Kapadia, Rubina; Raffatellu, Manuela; Said, Hamid M

2015-07-15

Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines.

Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms

PubMed Central

Ghosal, Abhisek; Jellbauer, Stefan; Kapadia, Rubina; Raffatellu, Manuela

2015-01-01

Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines. PMID:25999427

Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

PubMed

Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

2017-11-01

In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

Lipopolysaccharide Binding Protein Enables Intestinal Epithelial Restitution Despite Lipopolysaccharide Exposure

PubMed Central

Richter, Juli M.; Schanbacher, Brandon L.; Huang, Hong; Xue, Jianjing; Bauer, John A.; Giannone, Peter J.

2011-01-01

development of intestinal injury when given during our rodent model of NEC. Abnormal bacterial colonization and activation of innate immunity by LPS are likely involved in the pathogenesis of NEC. The attentuation of wound healing was reversed when LBP was added to LPS but only in the higher concentrations. At these same concentrations of LBP, TLR4 was decreased to that of control. These results indicate that LBP may be a novel therapeutic strategy to facilitate wound healing after the acute phase of NEC and other forms of intestinal injury. PMID:22002480

Immune cell inflammatory cytokine responses differ between central and systemic compartments in response to acute exercise in mice.

PubMed

Pervaiz, Nabeel; Hoffman-Goetz, Laurie

2012-01-01

Exhaustive exercise induces apoptosis and oxidative stress in systemic organs and tissues and is associated with increased levels of pro-inflammatory cytokines. The effects of acute exercise on cytokine expression and apoptosis of immune cells in the central nervous system (CNS) have not been well characterized. We investigated the effects of a single bout of strenuous exercise on the expression of TNF-alpha, IL-6, and IL-beta, as well as the apoptotic status of cells in the hippocampus of healthy mice. To compare central vs. systemic differences, cytokine expression in the intestinal lymphocytes of a subset of mice were also assessed. Female C57BL/6 mice were divided into three groups: sedentary controls (NOTREAD) (n = 22), treadmill exercise with immediate sacrifice (TREAD-Imm) (n = 21), or treadmill exercise with sacrifice after 2 hours (TREAD-2h). TNF-alpha, IL-6, and IL-1beta expression in the hippocampus and intestinal lymphocytes were measured by Western blot analysis. Percentages of hippocampal cells undergoing apoptosis (Annexin+) or necrosis (Propidium Iodide+) were determined through flow cytometry. Plasma levels of 8-isoprostane and corticosterone were measured using commercially available EIA kits. Acute treadmill exercise led to significant decreases in TNF-alpha (p<0.05) and increases in IL-6 (p<0.05) expression in the hippocampus of healthy mice. No effects of acute exercise on the apoptotic status of hippocampal cells were observed. In intestinal lymphocytes, the exercise bout led to significant increases in TNF-alpha (p<0.05), IL-6 (p<0.05), and IL-1beta (p<0.05). Acute exercise was associated with a significant increase in both plasma 8-isoprostane (p<0.05) and corticosterone (p<0.05) levels. Acute exercise differentially affects the pattern ofpro-inflammatory cytokine expression in the hippocampus compared to intestinal lymphocytes and, further, does not induce apoptosis in hippocampal cells.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

PubMed

Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

2017-04-01

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.

PubMed

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-04-01

Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides , Enterobacteriaceae , Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae , Lactobacillaceae , Clostridiaceae , Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.

The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

PubMed

Suchodolski, Jan S; Markel, Melissa E; Garcia-Mazcorro, Jose F; Unterer, Stefan; Heilmann, Romy M; Dowd, Scot E; Kachroo, Priyanka; Ivanov, Ivan; Minamoto, Yasushi; Dillman, Enricka M; Steiner, Jörg M; Cook, Audrey K; Toresson, Linda

2012-01-01

Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes.

The Fecal Microbiome in Dogs with Acute Diarrhea and Idiopathic Inflammatory Bowel Disease

PubMed Central

Suchodolski, Jan S.; Markel, Melissa E.; Garcia-Mazcorro, Jose F.; Unterer, Stefan; Heilmann, Romy M.; Dowd, Scot E.; Kachroo, Priyanka; Ivanov, Ivan; Minamoto, Yasushi; Dillman, Enricka M.; Steiner, Jörg M.; Cook, Audrey K.; Toresson, Linda

2012-01-01

Background Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Methodology/Principal Findings Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Conclusions Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal

The acute gastrointestinal subsyndrome of the acute radiation syndrome: a rhesus macaque model.

PubMed

MacVittie, Thomas J; Farese, Ann M; Bennett, Alexander; Gelfond, Daniel; Shea-Donohue, Terez; Tudor, Gregory; Booth, Catherine; McFarland, Emylee; Jackson, William

2012-10-01

The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of

The effect of butorphanol postconditioning on myocardial ischaemia reperfusion injury in rats

PubMed Central

Wu, Yun; Wan, Jing; Zhen, Wen-Zhon; Chen, Liu-Fang; Zhan, Jia; Ke, Jian-Juan; Zhang,, Zong-Ze; Wang, Yan-Lin

2014-01-01

OBJECTIVES Butorphanol tartrate is a synthetic opioid partial agonist analgesic. Butorphanol targets the heart, mainly via κ-opioid receptor (κ-OR) activation. The purpose of this study was to determine the effect and mechanism underlying butorphanol postconditioning (B-Post) on myocardial ischaemia reperfusion injury in rats. METHODS Seventy-five male Sprague–Dawley rats were randomly divided into five groups of 15 each: Group sham; Group I/R (ischaemia/reperfusion); Group B (butorphanol postconditioning); Group B/N (butorphanol postconditioning + antagonist of κ-OR nor-binaltorphimine [Nor-BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive potassium (KATP) channel blocker glibenclamide [GLI]). The left coronary anterior descending artery (LAD) was occluded for 30 min, followed by a 120-min reperfusion. Blood samples were obtained at the end of reperfusion for determination of serum tumour necrosis factor (TNF)-α and interleukin (IL)-6 concentrations. The hearts were then excised for determination of myocardial infarct size by triphenyltetrazolium chloride staining. The myocardial tissues were used for determination of the expression of myocardial superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO). RESULTS Myocardial infarct size was significantly reduced in B (26.4 ± 1.83%), B/N (34.5 ± 1.56%) and B/G (31.5 ± 1.27%) Groups compared with Group I/R (46.8 ± 1.41%) (all P < 0. 001). The serum TNF-α and IL-6 concentrations and the MDA and MPO activities in the ischaemic area in B, B/N and B/G Groups were significantly lower than those in the I/R Group (all P < 0.001). In addition, myocardial infarct size, TNF-α and IL-6 concentrations and the MDA and MPO activities in B/N and B/G Groups were higher than those in the B Group (all P < 0.001). In contrast, SOD activity was significantly increased in B, B/N and B/G Groups, and SOD activity in B/N and B/G Groups was less than in the B Group (all P < 0

Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia-reperfusion injury model treated with sildenafil citrate.

PubMed

Zanoni, Diogo S; Da Silva, Germana A; Ezra-Elia, Raaya; Carvalho, Márcio; Quitzan, Juliany G; Ofri, Ron; Laus, José L; Laufer-Amorim, Renee

2017-06-01

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia-reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (n = 6) and two experimentally induced ischaemia-reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia-reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet ® ). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT-PCR for expression of Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. Sildenafil-treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo-treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase-7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase-6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro-apoptotic factors and decrease in the anti-apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression

Intestinal M cells

PubMed Central

Ohno, Hiroshi

2016-01-01

We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer’s patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions. PMID:26634447

Caecal volvulus: a consequence of acute cholecystitis

PubMed Central

Anjum, Ghulam Ali; Jaberansari, Sarah; Habeeb, Kayode

2013-01-01

Caecal volvulus is an uncommon cause of closed loop intestinal obstruction which can lead to caecal gangrene and high mortality. Delay in diagnosis is one of the causes of this high mortality. Caecal volvulus is reported to be associated with previous abdominal surgery in most cases. We present the first reported case of caecal volvulus following/associated with acute cholecystitis. PMID:23749828

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

PubMed Central

de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

2017-01-01

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids

PubMed Central

Di Rienzi, Sara C; Jacobson, Juliet; Kennedy, Elizabeth A; Bell, Mary E; Shi, Qiaojuan; Waters, Jillian L; Lawrence, Peter; Brenna, J Thomas; Britton, Robert A; Walter, Jens

2018-01-01

Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary changes may have impacted their ecology is unclear. Here, we compared the in vitro and in vivo effects of 18:2 on Lactobacillus reuteri and L. johnsonii. Directed evolution in vitro in both species led to strong 18:2 resistance with mutations in genes for lipid biosynthesis, acid stress, and the cell membrane or wall. Small-intestinal Lactobacillus populations in mice were unaffected by chronic and acute 18:2 exposure, yet harbored both 18:2- sensitive and resistant strains. This work shows that extant small intestinal lactobacilli are protected from toxic dietary components via the gut environment as well as their own capacity to evolve resistance. PMID:29580380

Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden.

PubMed

Cervin, A; Tjärnström, J; Ravn, H; Acosta, S; Hultgren, R; Welander, M; Björck, M

2015-09-01

Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaemia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, <.001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and <.001), and with a posterior approach in 20.8% (121/581). The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics. Copyright © 2015 The Authors

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

PubMed

Axelsson, B; Johansson, G; Abrahamsson, P; Gupta, A; Tydén, H; Wouters, P; Haney, M

2013-07-01

Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Spectral analysis of bowel sounds in intestinal obstruction using an electronic stethoscope.

PubMed

Ching, Siok Siong; Tan, Yih Kai

2012-09-07

To determine the value of bowel sounds analysis using an electronic stethoscope to support a clinical diagnosis of intestinal obstruction. Subjects were patients who presented with a diagnosis of possible intestinal obstruction based on symptoms, signs, and radiological findings. A 3M™ Littmann(®) Model 4100 electronic stethoscope was used in this study. With the patients lying supine, six 8-second recordings of bowel sounds were taken from each patient from the lower abdomen. The recordings were analysed for sound duration, sound-to-sound interval, dominant frequency, and peak frequency. Clinical and radiological data were reviewed and the patients were classified as having either acute, subacute, or no bowel obstruction. Comparison of bowel sound characteristics was made between these subgroups of patients. In the presence of an obstruction, the site of obstruction was identified and bowel calibre was also measured to correlate with bowel sounds. A total of 71 patients were studied during the period July 2009 to January 2011. Forty patients had acute bowel obstruction (27 small bowel obstruction and 13 large bowel obstruction), 11 had subacute bowel obstruction (eight in the small bowel and three in large bowel) and 20 had no bowel obstruction (diagnoses of other conditions were made). Twenty-five patients received surgical intervention (35.2%) during the same admission for acute abdominal conditions. A total of 426 recordings were made and 420 recordings were used for analysis. There was no significant difference in sound-to-sound interval, dominant frequency, and peak frequency among patients with acute bowel obstruction, subacute bowel obstruction, and no bowel obstruction. In acute large bowel obstruction, the sound duration was significantly longer (median 0.81 s vs 0.55 s, P = 0.021) and the dominant frequency was significantly higher (median 440 Hz vs 288 Hz, P = 0.003) when compared to acute small bowel obstruction. No significant difference was seen

Spectral analysis of bowel sounds in intestinal obstruction using an electronic stethoscope

PubMed Central

Ching, Siok Siong; Tan, Yih Kai

2012-01-01

AIM: To determine the value of bowel sounds analysis using an electronic stethoscope to support a clinical diagnosis of intestinal obstruction. METHODS: Subjects were patients who presented with a diagnosis of possible intestinal obstruction based on symptoms, signs, and radiological findings. A 3M™ Littmann® Model 4100 electronic stethoscope was used in this study. With the patients lying supine, six 8-second recordings of bowel sounds were taken from each patient from the lower abdomen. The recordings were analysed for sound duration, sound-to-sound interval, dominant frequency, and peak frequency. Clinical and radiological data were reviewed and the patients were classified as having either acute, subacute, or no bowel obstruction. Comparison of bowel sound characteristics was made between these subgroups of patients. In the presence of an obstruction, the site of obstruction was identified and bowel calibre was also measured to correlate with bowel sounds. RESULTS: A total of 71 patients were studied during the period July 2009 to January 2011. Forty patients had acute bowel obstruction (27 small bowel obstruction and 13 large bowel obstruction), 11 had subacute bowel obstruction (eight in the small bowel and three in large bowel) and 20 had no bowel obstruction (diagnoses of other conditions were made). Twenty-five patients received surgical intervention (35.2%) during the same admission for acute abdominal conditions. A total of 426 recordings were made and 420 recordings were used for analysis. There was no significant difference in sound-to-sound interval, dominant frequency, and peak frequency among patients with acute bowel obstruction, subacute bowel obstruction, and no bowel obstruction. In acute large bowel obstruction, the sound duration was significantly longer (median 0.81 s vs 0.55 s, P = 0.021) and the dominant frequency was significantly higher (median 440 Hz vs 288 Hz, P = 0.003) when compared to acute small bowel obstruction. No significant

Diagnosis and interpretation of intestinal dysbiosis in dogs and cats.

PubMed

Suchodolski, Jan S

2016-09-01

The intestinal tracts of dogs and cats harbor a highly complex microbiota, which consists of bacteria, fungi, viruses and protozoa. Until recently, traditional bacterial culture was commonly used to identify bacteria present in the gastrointestinal tract, but it is now well recognized that standard plating techniques do not have enough resolution for identification of the mostly anaerobic bacteria that reside within the gut. Molecular methods are now established for assessing intestinal dysbiosis in dogs and cats with gastrointestinal disease, but these approaches are not yet widely available for routine diagnosis. The loss of normal commensal bacterial microbiota (i.e. Lachnospiraceae, Ruminococcaceae, and Faecalibacterium spp.) in acute and chronic intestinal diseases has been linked to metabolic changes, for example alterations in immunomodulatory bacterial metabolites, such as short chain fatty acids and secondary bile acids. This highlights the importance of dysbiosis in the pathophysiology of gastrointestinal diseases. Development of molecular based assays for specific bacterial groups, calculations of microbial dysbiosis indices and assays for microbial functional metabolites are currently underway to help assess dysbiosis. These will yield a better understanding of the pathophysiology of gastrointestinal diseases and may also lead to new diagnostic and therapeutic approaches to dysbiosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intestinal M cells.

PubMed

Ohno, Hiroshi

2016-02-01

We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer's patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Acute appendicitis with unusual dual pathology.

PubMed

Riddiough, Georgina E; Bhatti, Imran; Ratliff, David A

2012-01-01

Meckel's diverticulum is a rare congenital abnormality arising due to the persistence of the vitelline duct in 1-3% of the population. Clinical presentation is varied and includes rectal bleeding, intestinal obstruction, diverticulitis and ulceration; therefore diagnosis can be difficult. We report a case of acute appendicitis complicated by persistent post operative small bowel obstruction. Further surgical examination of the bowel revealed an non-inflamed, inverted Meckel's diverticulum causing intussusception. Intestinal obstruction in patients with Meckel's diverticulum may be caused by volvulus, intussusception or incarceration of the diverticulum into a hernia. Obstruction secondary to intussusception is relatively uncommon and frequently leads to a confusing and complicated clinical picture. Consideration of Meckel's diverticulum although a rare diagnosis is imperative and this case raises the question "should surgeons routinely examine the bowel for Meckel's diverticulum at laparoscopy?"

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia-reperfusion in humans.

PubMed

Schreuder, Tim H A; Eijsvogels, Thijs M H; Greyling, Arno; Draijer, Richard; Hopman, Maria T E; Thijssen, Dick H J

2014-02-01

Tea consumption is associated with reduced cardiovascular risk. Previous studies found that tea flavonoids work through direct effects on the vasculature, leading to dose-dependent improvements in endothelial function. Cardioprotective effects of regular tea consumption may relate to the prevention of endothelial ischaemia-reperfusion (IR) injury. Therefore, we examined the effect of black tea consumption on endothelial function and the ability of tea to prevent IR injury. In a randomized, crossover study, 20 healthy subjects underwent 7 days of tea consumption (3 cups per day) or abstinence from tea. We examined brachial artery (BA) endothelial function via flow-mediated dilation (FMD), using high resolution echo-Doppler, before and 90 min after tea or hot water consumption. Subsequently, we followed a 20-min ischaemia and 20-min reperfusion protocol of the BA after which we measured FMD to examine the potential of tea consumption to protect against IR injury. Tea consumption resulted in an immediate increase in FMD% (pre-consumption: 5.8 ± 2.5; post-consumption: 7.2 ± 3.2; p < 0.01), whilst no such change occurred after ingestion of hot water. The IR protocol resulted in a significant decrease in FMD (p < 0.005), which was also present after tea consumption (p < 0.001). This decline was accompanied by an increase in the post-IR baseline diameter. In conclusion, these data indicate that tea ingestion improves BA FMD. However, the impact of the IR protocol on FMD was not influenced by tea consumption. Therefore, the cardioprotective association of tea ingestion relates to a direct effect of tea on the endothelium in humans in vivo.

Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS).

PubMed

Heilmann, Romy M; Guard, Melissa M; Steiner, Jörg M; Suchodolski, Jan S; Unterer, Stefan

2017-09-01

Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS. For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α 1 -proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3. These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation. © Veterinary Emergency and Critical Care Society 2017.

New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

PubMed Central

Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

2016-01-01

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

Changes in Intestinal Microbiota Affect Metabolism of Ginsenoside Re.

PubMed

Zhang, Lei; Li, Fei; Qin, Wang-Jun; Fu, Chao; Zhang, Xiang-Lin

2018-05-10

Ginsenoside Re, an active ingredient in Panax ginseng, is widely used as a therapeutic and nutriment. Intestinal microbiota plays crucial roles in modulating the pharmacokinetics and pharmacological actions of ginsenoside Re. The aim of this study was to explore the relationship between bacterial community variety and the metabolic profiles of ginsenoside Re. We developed two models with intestinal dysbacteriosis: a pseudo-germ-free model induced by a non-absorbable antimicrobial mixture (ATM), and Qi-deficiency model established via over-fatigue and acute cold stress (OACS). First, the bacterial community structures in control, ATM, and OACS rats were compared via 16S rRNA amplicon sequencing. Then, gut microbial metabolism of ginsenoside Re was assessed qualitatively and quantitatively in the three groups by UPLC-Q-TOF/MS and HPLC-TQ-MS, respectively. Ten metabolites of ginsenoside Re were detected and tentatively identified, three of which were novel. Moreover, due to significant differences in bacterial communities, deglycosylated products, as the main metabolites of ginsenoside Re, were produced at lower levels in ATM and OACS models. Importantly, the levels of these deglycosylated metabolites correlated with alterations in Prevotella, Lactobacillus, and Bacteroides populations, as well as glycosidase activities. Collectively, biotransformation of ginsenoside Re is potentially influenced by regulating the composition of intestinal microbiota and glycosidase activities. This article is protected by copyright. All rights reserved.

Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins.

PubMed

Pattison, Amanda M; Blomain, Erik S; Merlino, Dante J; Wang, Fang; Crissey, Mary Ann S; Kraft, Crystal L; Rappaport, Jeff A; Snook, Adam E; Lynch, John P; Waldman, Scott A

2016-10-01

Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The intestinal complement system in inflammatory bowel disease: Shaping intestinal barrier function.

PubMed

Sina, Christian; Kemper, Claudia; Derer, Stefanie

2018-06-01

The complement system is part of innate sensor and effector systems such as the Toll-like receptors (TLRs). It recognizes and quickly systemically and/or locally respond to microbial-associated molecular patterns (MAMPs) with a tailored defense reaction. MAMP recognition by intestinal epithelial cells (IECs) and appropriate immune responses are of major importance for the maintenance of intestinal barrier function. Enterocytes highly express various complement components that are suggested to be pivotal for proper IEC function. Appropriate activation of the intestinal complement system seems to play an important role in the resolution of chronic intestinal inflammation, while over-activation and/or dysregulation may worsen intestinal inflammation. Mice deficient for single complement components suffer from enhanced intestinal inflammation mimicking the phenotype of patients with chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD) or ulcerative colitis (UC). However, the mechanisms leading to complement expression in IECs seem to differ markedly between UC and CD patients. Hence, how IECs, intestinal bacteria and epithelial cell expressed complement components interact in the course of IBD still remains to be mostly elucidated to define potential unique patterns contributing to the distinct subtypes of intestinal inflammation observed in CD and UC. Copyright © 2018 Elsevier Ltd. All rights reserved.

The intestine is a blender

NASA Astrophysics Data System (ADS)

Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

The intestine is a blender

NASA Astrophysics Data System (ADS)

Yang, Patricia; Lamarca, Morgan; Hu, David

2015-11-01

According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

Acute mesenteric ischemia after heart surgery.

PubMed

Goleanu, V; Alecu, L; Lazar, O

2014-01-01

Acute mesenteric ischemia (AMI) is a rare but very severe complication of heart surgery, due especially to the delay in setting the correct diagnosis and choosing the appropriate treatment. There are 4 types, but the most frequent is nonocclusive mesenteric ischemia (NOMI). The main mechanism is represented by great decrease or maldistribution of the splenic blood flow, with negative impact on the integrity of the intestinal mucosa, bacterial translocation and multiorganic failure. We present a retrospective study conducted on patients who underwent open heart surgery with cardiopulmonary bypass with non-pulsatile flow. 4 cases of angiographically confirmed NOMI (non-occlusive mesenteric ischemia) were identified. When, based on clinical examination and laboratory findings, acute mesenteric ischemia was suspicioned, superior mesenteric artery angiography was performed via the femoral artery. The main risk factors were represented by: age over 70 years old, left ventricle ejection fraction (LVEF) 35%,aortic clamping time 100 min., chronic kidney failure,counter-pulsation balloon implant, inotropic medication use,like levosimendan, use of blood components 1 unit of erythrocyte mass. Clinical signs were nonspecific. All patients presented hypoventilation, arterial hypotension, oliguria and,from a biological standpoint, metabolic acidosis and leucocytosis. Superior mesenteric artery angiography was the investigation method of choice. Treatment approach was initially medical, followed by resection of the intestine.Mortality was 100%. Acute mesenteric ischemia is a rare but very severe complication in cardiac surgery. It is primordial that the main risk factors be known, and in case of diagnosis suspicion, that it be set as early as possible, along with immediate initiation of an appropriate course of treatment. Celsius.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation

PubMed Central

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-01-01

Background Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. Methods We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Results Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. Conclusions The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes. PMID:28405600

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice*

PubMed Central

Iqbal, Jahangir; Parks, John S.; Hussain, M. Mahmood

2013-01-01

We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92–95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations. PMID:24019513

Disorders of the Small Intestine

MedlinePlus

... Esophagus Disorders of the Stomach Disorders of the Small Intestine Disorders of the Large Intestine Disorders of ... Esophagus Disorders of the Stomach Disorders of the Small Intestine Disorders of the Large Intestine Disorders of ...

[Congenital intestinal lymphangiectasia].

PubMed

Popović, Dugan D j; Spuran, Milan; Alempijević, Tamara; Krstić, Miodrag; Djuranović, Srdjan; Kovacević, Nada; Damnjanović, Svetozar; Micev, Marjan

2011-03-01

Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and supportive therapy. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect.

PubMed

Brencher, Lisa; Verhaegh, Rabea; Kirsch, Michael

2017-05-01

Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular studies of fecal anaerobic commensal bacteria in acute diarrhea in children.

PubMed

Balamurugan, Ramadass; Janardhan, Harish P; George, Sarah; Raghava, M Venkata; Muliyil, Jayaprakash; Ramakrishna, Balakrishnan S

2008-05-01

The commensal bacterial flora of the colon may undergo changes during diarrhea, owing to colonization of the intestine by pathogens and to rapid intestinal transit. This study used molecular methods to determine changes in the composition of selected commensal anaerobic bacteria during and after acute diarrhea in children. Fecal samples were obtained from 46 children with acute diarrhea in a rural community during an episode of acute diarrhea, immediately after recovery from diarrhea, and 3 months after recovery. DNA was extracted and quantitative polymerase chain reaction using SYBR green and genus- and species-specific primers targeting 16S rDNA were undertaken to quantitate the following groups of bacteria: Bifidobacterium spp., Bifidobacterium longum group, Bacteroides-Prevotella group, Bacteroides fragilis, Lactobacillus acidophilus group, Faecalibacterium prauznitzii, and Eubacterium rectale, relative to amplification of universal bacterial domain 16S rDNA. Bacteria belonging to the Bacteroides-Prevotella-Porphyromonas group, E rectale, L acidophilus, and F prauznitzii groups were low during acute diarrhea compared with their levels after recovery from diarrhea. The pattern was similar in rotavirus diarrhea and nonrotavirus diarrhea. Administration of amylase-resistant maize starch as adjuvant therapy was associated with lower levels of F prauznitzii at the time of recovery but did not lead to other changes in the floral pattern. Specific classes of fecal bacteria are lower during episodes of acute diarrhea in children than during periods of normal gastrointestinal health, suggesting specific alterations in the flora during diarrhea.

Intestinal nerves and ion transport: stimuli, reflexes, and responses.

PubMed

Hubel, K A

1985-03-01

The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Eiichi; Hosokawa, Masaya; Faculty of Human Sciences, Tezukayama Gakuin University, Osaka

2011-01-07

Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucosemore » absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a

Pathophysiology of avian intestinal ion transport.

PubMed

Nighot, Meghali; Nighot, Prashant

2018-06-01

The gut has great importance for the commercial success of poultry production. Numerous ion transporters, exchangers, and channels are present on both the apical and the basolateral membrane of intestinal epithelial cells, and their differential expression along the crypt-villus axis within the various intestinal segments ensures efficient intestinal absorption and effective barrier function. Recent studies have shown that intensive production systems, microbial exposure, and nutritional management significantly affect intestinal physiology and intestinal ion transport. Dysregulation of normal intestinal ion transport is manifested as diarrhoea, malabsorption, and intestinal inflammation resulting into poor production efficiency. This review discusses the basic mechanisms involved in avian intestinal ion transport and the impact of development during growth, nutritional and environmental alterations, and intestinal microbial infections on it. The effect of intestinal microbial infections on avian intestinal ion transport depends on factors such as host immunity, pathogen virulence, and the mucosal organisation of the particular intestinal segment.

NMR-based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients.

PubMed

Kumar, Dinesh; Pandey, Gaurav; Bansal, Deepak; Rawat, Atul; Kumar, Umesh; Dubey, Durgesh; Guleria, Anupam; Saraswat, Vivek Anand

2017-04-01

The article presents a simplified NMR-based protocol for urinary profiling of lactulose/mannitol ratio (LMR) and demonstrates here its utility to assess increased intestinal permeability (IP) in patients with acute on chronic liver failure (ACLF). ACLF is a serious clinical complication associated with chronic liver disease (cirrhosis). The major risk factor in its development is increased IP ('leaky gut'), which has been linked to disease progression and to infectious complications. However, IP has seldom been investigated in patients with ACLF, even though patients frequently report gastrointestinal disorders and associated complications. To this end, we first optimized the NMR-based targeted profiling of urinary metabolites (i.e. actulose, mannitol, and creatinine) and subsequently used this resulted protocol (a) first to evaluate the altered IP in ACLF patients and then (b) to explore its utility for monitoring the treatment response in these patients. The normal profiles were obtained for 7 age and sex matched healthy volunteers. The results revealed that the urinary LMR excretion was significantly higher in ACLF patients compared to normal controls (median ~0.7, range (0.12-2.84), vs median ~0.11, range (0.02-0.28), p < 0.001) suggesting that the ACLF patients' exhibit altered IP. However, the LMR excretion in six clinically improved follow-up ACLF patients was comparable to normal controls indicating restored IP after the treatment. The protocol-as demonstrated here with ACLF-is equally applicable for evaluating IP or mucosal barrier function in other intestinal disorders with reasonable sensitivity and specificity, highlighting its general utility. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Intestinal Parasitoses.

ERIC Educational Resources Information Center

Lagardere, Bernard; Dumburgier, Elisabeth

1994-01-01

Intestinal parasites have become a serious public health problem in tropical countries because of the climate and the difficulty of achieving efficient hygiene. The objectives of this journal issue are to increase awareness of the individual and collective repercussions of intestinal parasites, describe the current conditions of contamination and…

Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina.

PubMed

Michalski, D; Härtig, W; Krügel, K; Edwards, R H; Böddener, M; Böhme, L; Pannicke, T; Reichenbach, A; Grosche, A

2013-02-12

There is accumulating evidence that glutamate and GABA release are key mechanisms of ischaemic events in the CNS. However, data on the expression of involved transporters for these mediators are inconsistent, potentially impeding further neuroprotective approaches. Here, we applied immunofluorescence labelling to characterise the expression pattern of vesicular glutamate (VGLUT) and GABA transporters (VGAT) after acute focal cerebral ischaemia and in two models of retinal ischaemia. Mice were subjected to filament-based focal cerebral ischaemia predominantly involving the middle cerebral artery territory, also leading to retinal ischaemia due to central retinal artery occlusion (CRAO). Alternatively, retinal ischaemia was induced by a transient increase of the intraocular pressure (HIOP). One day after ischaemia onset, diminished immunolabelling of neuronal nuclei and microtubule-associated protein 2-positive structures were found in the ipsilateral neocortex, subcortex and the retina, indicating neuronal degeneration. VGLUT1 expression did not change significantly in ischaemic tissues whereas VGLUT2 was down-regulated in specific areas of the brain. VGLUT3 expression was only slightly down-regulated in the ischaemia-affected neocortex, and was found to form clusters on fibrils of unknown origin in the ischaemic lateral hypothalamus. In contrast, retinae subjected to CRAO or HIOP displayed a rapid loss of VGLUT3-immunoreactivity. The expression of VGAT appears resistant to ischaemia as there was no significant alteration in all the regions analysed. In summary, these data indicate a region- and subtype-specific change of VGLUT expression in the ischaemia-affected CNS, whose consideration might help to generate specific neuroprotective strategies. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

PubMed Central

Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, M. Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2011-01-01

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria–derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40’s effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation. PMID:21606592

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

PubMed Central

Azzam, Edouard I.; Ferraris, Ronaldo P.; Howell, Roger W.

2015-01-01

We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays. PMID:26484399

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation.

PubMed

Roche, Marjolaine; Neti, Prasad V S V; Kemp, Francis W; Azzam, Edouard I; Ferraris, Ronaldo P; Howell, Roger W

2015-11-01

We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays.

Lactobacillus acidophilus attenuates Salmonella-induced intestinal inflammation via TGF-β signaling.

PubMed

Huang, I-Fei; Lin, I-Chun; Liu, Pei-Feng; Cheng, Ming-Fang; Liu, Yen-Chen; Hsieh, Yao-Dung; Chen, Jih-Jung; Chen, Chun-Lin; Chang, Hsueh-Wei; Shu, Chih-Wen

2015-10-07

Salmonella is a common intestinal pathogen that causes acute and chronic inflammatory response. Probiotics reduce inflammatory cytokine production and serve as beneficial commensal microorganisms in the human gastrointestinal tract. TGF-β (transforming growth factor β)/SMAD and NF-κB signaling play important roles in inflammation in intestinal cells. However, the involvement of the signaling in regulating inflammation between Salmonella and probiotics is not fully understood. L. acidophilus and prebiotic inulin were used to treat human intestinal Caco-2 cells prior to infection with Salmonella. The cells were harvested to examine the cytokines and MIR21 expression with immunoblotting and real-time PCR. NF-κB and SMAD3/4 reporter vectors were transfected into cells to monitor inflammation and TGF-β1 signaling, respectively. In this study, we showed that the probiotic L. acidophilus decreased Salmonella-induced NF-κB activation in human intestinal Caco-2 cells. Expression of the inflammatory cytokines, TNF-α and IL-8, in L. acidophilus-pretreated cells was also significantly lower than that in cells infected with Salmonella alone. Moreover, TGF-β1 and MIR21 expression was elevated in cells pretreated with L. acidophilus or synbiotic, a combination of inulin and L. acidophilus, compared to that in untreated cells or cells infected with S. typhimurium alone. By contrast, expression of SMAD7, a target of MIR21, was accordingly reduced in cells treated with L. acidophilus or synbiotics. Consistent with TGF-β1/MIR21 and SMAD7 expression, SMAD3/4 transcriptional activity was significantly higher in the cells treated with L. acidophilus or synbiotics. Furthermore, TGF-β1 antibody antagonized the SMAD3/4 and NF-κB transcriptional activity modulated by L. acidophilus in intestinal cells. Our results suggest that the TGF-β1/MIR21 signaling pathway may be involved in the suppressive effects of L. acidophilus on inflammation caused by S. typhimurium in intestinal

Intestinal development and differentiation

PubMed Central

Noah, Taeko K.; Donahue, Bridgitte; Shroyer, Noah F.

2011-01-01

In this review, we present an overview of intestinal development and cellular differentiation of the intestinal epithelium. The review is separated into two sections: Section one summarizes organogenesis of the small and large intestines, including endoderm and gut tube formation in early embryogenesis, villus morphogenesis, and crypt formation. Section two reviews cell fate specification and differentiation of each cell type within the intestinal epithelium. Growth factor and transcriptional networks that regulate these developmental processes are summarized. PMID:21978911

Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.

PubMed

Slottosch, Ingo; Liakopoulos, Oliver; Kuhn, Elmar; Deppe, Antje; Lopez-Pastorini, Alberto; Schwarz, David; Neef, Klaus; Choi, Yeong-Hoon; Sterner-Kock, Anja; Jung, Kristina; Mühlfeld, Christian; Wahlers, Thorsten

2014-12-01

Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. © The Author 2014. Published by Oxford University Press on behalf of

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

PubMed

Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

2016-01-01

In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Intestinal alkaline phosphatase is protective to the preterm rat pup intestine.

PubMed

Heinzerling, Nathan P; Liedel, Jennifer L; Welak, Scott R; Fredrich, Katherine; Biesterveld, Ben E; Pritchard, Kirkwood A; Gourlay, David M

2014-06-01

Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown that enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNFα, IL-6 and iNOS and permeability and cytokine expression after LPS exposure. There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal Alkaline Phosphatase Is Protective to the Preterm Rat Pup Intestine

PubMed Central

Heinzerling, Nathan P.; Liedel, Jennifer L.; Welak, Scott R.; Fredrich, Katherine; Biesterveld, Ben E.; Pritchard, Kirkwood A.; Gourlay, David M.

2014-01-01

Background Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Methods Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNF-a, IL-6 and iNOS and permeability and cytokine expression after LPS. exposure. Results There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Conclusions Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. PMID:24888842

The relationship between intestinal parasites and some immune-mediated intestinal conditions

PubMed Central

Mohammadi, Rasoul; Hosseini-Safa, Ahmad; Ehsani Ardakani, Mohammad Javad; Rostami-Nejad, Mohammad

2015-01-01

Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestine and characterized by a multitude gastrointestinal (GI) and extra GI symptoms. IBD (including ulcerative colitis and Crohn’s disease) is a group of inflammatory conditions of the small intestine and colon. The etiology of IBD is unknown, but it may be related to instability in the intestinal microflora that leading to an immoderate inflammatory response to commensal microbiota. Irritable bowel syndrome (IBS) is a common, long-term condition of the digestive system. Bloating, diarrhoea and/or constipation are nonspecific symptoms of IBS. Various studies have shown that some intestinal parasites can effect on immune system of infected hosts and in some cases, they are able to modify and change the host’s immune responses, particularly in autoimmune disorders like celiac disease and IBD. The main objective of this review is to investigate the relationship between intestinal parasites and different inflammatory bowel disorders. PMID:25926937

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

PubMed Central

Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.

2018-01-01

The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. PMID:29593681

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biophysical models, which describe the dynamics of vital body systems (namely, hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation, are developed. These models, based on conventional biological theories, are realized as the systems of nonlinear differential equations. Their variables and constant parameters have real biological meaning, that provides successful identification and verification of the models in hand. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. It is proved that the predictions the models agree with the respective experimental data at both qualitative and quantitative levels. All this testifies to the efficiency of employment of the developed models in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems, that can be used for the radiation risk assessment in the long-term space missions such as lunar colony and Mars voyage.

Clinics in diagnostic imaging (171). Caecal volvulus with underlying intestinal malrotation.

PubMed

Ooi, Su Kai Gideon; Tan, Tien Jin; Ngu, James Chi Yong

2016-11-01

A 46-year-old Chinese woman with a history of cholecystectomy and appendicectomy presented to the emergency department with symptoms of intestinal obstruction. Physical examination revealed central abdominal tenderness but no clinical features of peritonism. Plain radiography of the abdomen revealed a grossly distended large bowel loop with the long axis extending from the right lower abdomen toward the epigastrium, and an intraluminal air-fluid level. These findings were suspicious for an acute caecal volvulus, which was confirmed on subsequent contrast-enhanced computed tomography (CT) of the abdomen and pelvis. CT demonstrated an abnormal positional relationship between the superior mesenteric vein and artery, indicative of an underlying intestinal malrotation. This case highlights the utility of preoperative imaging in establishing the diagnosis of an uncommon cause of bowel obstruction. It also shows the importance of recognising the characteristic imaging features early, so as to ensure appropriate and expedient management, thus reducing patient morbidity arising from complications. Copyright: © Singapore Medical Association.

Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

PubMed

Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick

2016-11-01

The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P < .05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P < .01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P < .01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P < .01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Acute intestinal obstruction caused by a persimmon phytobezoar after dissolution therapy with Coca-Cola.

PubMed

Ha, Seung Soo; Lee, Hyun Suk; Jung, Min Kyu; Jeon, Seong Woo; Cho, Chang Min; Kim, Sung Kook; Choi, Yong Hwan

2007-12-01

Bezoars are concretions or hard masses of foreign matter that are found in the gastrointestinal tract. Recent reports have demonstrated the efficacy of Coca-Cola administration for the dissolution of phytobezors. Here we report on a 73-year-old man with a very large gastric persimmon diospyrobezoar, and this caused small intestinal obstruction after partial dissolution with oral and injected Coca-Cola.

Apple-peel intestinal atresia: enteroplasty for intestinal lengthening and primary anastomosis.

PubMed

Onofre, Luciano Silveira; Maranhão, Renato Frota de Albuquerque; Martins, Elaine Cristina Soares; Fachin, Camila Girardi; Martins, Jose Luiz

2013-06-01

Apple-peel atresia (or Type-IIIb intestinal atresia) is an unusual type of jejunoileal atresia. They present with jejunal atresia near the ligament of Treitz and a foreshortened small bowel. Many surgical options have been used, but the optimal method of repair remains unclear. We present a case of a newborn with apple-peel intestinal atresia managed by enteroplasty for intestinal lengthening and primary anastomosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Limb salvage following iatrogenic arterial injury: complications of cardiac support using intra-aortic balloon pumps.

PubMed

Hunt, Adam; Waldin, Owen; Slim, Hani; Brar, Ranjeet

2016-06-06

This is a unique case report describing complex limb salvage in a patient who experienced acute limb ischaemia due to a complication of intra-aortic balloon pump (IABP) counterpulsation. This case focuses on a patient who had an IABP counterpulsation device inserted following myocardial infarction, requiring urgent coronary artery bypass grafting for acute coronary syndrome. Postoperatively, the IABP could not be removed, with consequent iliac thrombosis and acute limb ischaemia. Emergency femoral-to-femoral crossover bypass was performed using a polytetrafluoroethylene graft. A portion of the IABP balloon tip was entrapped and retained, however, and became the focus of delayed septicaemia, resulting in graft infection and wound breakdown 6 weeks later. Explantation of the residual balloon tip, ligation of the right external iliac artery and redo femoral-femoral crossover using the great saphenous vein were successfully performed. 2016 BMJ Publishing Group Ltd.

Electrical stimulation-based renal nerve mapping exacerbates ventricular arrhythmias during acute myocardial ischaemia.

PubMed

Huang, Bing; Zhou, Xiaoya; Wang, Menglong; Li, Xuefei; Zhou, Liping; Meng, Guannan; Wang, Yuhong; Wang, Zhuo; Wang, Songyun; Yu, Lilei; Jiang, Hong

2018-06-01

Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.

Convergence of External Crohn’s Disease Risk Factors on Intestinal Bacteria

PubMed Central

Oberc, Alexander; Coombes, Brian K.

2015-01-01

Crohn’s disease (CD) is an immune-mediated intestinal illness that significantly compromises health in many developed countries. Although definitive causes remain elusive, the required contribution of microbes in the progression of disease has become an accepted concept. Known CD risk factors, such as antibiotic use and acute infectious gastroenteritis, may impact the gut. This concept is now being explored with a view toward understanding the beneficial and unfavorable microbes that may be altered in numbers during such external insults. A comprehensive understanding of the microbial component to CD could be useful clinically as future therapies may focus on preventing risk exposures on susceptible individuals, eliminating harmful microbes, or restoring a protective gut microbiome. Here, we examine how acute infectious gastroenteritis and antibiotic exposure may impact the gut microbiota in the context of inflammation in CD. PMID:26579131

Intestinal pseudo-obstruction

MedlinePlus

... Staying in bed for long periods of time (bedridden). Taking drugs that slow intestinal movements. These include ... be tried: Colonoscopy may be used to remove air from the large intestine. Fluids can be given ...

Severe delayed complication after percutaneous endoscopic colostomy for chronic intestinal pseudo-obstruction: A case report and review of the literature

PubMed Central

Bertolini, David; De Saussure, Philippe; Chilcott, Michael; Girardin, Marc; Dumonceau, Jean-Marc

2007-01-01

Percutaneous endoscopic colostomy (PEC) is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient’s quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications. PMID:17465514

Severe delayed complication after percutaneous endoscopic colostomy for chronic intestinal pseudo-obstruction: a case report and review of the literature.

PubMed

Bertolini, David; De Saussure, Philippe; Chilcott, Michael; Girardin, Marc; Dumonceau, Jean-Marc

2007-04-21

Percutaneous endoscopic colostomy (PEC) is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient's quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications.

The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases

PubMed Central

Kim, Min-Hyun; Kim, Hyeyoung

2017-01-01

Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. PMID:28498331

Acute Intestinal Obstruction Caused by a Persimmon Phytobezoar after Dissolution Therapy with Coca-Cola

PubMed Central

Ha, Seung Soo; Lee, Hyun Suk; Jung, Min Kyu; Cho, Chang Min; Kim, Sung Kook; Choi, Yong Hwan

2007-01-01

Bezoars are concretions or hard masses of foreign matter that are found in the gastrointestinal tract. Recent reports have demonstrated the efficacy of Coca-Cola administration for the dissolution of phytobezors. Here we report on a 73-year-old man with a very large gastric persimmon diospyrobezoar, and this caused small intestinal obstruction after partial dissolution with oral and injected Coca-Cola. PMID:18309693

Small Intestine Disorders

MedlinePlus

Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the ...

Acute appendicitis with unusual dual pathology

PubMed Central

Riddiough, Georgina E.; Bhatti, Imran; Ratliff, David A.

2011-01-01

INTRODUCTION Meckel's diverticulum is a rare congenital abnormality arising due to the persistence of the vitelline duct in 1–3% of the population. Clinical presentation is varied and includes rectal bleeding, intestinal obstruction, diverticulitis and ulceration; therefore diagnosis can be difficult. PRESENTATION OF CASE We report a case of acute appendicitis complicated by persistent post operative small bowel obstruction. Further surgical examination of the bowel revealed an non-inflamed, inverted Meckel's diverticulum causing intussusception. DISCUSSION Intestinal obstruction in patients with Meckel's diverticulum may be caused by volvulus, intussusception or incarceration of the diverticulum into a hernia. Obstruction secondary to intussusception is relatively uncommon and frequently leads to a confusing and complicated clinical picture. CONCLUSION Consideration of Meckel's diverticulum although a rare diagnosis is imperative and this case raises the question “should surgeons routinely examine the bowel for Meckel's diverticulum at laparoscopy?” PMID:22288035

Normothermic extracorporeal perfusion of isolated porcine liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Suzuki, Satoshi; Marino, Bruno; Starkey, Graeme K; Chambers, Brenton; Fink, Michael A; Wang, Bao Zhong; Houston, Shane; Eastwood, Glenn; Calzavacca, Paolo; Glassford, Neil; Skene, Alison; Jones, Daryl A; Jones, Robert

2012-09-01

Liver transplantation is a major life-saving procedure, and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers. We conducted proof-of-concept experiments using a DCD model in the pig to assess the short-term (4 hours) feasibility and functional efficacy of NELP. Using extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion, and physiological perfusion pressures, we achieved NELP and evidence of function (bile production, paracetamol removal, maintenance of normal ammonia and lactate levels) for 4 hours in pig livers subjected to 15 and 30 minutes of cardiac arrest before explantation. Our experiments justify further investigations of the feasibility and efficacy of human DCD liver preservation by ex-vivo perfusion.

The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension.

PubMed

Price, Laura C; Dimopoulos, Konstantinos; Marino, Philip; Alonso-Gonzalez, Rafael; McCabe, Colm; Kemnpy, Aleksander; Swan, Lorna; Boutsikou, Maria; Al Zahrani, Ahmed; Coghlan, Gerry J; Schreiber, Benjamin E; Howard, Luke S; Davies, Rachel; Toshner, Mark; Pepke-Zaba, Joanna; Church, Alistair C; Peacock, Andrew; Corris, Paul A; Lordan, James L; Gaine, Sean; Condliffe, Robin; Kiely, David G; Wort, Stephen John

2017-11-01

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expression of an intestine-specific transcription factor (CDX1) in intestinal metaplasia and in subsequently developed intestinal type of cholangiocarcinoma in rat liver.

PubMed

Ren, P; Silberg, D G; Sirica, A E

2000-02-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478-486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats.

Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine

PubMed Central

Hoekstra, Nadia; Collins, Danielle; Collaco, Anne; Baird, Alan W.; Winter, Desmond C.; Ameen, Nadia; Geibel, John P.; Kopic, Sascha

2013-01-01

Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR), is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK), can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX) mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK). In order to substantiate our findings on the whole tissue level, short-circuit current (SCC) was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK) significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness. PMID:23935921

TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism

PubMed Central

Ha, Tuanzhu; Hu, Yulong; Liu, Li; Lu, Chen; McMullen, Julie R.; Kelley, Jim; Kao, Race L.; Williams, David L.; Gao, Xiang; Li, Chuanfu

2010-01-01

Aims Toll-like receptor (TLR)-mediated signalling pathways have been implicated in myocardial ischaemia/reperfusion (I/R) injury. Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway protects the myocardium from ischaemic injury. We hypothesized that the modulation of TLR2 would induce cardioprotection against I/R injury via activation of the PI3K/Akt signalling. Methods and results Mice were treated with TLR2 ligands, peptidoglycan (PGN) or Pam3CSK4, respectively, 1 h before the hearts were subjected to ischaemia (1 h), followed by reperfusion (4 h). Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac function and haemodynamic performance were evaluated. Infarct size was significantly reduced in PGN- or Pam3CSK4-treated mice compared with untreated I/R mice. Administration of TLR2 ligands improved cardiac function following I/R. PGN treatment increased the levels of phospho-Akt and phospho-GSK-3β (glycogen synthase kinase-3β), compared with untreated I/R hearts. PGN stimulation increased TLR2 tyrosine phosphorylation and association of the p85 subunit of PI3K with TLR2. To investigate the role of PI3K/Akt signalling in PGN-induced cardioprotection, we administered the PI3K inhibitor, Wortmannin, to the mice 15 min before PGN treatment. We also administered PGN to kinase-deficient Akt (kdAkt) transgenic mice 1 h before myocardial I/R. Both PI3K inhibition and kdAkt mice abolished the cardioprotection induced by PGN. To examine the role of TLR2 in PGN-induced cardioprotection, we administrated PGN to TLR2 knockout mice 1 h before the hearts were subjected to I/R. PGN-induced cardioprotection was lost in TLR2-deficient mice. Conclusion These results demonstrate that TLR2 ligands induced cardioprotection, which is mediated through a TLR2/PI3K/Akt-dependent mechanism. PMID:20421349

Characterization of the endocrine, digestive and morphological adjustments of the intestine in response to food deprivation and torpor in cunner, Tautogolabrus adspersus.