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Sample records for acute intestinal ischaemia

  1. Mast cells drive mesenteric afferent signalling during acute intestinal ischaemia

    PubMed Central

    Jiang, Wen; Kirkup, Anthony J; Grundy, David

    2011-01-01

    Abstract Acute intestinal ischaemia stimulates visceral afferent nerves but the mechanisms responsible for this excitation are not fully understood. Mast cells may participate in this process as they are known to signal to mesenteric afferents during intestinal anaphylaxis and contribute to early inflammation and neuronal damage in response to cerebral ischaemia. We therefore hypothesised that mast cells are early responders to acute intestinal ischaemia and their activation initiates rapid signalling to the CNS via the excitation of mesenteric afferents. Primary afferent firing was recorded from a mesenteric nerve bundle supplying a segment of jejunum in anaesthetized adult rats. Acute focal ischaemia was produced by clamping the mesenteric vessels for 8 min, and reperfusion followed removal of the vessel clip. Two episodes of ischaemia–reperfusion (I–R) separated by a 30 min interval were performed. Drugs or their vehicles were administered 10 min before the 2nd I–R episode. Ischaemia caused a reproducible, intense and biphasic afferent firing that was temporally dissociated from the concomitantly triggered complex pattern of intestinal motor activity. The L-type calcium channel blocker, nifedipine, significantly attenuated this afferent firing by a mechanism independent of its action on intestinal tone. Ischaemia-induced afferent firing was also abrogated by the mast cell stabilizer, doxantrazole, and the H1 histamine receptor antagonist, pyrilamine. In contrast, the nicotinic receptor antagonist, hexamethonium, and the N-type calcium channel toxin, ω-conotoxin GVIA, each reduced the ischaemia-evoked motor inhibition but not the concurrent afferent discharge. Similarly, the cyclooxygenase inhibitor, naproxen, had no effect on the ischaemic afferent response but reduced the intestinal tone shortly from the onset of ischaemia to the early period of reperfusion. These data support a critical role for mast cell-derived histamine in the direct chemoexcitation

  2. VSL#3 probiotics provide protection against acute intestinal ischaemia/reperfusion injury.

    PubMed

    Salim, S Y; Young, P Y; Lukowski, C M; Madsen, K L; Sis, B; Churchill, T A; Khadaroo, R G

    2013-12-01

    Acute intestinal ischaemia/reperfusion injury (AII/R) is an adaptive physiologic response during critical illness, involving mesenteric vasoconstriction and hypoperfusion. Prevention of AII/R in high risk patient populations would have a significant impact on morbidity and mortality. The purpose of this study was to investigate the protective effects of VSL#3 probiotic treatment in a murine model of AII/R. Adult 129/SvEv mice were subjected to an experimental AII/R model using superior mesenteric artery occlusion. Animals were pre-treated with either three days or two weeks of VSL#3 probiotics. Local tissue injury markers were assessed by levels of myeloperoxidase and activation of nuclear factor kappa B (NFкB). Systemic and local cytokines, including interleukin (IL)-1β, IL- 10, TNFα, and interferon gamma were measured by ELISA and multiplex fluorescent detection. VSL#3 probiotics reduced local tissue inflammation and injury due to AII/R. A two-week course of VSL#3 was more effective than a shorter three-day course. The reduction in local inflammation from the two-week course of VSL#3 is correlated to a significant reduction in levels of active IL-1β, and tissue levels of myeloperoxidase. Levels of active NFкB were significantly elevated in the vehicle-fed AII/R mice, corroborating with tissue inflammation, which were attenuated by VSL#3 administrations. VSL#3 did not cause any systemic inflammation or lung injury. VSL#3 probiotics are effective in reducing local tissue injury from AII/R by down-regulating pro-inflammatory mediators and immune cell recruitment. This study highlights a potential role for VSL#3 in management of patients at high risk for AII/R.

  3. Acute mesenteric ischaemia and unexpected death.

    PubMed

    Byard, Roger W

    2012-05-01

    Acute mesenteric ischaemia is a vascular emergency that arises when blood flow to the intestine is compromised leading to tissue necrosis. It is primarily a condition of the elderly associated with significant morbidity and mortality. Causes include arterial thromboembolism, venous thrombosis and splanchnic vasoconstriction (so-called nonocclusive mesenteric ischaemia). Reperfusion injury and breakdown of the intestinal mucosal barrier lead to metabolic derangements, sepsis and death from multiorgan failure. The diagnosis may be difficult to make clinically and numbers of cases are increasing due to ageing of the population. The clinical and pathological features are reviewed with discussion of predisposing conditions. Careful dissection of the mesenteric vasculature is required at autopsy with appropriate histologic sampling and documentation of associated comorbidities. Other organs need to be checked for thrombi and the possibility of testing for inherited thombophilias should be considered. Toxicological evaluation, particularly in younger individuals, may reveal evidence of cocaine use. On occasion no obstructive lesions will be demonstrated, however the confounding effects of post-mortem autolytic and putrefactive changes may mean that nonocclusive mesenteric ischaemia may be difficult to diagnose.

  4. Electrophysiological measures of acute cerebral ischaemia

    NASA Astrophysics Data System (ADS)

    Ferree, T. C.; Hwa, R. C.

    2005-09-01

    A method of EEG analysis is described which provides new insights into EEG pathology in cerebral ischaemia. The method is based on a variant of detrended fluctuation analysis (DFA), which reduces short (10 s) segments of spontaneous EEG time series to two dimensionless scaling exponents. The spatial variability of each exponent is expressed in terms of its statistical moments across EEG channels. Linear discriminant analysis combines the moments into concise indices, which distinguish normal and stroke groups remarkably well. On average over the scalp, stroke patients have larger fluctuations on the longest time scales. This is consistent with the notion of EEG slowing, but extends that notion to a wider range of time scales. The higher moments show that stroke patients have markedly reduced variability over the scalp. This contradicts the notion of a purely focal EEG scalp topography and argues instead for a highly distributed effect. In these indices, subacute patients appear further from normal than acute patients.

  5. Chronic intestinal ischaemia: measurement of the total splanchnic blood flow.

    PubMed

    Zacho, Helle D

    2013-04-01

    A redundant collateral network between the intestinal arteries is present at all times. In case of ischaemia in the gastrointestinal tract, the collateral blood supply can develop further, thus accommodating the demand for oxygen even in the presence of significant stenosis or occlusion of the intestinal arteries without clinical symptoms of intestinal ischaemia. Symptoms of ischemia develop when the genuine and collateral blood supply no longer can accommodate the need for oxygen. Atherosclerosis is the most common cause of obliteration in the intestinal arteries. In chronic intestinal ischaemia (CII), the fasting splanchnic blood flow (SBF) is sufficient, but the postprandial increase in SBF is inadequate and abdominal pain will therefore develop in relation to food intake causing the patient to eat smaller meals at larger intervals with a resulting weight loss. Traditionally, the CII-diagnosis has exclusively been based upon morphology (angiography) of the intestinal arteries; however, substantial discrepancies between CII-symptoms and the presence of atherosclerosis/stenosis in the intestinal arteries have been described repeatedly in the literature impeding the diagnosis of CII. This PhD thesis explores a method to determine the total SBF and its potential use as a diagnostic tool in patients suspected to suffer from CII. The SBF can be measured using a continuous infusion of a tracer and catheterisation of a hepatic vein and an artery. By measuring the SBF before and after a standard meal it is possible to assess the ability or inability to enhance the SBF and thereby diagnosing CII. In Study I, measurement of SBF was tested against angiography in a group of patients suspected to suffer from CII due to pain and weight loss. A very good agreement between the postprandial increase in SBF and angiography was found. The method was validated against a well-established method independent of the hepatic extraction of tracer using pAH in a porcine model (study II

  6. Source of net water and electrolyte loss following intestinal ischaemia.

    PubMed

    Robinson, J W; Winistörfer, B; Mirkovitch, V

    1980-01-01

    Ischaemia of the dog intestine lasting 1 h causes desquamation of the epithelium at the villus tips and congestion in the villus capillaries. The crypt cells are relatively undamaged. These changes are associated with a loss of active transport of organic solutes, determined in vitro, a reduction in mucosal sucrase activity and an abolition of glucose absorption in vivo. A profuse net loss of water and electrolytes into the lumen in vivo develops. The net sodium loss is due primarily to an inhibition of the lumen-blood flux of this ion, the blood-lumen flux being relatively unchanged. In uraemic dogs, the loss of urea into the lumen is the same in control and ischaemic loops, testifying to the lack of change in the unidirectional water flow from blood to lumen. Perfusion of the dog intestine with 1% Triton X-100 leads to morphological changes that have certain similarities with those provoked by ischaemia. Damage was restricted to the villus tips, protection from further alterations apparently being provided by a mucus layer that forms on the mucosal surface; the crypt region remained unchanged. After 10 min exposure, organic solute transport in vitro and glucose absorption in vivo were both reduced by not abolished; sodium and water absorption in vivo were suppressed, but no net secretion occurred. To account for these observations, we have suggested that the normal crypt cell is a secretory element with respect to sodium and water. During maturation, its absorptive properties develop such that the mature enterocyte, possessing both absorptive and secretory mechanisms, is capable of net absorption of sodium. After destruction of the villus tips, net secretion continues in the crypts; if there are insufficient villus cells remaining to ensure reabsorption, a net secretory capacity is observed.

  7. Transmural triglycerides in acute myocardial ischaemia.

    PubMed

    Jesmok, G J; Warltier, D C; Gross, G J; Hardman, H F

    1978-11-01

    The effect of coronary artery occlusion on endogenous triglycerides of left ventricular subepicardium and subendocardium was studied in the open-chest anaesthetised dog. Under control conditions, the subepicardium was found to have a greater concentration of triglycerides than the subendocardium. Thirty minutes after acute coronary artery occlusion there was a decrease followed by a steady increase at 60, 120, and 240 min in subepicardial triglycerides of the ischaemic region. No change in triglycerides in the subendocardium of normal or ischaemic regions was observed. The initial decrease of subepicardial triglycerides in the ischaemic region was blocked by administration of propranolol or bevantolol (CI-775; a specific beta 1 antagonist) given 30 min before occlusion. It is concluded that the effect of coronary artery ligation on transmural endogenous triglycerides is biphasic with an initial period of increased mobilisation followed by a period of increased deposition.

  8. Cortical venous infarcts and acute limb ischaemia in acute carbon monoxide poisoning: A rare case report.

    PubMed

    Hanif, Muhammad Farooq; Iqbal, Beenish; Gilani, Nooman

    2016-06-01

    A case of carbon monoxide poisoning is presented with unusual complications; some of which have not been reported previously. A 48-years-old Asian male presented to the emergency department with dyspnoea, altered state of consciousness and pale discolouration of skin after being locked inside a factory room with burning coal. Patient was in acute respiratory distress. Arterial blood gas analysis showed respiratory acidosis with hypoxaemia. On 3rd day, patient developed dark coloured urine and right upper limb ischaemia. Acute renal failure was diagnosed. A doppler ultrasound showed stenosis of radial and ulnar arteries. 0n 8th day, patient regained consciousness and complained of loss of vision. An MRI of the brain revealed bilateral occipital venous infarcts. Cortical venous infarcts and arterial stenosis are rare complications of acute carbon monoxide poisoning.

  9. TGF-β1 improves mucosal IgA dysfunction and dysbiosis following intestinal ischaemia-reperfusion in mice.

    PubMed

    Zhang, Xu-Yu; Liu, Zi-Meng; Zhang, Hu-Fei; Li, Yun-Sheng; Wen, Shi-Hong; Shen, Jian-Tong; Huang, Wen-Qi; Liu, Ke-Xuan

    2016-06-01

    Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF)-β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF-β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF-β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF-β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria-binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor-β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF-β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB-431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF-β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF-β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF-β receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF-β1.

  10. Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets.

    PubMed

    Leifert, J A; Bossaller, L; Uhl, M

    2008-11-01

    Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.

  11. Acute colonic ischaemia in rats results in long-term structural changes without alterations of colonic sensitivity

    PubMed Central

    Ravnefjord, Anna; Pettersson, Madeleine; Rehnström, Erika; Martinez, Vicente

    2008-01-01

    Colonic ischaemia and mast cells have been involved in the pathophysiology of the functional gastrointestinal disorder irritable bowel syndrome, although the cause–effect relationships remain unknown. We assessed long-term histopathological and functional changes associated to an acute ischaemic episode (1 h) of the colon, followed by 8-week recovery, in rats. Functional colonic alterations [sensitivity during colorectal distension (CRD), compliance and propulsive motility] were assessed regularly during the recovery. Colonic histopathology (presence of inflammation, morphometric alterations and variations in neuronal density in the enteric nervous system) 8-week postischaemia was assessed. Following ischaemia, none of the functional parameters tested (motility, sensitivity and compliance) were affected. At necropsy, the colon presented an overall normal appearance with an increase in weight of the ischaemic area (mg/cm: 99 ± 6; P < 0.05 vs. control: 81 ± 4 or sham ischaemia: 81 ± 3). Histopathological evaluations revealed the presence of a local infiltrate of mast cells in the area of ischaemia (nb of mast cells: 142 ± 50; P < 0.05 vs. control, 31 ± 14 or sham ischaemia: 40 ± 16), without other significant alterations. Animals subjected to colonic ischaemia and treated 8 weeks later with the mast cell degranulator, compound 48/80, showed no changes in CRD-related pain responses. These studies show that acute colonic ischaemia is associated with the presence of a long-term local infiltration of mast cells, located within the serosa and muscle layers, despite the absence of functional changes, including colonic sensitivity. Considering the important pathophysiological functions of mast cells, the observed mast cell infiltration may be involved in ischaemia-induced functional changes yet to be characterized. PMID:19134057

  12. Aspirin failure in patients presenting with acute cerebrovascular ischaemia.

    PubMed

    Halawani, Saeed H M; Williams, David J P; Adefurin, Abiodun; Webster, John; Greaves, Michael; Ford, Isobel

    2011-08-01

    Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention. PMID:21544317

  13. Successful Treatment of Acute on Chronic Mesenteric Ischaemia by Common Iliac to Inferior Mesenteric Artery Bypass

    PubMed Central

    Coakley, D. N.; Shaikh, F. M.; Kavanagh, E. G.

    2015-01-01

    Chronic mesenteric ischaemia is a rare and potentially fatal condition most commonly due to atherosclerotic stenosis or occlusion of two or more mesenteric arteries. Multivessel revascularisation of both primary mesenteric vessels, the celiac artery and superior mesenteric artery (SMA), is the current mainstay of treatment; however, in a certain cohort of patients, revascularisation one or both vessels may not be possible. Arteries may be technically unreconstructable or the patient may be surgically unfit for the prolonged aortic cross clamping times required. Here we present a case involving a 72-year-old woman with acute on chronic mesenteric ischaemia. She was a high risk surgical patient with severe unreconstructable stenotic disease of the SMA and celiac arteries. She was successfully treated with single vessel revascularisation of the inferior mesenteric artery (IMA) via a common iliac to IMA reversed vein bypass. At two-year follow-up, the graft remains patent and the patient continues to be symptom-free and is maintaining her weight. PMID:26421207

  14. The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice.

    PubMed

    Yagihashi, Soroku; Mizukami, Hiroki; Ogasawara, Saori; Yamagishi, Shin-Ichiro; Nukada, Hitoshi; Kato, Noriaki; Hibi, Chihiro; Chung, Sookja; Chung, Stephen

    2010-04-01

    The polyol pathway, a collateral glycolytic process, previously considered to be active in high glucose milieu, has recently been proposed to play a crucial role in ischaemia/reperfusion tissue injury. In this study, we explored the role of the polyol pathway in acute kidney injury (AKI), a life-threatening condition, caused by hindlimb ischaemia, and determined if inhibition of the polyol pathway by aldose reductase (AR) inhibitor is beneficial for this serious disorder. Mice 8 weeks of age rendered hindlimb ischaemic for 3 h by the clipping of major supporting arteries revealed marked muscle necrosis with accumulation of sorbitol and fructose in ischaemic muscles. Serum concentrations of blood urea nitrogen (BUN), creatinine phosphokinase (CPK), creatinine, tumour necrosis factor (TNF)-alpha as well as interleukin (IL)-6 were all elevated in these mice. Treatment with AR inhibitor (ARI) effectively suppressed muscle necrosis and accompanying inflammatory reactions and prevented renal failure. Similar to ARI-treated mice, AR-deficient mice were protected from severe ischaemic limb injury and renal failure, showing only modest muscle necrosis and significant suppression of serum markers of renal failure and inflammation. Thus, these findings suggest that the polyol pathway is implicated in AKI caused by ischaemic limb injury and that AR may be a potential therapeutic target for this condition. PMID:20112370

  15. Acute intestinal anisakiasis: CT findings.

    PubMed

    Ozcan, H N; Avcu, S; Pauwels, W; Mortelé, K J; De Backer, A I

    2012-09-01

    Small bowel anisakiasis is a relatively uncommon disease that results from consumption of raw or insufficiently pickled, salted, smoked, or cooked wild marine fish infected with Anisakis larvae. We report a case of intestinal anisakiasis in a 63-year-old woman presenting with acute onset of abdominal complaints one day after ingestion of raw wild-caught herring from the Northsea. Computed tomography (CT) scanning demonstrated thickening of the distal small bowel wall, mucosa with hyperenhancement, mural stratification, fluid accumulation within dilated small-bowel loops and hyperemia of mesenteric vessels. In patients with a recent history of eating raw marine fish presenting with acute onset of abdominal complaints and CT features of acute small bowel inflammation the possibility of anisakiasis should be considered in the differential diagnosis of acute abdominal syndromes.

  16. Influence of local peripheral temporary ischaemia on biochemical and histological effects in small intestine and serum of rats following abdominal irradiation.

    PubMed

    Przybyszewski, W M; Walichiewicz, P; Widel, M; Polaniak, R; Snietura, M; Maniakowski, Z; Jacheć, W

    2008-01-01

    The local temporary ischaemia effect on radiation-induced lipid peroxidation, superoxide dismutase isoenzyme activities, and intestinal crypt number was estimated in male WAG-strain rats in vivo. The animals were irradiated in the abdomen area with doses of 2 Gy for ten consecutive days using a Philips 60Co source. The calculated dose rate was 0.595 Gy/min. Local temporary ischaemia was induced by clamping the tail base before each irradiation. The parameters evaluated were: TBA-RS level and enzymatic activities of CuZnSOD, MnSOD in serum and jejunum. The number of jejunum crypts was assigned as a histopathologic parameter. The results showed a clear protection by ischaemic preconditioning for crypt survival. The difference in the number of crypts in irradiated animals with and without local temporary ischaemia was statistically significant (Student's t-test P < 0.05). Also, significant enhancement of TBA-RS was observed in the serum of irradiated animals. Local temporary ischaemia application diminished the concentration of radiation- induced TBA-RS. The differences in the levels of TBA-RS in the serum were statistically significant (ANOVA P < 0.002). In contrast, there was no evident effect on the level of TBA-RS in tissue homogenates in any investigated groups. Some fluctuation of CuZnSOD isoenzyme activity in intestinal tissue was noted; however, the differences were not significant. Local temporary ischaemia had no influence on Mn- SOD activity in serum, and in both irradiated groups the behaviour of this isoenzyme was similar. Also, there were no differences in MnSOD activity measured in tissue homogenates. These findings support results of our previous in vivo studies, suggesting that local temporary ischaemia can prevent oxidative effects of fractionated radiotherapy. PMID:19393129

  17. Run-down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat.

    PubMed Central

    Harata, N; Wu, J; Ishibashi, H; Ono, K; Akaike, N

    1997-01-01

    1. The effect of experimental ischaemia on the response to gamma-aminobutyric acid (GABA) was assessed in acutely dissociated CA1 pyramidal neurones of rats, using the patch-clamp technique. 2. Rapid application of 3 x 10(-5) M GABA induced a bicuculline-sensitive inward Cl- current (IGABA) at a holding potential (Vh) of -44 mV. The peak amplitude of IGABA showed a time-dependent decrease (run-down) when it was recorded with the conventional whole-cell mode without internal ATP. The run-down was not observed when the intracellular ATP concentration ([ATP]i) was maintained by the nystatin-perforated recording with an intracellular Na+ concentration ([Na+]i) of 0 mM. 3. When [Na+]i was increased to more than 30 mM, the IGABA run-down was observed even with the nystatin-perforated recording. 4. The IGABA run-down observed at 60 mM [Na+]i with the nystatin method was further enhanced under experimental ischaemia without changes in the reversal potential of IGABA. The enhanced run-down was suppressed by application of the Na+,K(+)-ATPase inhibitors, ouabain and SPAI-1. 5. IGABA run-down during ischaemia was also accompanied by an outward holding current and a concomitant increase in intracellular free Ca2+ concentration ([Ca2+]i) in 48.5% of the neurones. The outward current was a Ca(2+)-activated K+ current, which was blocked by 3 x 10(-7) M charybdotoxin. 6. In the inside-out mode of the single-channel analysis, GABA activated three subconductance states with conductances of 33.4, 22.7 and 15.2 pS. Reduction of ATP concentration from 2 to 0 mM on the intracellular side suppressed the channel activities, while an increase in Ca2+ concentration from 0.7 x 10(-9) to 1.1 x 10(-6) M had no effect. 7. These results suggest that ischaemia induces the run-down of the postsynaptic GABA response at the GABAA receptor level, and that this run-down is triggered by a decrease in [ATP]i. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9161985

  18. Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig.

    PubMed Central

    Dilly, S G; Lab, M J

    1988-01-01

    1. Alternate long and short action potential durations, or electrical alternans, has only been sporadically observed in ischaemic myocardium in situ. We systematically studied alternans in the latter to characterize the phenomenon, relate it to ventricular arrhythmia and suggest possible mechanisms. 2. Sixteen Landrace pigs were anaesthetized (Azaperone, N2O and O2), ventilated and the hearts exposed. A branch of the left coronary artery was ligated. Left intraventricular and systemic pressures were monitored. Monophasic action potentials were recorded simultaneously with up to five suction electrodes in and around the proposed ischaemia area. 3. A computer measured the duration of every action potential, at several phases of repolarization, throughout the first hour of ischaemia. This allowed the systematic study of the alternans. Measurements during defined stimulus protocols were also made for the construction of electrical restitution curves. 4. Alternans was found in all recordings within the ischaemic area and in two-thirds of those in the 'border' area. There was no alternans in non-ischaemic areas. 5. The alternans, when action potential duration was plotted for every beat, appeared as an oscillation which was pleomorphic. It could be: (a) stable for hundreds of beats; (b) switched or triggered (by one extraneous beat having a different cycle length) between one stable state with high and one with low or absent alternans; (c) damped; (d) undamped to take a crescendo form, sometimes preceding ventricular fibrillation. 6. The alternans in general showed an ill-defined peak incidence between about 200 to 1500 beats after the onset of ischaemia, and a clearer late peak at about 3000 beats. These periods occurred at about 2-7 min and 15-40 min, corresponding to so-called phase 1A and 1B arrhythmia respectively. Only the late peak was seen with triggered alternans. 7. The electrical restitution curve for the action potential duration during ischaemia when

  19. Mechanisms of the anti-inflammatory effects of the natural secosteroids physalins in a model of intestinal ischaemia and reperfusion injury

    PubMed Central

    Vieira, Angélica T; Pinho, Vanessa; Lepsch, Lucilia B; Scavone, Cristóforo; Ribeiro, Ivone M; Tomassini, Therezinha; Ribeiro-dos-Santos, Ricardo; Soares, Milena B P; Teixeira, Mauro M; Souza, Danielle G

    2005-01-01

    Reperfusion of an ischaemic tissue is associated with an intense inflammatory response and inflammation-mediated tissue injury. Physalins, a group of substances with secosteroidal chemical structure, are found in Physalis angulata stems and leaves. Here, we assessed the effects of physalins on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in mice and compared with the effects of dexamethasone. Following I/R injury, dexamethasone (10 mg kg−1) or physalin B or F markedly prevented neutrophil influx, the increase in vascular permeability in the intestine and the lungs. Maximal inhibition occurred at 20 mg kg−1. Moreover, there was prevention of haemorrhage in the intestine of reperfused animals. Dexamethasone or physalins effectively suppressed the increase in tissue (intestine and lungs) and serum concentrations of TNF-α. Interestingly, treatment with the compounds was associated with enhancement of IL-10. The anti-inflammatory effects of dexamethasone or physalins were reversed by pretreatment with the corticoid receptor antagonist RU486 (25 mg kg−1). The drug compounds suppressed steady-state concentrations of corticosterone, but did not alter the reperfusion-associated increase in levels of corticosterone. The IL-10-enhancing effects of the drugs were not altered by RU486. In conclusion, the in vivo anti-inflammatory actions of physalins, natural steroidal compounds, appear to be mostly due to the activation of glucocorticoid receptors. Compounds derived from these natural secosteroids may represent novel therapeutic options for the treatment of inflammatory diseases. PMID:16025143

  20. Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia

    PubMed Central

    Li, Hailong; Zhang, Nannan; Sun, Grace; Ding, Shinghua

    2013-01-01

    Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine] or mGluR1 antagonist LY367385 by intraperitoneal injection at 3 h after PT decreased brain infarct volume evaluated one day after ischaemia. Additive effects on infarct volume were observed upon co-injection with MPEP and LY367385. These antagonists also significantly alleviated neurodegeneration and apoptosis in the penumbra. In addition, when evaluated 2 weeks after PT, they reduced infarct volume and tissue loss, attenuated glial scar formation, and inhibited cell proliferation in the penumbra. Importantly, co-injection with MPEP and LY367385 reduced the expression levels of calpain, a Ca2+-activated protease known to mediate ischaemia-induced neuronal death. Injection of calpeptin, a calpain inhibitor, could inhibit neuronal death and brain damage after PT but injection of calpeptin together with MPEP and LY367385 did not further improve the protective effects mediated by MPEP and LY367385. These results suggest that inhibition of group I mGluRs is sufficient to protect ischaemic damage through the calpain pathway. Taken together, our results demonstrate that inhibition of group I mGluRs can mitigate PT-induced brain damage through attenuating the effects of calpain, and improve long-term histological outcomes. PMID:23772679

  1. Lidocaine and structure-related mexiletine induce similar contractility-enhancing effects in ischaemia-reperfusion injured equine intestinal smooth muscle in vitro.

    PubMed

    Tappenbeck, Karen; Hoppe, Susanne; Hopster, Klaus; Kietzmann, Manfred; Feige, Karsten; Huber, Korinna

    2013-06-01

    Postoperative ileus (POI) is a severe complication following small intestinal surgery in horses. It was hypothesised that prokinetic effects of lidocaine, the most commonly chosen drug for treatment of POI, resulted from drug integration into smooth muscle (SM) cell membranes, thereby modulating cell membrane properties. This would probably depend on the structural and lipophilic characteristics of lidocaine. To assess the influence of molecular structure and lipophilicity on prokinetic effects in vitro, the current study compared the effects of lidocaine with four structure-related drugs, namely, mexiletine, bupivacaine, tetracaine and procaine. The response to cumulative drug administration and reversibility of effects were tested by measuring isometric contractile performance of equine jejunal circular SM strips, challenged by a standardised, artificial in vivo ischaemia-reperfusion injury. A second set of SM strips were incubated with the different drugs to determine changes in creatine kinase (CK) release. All drugs caused a drug-specific increase in contractility, although only lidocaine and mexiletine induced similar concentration-dependent curve progressions, significantly reduced CK release, and featured shorter recovery times of tissue contractility after washing, compared to bupivacaine and tetracaine. In was concluded that the structural and lipophilic similarity of mexiletine and lidocaine were responsible for the similar effects of these drugs on SM contractility and cell membrane permeability, which supported the hypothesis that prokinetic effects of lidocaine are based on interactions with SM cell membranes modulated by these features. PMID:23265867

  2. Intestinal permeability in patients with acute myeloid leukemia.

    PubMed

    Sundström, G M; Wahlin, A; Nordin-Andersson, I; Suhr, O B

    1998-10-01

    Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

  3. Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation

    PubMed Central

    Progatzky, Fränze; Sangha, Navjyot J.; Yoshida, Nagisa; McBrien, Marie; Cheung, Jackie; Shia, Alice; Scott, James; Marchesi, Julian R.; Lamb, Jonathan R.; Bugeon, Laurence; Dallman, Margaret J.

    2014-01-01

    Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells. PMID:25536194

  4. Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation.

    PubMed

    Progatzky, Fränze; Sangha, Navjyot J; Yoshida, Nagisa; McBrien, Marie; Cheung, Jackie; Shia, Alice; Scott, James; Marchesi, Julian R; Lamb, Jonathan R; Bugeon, Laurence; Dallman, Margaret J

    2014-01-01

    Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells. PMID:25536194

  5. Acute abdomen in adult Celiac disease: an intestinal intussusception case.

    PubMed

    Makay, Ozer; Kazimi, Mircelal; Doğanavşargil, Başak; Osmanoğlu, Necla; Yilmaz, Mustafa

    2007-06-01

    It is well known that half of the cases admitted to hospital emergency services complain of abdominal pain and that nearly half of these cases are diagnosed with nonspecific abdominal pain. The population of patients with celiac sprue is rarely encountered at the emergency room. Although acute abdominal pain is rarely seen in adult celiac sprue, it should be added to the differential diagnosis. It should also be remembered that acute abdominal pain in these patients could be originating from perforation, intussusceptions and/or intestinal lymphoma. Herein we report a case of adult celiac sprue where successful surgical exploration was carried out because of entero-enteral intussusception. PMID:17602358

  6. The activation of PI 3-kinase/Akt pathway is involved in the acute effects of simvastatin against ischaemia and reperfusion-induced arrhythmias in anaesthetised dogs.

    PubMed

    Kisvári, Gábor; Kovács, Mária; Seprényi, György; Végh, Ágnes

    2015-12-15

    The objective of this study was to examine whether the PI3-kinase/Akt pathway is involved in the activation of endothelial nitric oxide synthase (eNOS) and in the subsequent increase of nitric oxide (NO) production that has been proved to play a role in the antiarrhythmic effect of acute simvastatin treatment in anaesthetised dogs, subjected to a 25min occlusion and reperfusion of the left anterior descending coronary artery. Using the same model, 12 dogs out of the 26 controls (given the solvent of simvastatin) and 11 dogs out of the 23 animals treated with intracoronary administered simvastatin (0.1mg/kg), were now received wortmannin (1.5mg/kg, ic.), a selective inhibitor of PI3-kinase. In another 13 dogs the effects of DMSO (0.1%), the vehicle of wortmannin, were examined. Compared to the controls, simvastatin markedly reduced the severity of ischaemia (epicardial ST-segment, inhomogeneity) and ventricular arrhythmias that were reversed (except the occlusion-induced ventricular fibrillation [VF; 50%, 0%, 0%]) by the administration of wortmannin. Thus in these groups there were 310±45, 62±14, 307±59 ectopic beats, 7.1±1.4, 0.3± 0.2, 4.3±1.3 tachycardiac episodes that occurred 93%, 17% and 73% of the dogs during occlusion, whereas survival following reperfusion was 0%, 67% and 0%, respectively. Simvastatin also increased the phosphorylation of eNOS and the plasma nitrate/nitrite levels, but reduced myocardial superoxide production on reperfusion. These effects of simvastatin were also abolished in the presence of wortmannin. We conclude that the NO-dependent antiarrhythmic effect of simvastatin involves the rapid activation of eNOS through the stimulation of the PI3-kinase/Akt pathway.

  7. Dynamics of Urinary Calprotectin after Renal Ischaemia

    PubMed Central

    Ebbing, Jan; Seibert, Felix S.; Pagonas, Nikolaos; Bauer, Frederic; Miller, Kurt; Kempkensteffen, Carsten; Günzel, Karsten; Bachmann, Alexander; Seifert, Hans H.; Rentsch, Cyrill A.; Ardelt, Peter; Wetterauer, Christian; Amico, Patrizia; Babel, Nina; Westhoff, Timm H.

    2016-01-01

    Background: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase—associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. Methods: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5–20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase—associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. Results: Urinary concentrations of calprotectin and neutrophil gelatinase—associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase—associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase—associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia

  8. Prognostic factors in extensive mesenteric ischaemia.

    PubMed Central

    Gorey, T. F.; O'Sullivan, M.

    1988-01-01

    The records of 65 patients with diagnoses of extensive intestinal ischaemia during the 10 years from December 1973 to January 1984 were retrieved from 18 hospitals in Ireland. There were 32 males and 33 females, ranging in age from 20 to 96 years (mean 69.8 years). Duration of symptoms ranged from 4 h to 8 days. Pain was the most common presenting feature. Gastrointestinal haemorrhage was apparent in 31%, hypotension in 28% and atrial fibrillation in 43%. Associated vascular disease was present in 43%. There were elevations of serum inorganic phosphate in 15%, leucoytosis in 65% and metabolic acidosis in 67%. The mean interval from hospital admission to operation in survivors was 14.5 h, whereas the mean delay in those who died was 44 h. The correct preoperative diagnosis was made in 23 (35%) and the aetiology of intestinal ischaemia was recorded as: thrombosis 25 (39%), embolism 12 (18%), adhesions/volvulus 4 (6%) and indeterminate in 24 (37%). Laparotomy was performed in 49: gangrenous bowel was resected in 29 and six had operations designed to revascularise the intestine. The remaining 14 patients either had laparotomy alone (12) or an inappropriate operation (2). In 46 patients (70.8%) who died, death was related to three factors: the mean age of survivors was 7 years less than that of patients who died, the interval to laparotomy was on average 30 h less, and the length of ischaemic bowel was on average 61% less. PMID:3415165

  9. How critical is chronic critical leg ischaemia?

    PubMed

    Kroese, A J; Stranden, E

    1998-01-01

    "Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added. PMID:9676324

  10. How critical is chronic critical leg ischaemia?

    PubMed

    Kroese, A J; Stranden, E

    1998-01-01

    "Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added.

  11. Preoperative myocardial ischaemia: its relation to perioperative infarction.

    PubMed Central

    Yousif, H; Davies, G; Westaby, S; Prendiville, O F; Sapsford, R N; Oakley, C M

    1987-01-01

    One hundred consecutive patients undergoing coronary artery bypass surgery were randomly allocated to a preoperative (24 h) intravenous infusion of isosorbide dinitrate (1.5-15 mg/hr) (50 patients) or to placebo (50 patients). The characteristics of the two groups were similar. Evidence of acute myocardial ischaemia was sought by continuous electrocardiographic Holter recordings and acute myocardial infarction by the appearance of new Q waves and increased activity of the creatine kinase MB isoenzyme. Episodes of acute myocardial ischaemia were found in 18% of patients in the control group and in none of those who received isosorbide dinitrate. None the less, the frequency of perioperative myocardial infarction was similar (22% and 18% respectively) in the two groups. Perioperative infarction was significantly more common in women, in patients with unstable angina or poor left ventricular function, in those who had coronary endarterectomy, and in those in whom the aortic clamping time was greater than 50 minutes. These factors may have obscured any effect that prevention of preoperative ischaemia had on perioperative infarction. Preoperative infusion of isosorbide dinitrate eliminated preoperative ischaemia but did not influence the occurrence of perioperative infarction. The probable benefits of prevention of preoperative ischaemia on postoperative left ventricular function, which is a determinant of long term survival, remain to be established. PMID:3304371

  12. Accuracy of the serum intestinal fatty-acid-binding protein for diagnosis of acute intestinal ischemia: a meta-analysis

    PubMed Central

    Sun, Da-Li; Cen, Yun-Yun; Li, Shu-Min; Li, Wei-Ming; Lu, Qi-Ping; Xu, Peng-Yuan

    2016-01-01

    Numerous studies have investigated the utility of serum intestinal fatty-acid binding protein (I-FABP) in differentiating acute intestinal ischemia from acute abdomen. However, the results remain controversial. The aim of this meta-analysis is to determine the overall accuracy of serum I-FABP in the diagnosis of acute intestinal ischemia. Publications addressing the accuracy of serum I-FABP in the diagnosis of ischemic bowel diseases were selected from databases. The values of true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The overall diagnostic performance was assessed using a summary receiver operating characteristic curve (SROC) and area under curve (AUC). Nine studies that collectively included 1246 patients met the eligible criteria. The pooled sensitivity, specificity, DOR, PLR, and NLR were 0.80 (95% CI: 0.72–0.86), 0.85 (95% CI: 0.73–0.93), 24 (95% CI: 9–65), 5.5 (95% CI: 2.8–10.8) and 0.23 (95% CI: 0.15–0.35), respectively. The AUC was 0.86 (95% CI: 0.83–0.89). The meta-analysis carried out in this report suggests that the I-FABP may be a useful diagnostic tool to confirm acute intestinal ischemia in acute abdomen, but better-designed trials are still required to confirm our findings. PMID:27681959

  13. The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide?

    PubMed

    Kisvári, Gábor; Kovács, Mária; Gardi, János; Seprényi, György; Kaszaki, József; Végh, Ágnes

    2014-06-01

    The present study has examined the effects and the possible mechanisms of a single dose of simvastatin on the severity of arrhythmias resulting from a 25min occlusion and reperfusion of the left anterior descending coronary artery in anaesthetized (chloralose and urethane) dogs. The control animals (n=16) were given the solvent of simvastatin by slow (over 5min) intracoronary (ic.) injection just prior to the occlusion. Twenty-six dogs were treated with simvastatin (0.1mg/kg) by the same route, both in the absence (n=15) and in the presence (n=11) of l-NAME. This latter was administered (5mg/kg, ic.) either alone (n=12) or 10min before the simvastatin treatment. The severity of ischaemia (epicardial ST-segment, inhomogeneity) and ventricular arrhythmias (ventricular premature beats [VPBs], ventricular tachycardia [VT] and fibrillation [VF]), plasma nitrite/nitrate levels, myocardial superoxide production and eNOS activity were assessed. Compared with controls simvastatin significantly reduced the number of VPBs (289±34vs. 94±25) and the episodes of VT (5.6±1.3vs. 0.3±0.2), the incidence of VT (88% vs. 20%) and VF (56% vs. 0%) during occlusion and increased survival (0% vs. 33%) on reperfusion. There were also less marked ischaemic changes in the simvastatin-treated dogs than in the controls. Simvastatin preserved eNOS activity and nitric oxide (NO) bioavailability during occlusion and attenuated superoxide production following reperfusion. All these effects of simvastatin (except for the protection against VF) were reversed by l-NAME. We conclude that simvastatin given just prior to ischaemia/reperfusion reduces the severity of arrhythmias. This effect involves both NO-dependent and NO-independent mechanisms. PMID:24685640

  14. [Acute intestinal obstruction revealing enteropathy associated t-cell lymphoma, about a case].

    PubMed

    Garba, Abdoul Aziz; Adamou, Harissou; Magagi, Ibrahim Amadou; Brah, Souleymane; Habou, Oumarou

    2016-01-01

    Enteropathy associated T-cell lymphoma (EATL) is a rare complication of celiac disease (CD). We report a case of EATL associated with CD revealed by acute intestinal obstruction. A North African woman of 38 years old with a history of infertility and chronic abdominal pain was admitted in emergency with acute intestinal obstruction. During the surgery, we found a tumor on the small intestine with mesenteric lymphadenopathy. Histology and immunohistochemistry of the specimen objectified a digestive T lymphoma CD3+ and immunological assessment of celiac disease was positive. The diagnosis of EATL was thus retained. Chemotherapy (CHOEP protocol) was established as well as gluten-free diet with a complete response to treatment. The EATL is a rare complication of CD that can be revealed by intestinal obstruction. The prognosis can be improved by early treatment involving surgery and chemotherapy. Its prevention requires early diagnosis of celiac and gluten-free diets. PMID:27217874

  15. Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice

    PubMed Central

    Zhu, Qiankun; He, Guizhen; Wang, Jie; Wang, Yukang; Chen, Wei

    2016-01-01

    This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI. PMID:26902261

  16. Acute intestinal obstruction due to a non-involuted uterus after cesarean section: case report.

    PubMed

    Karaman, K; Ercan, M; Demir, H; Yener Uzunoglu, M; Bostanci, S

    2016-01-01

    The involution of the uterus is influenced by a number of factors such as advanced childbearing age, electrolyte disturbances, multiparity, repeated cesarean sections, and vaginal infections. The authors report the management of a clinical case of a 41-year-old female who presented with acute intestinal obstruction due to a non-involuted uterus after cesarean section.

  17. Acute uremia and intestinal obstruction due to a retroperitoneal hydatid cyst.

    PubMed

    Yilmaz, Mehmet; Ugraş, Murat; Işik, Burak; Yilmaz, Sezai; Kirimlioğlu, Vedat

    2007-12-01

    Hydatid disease should be considered in the differential diagnosis of any cystic mass in endemic areas. The symptoms due to bulk effect, usually occurring over a certain period of time, depend on the site and size of the cyst. We report an unusual presentation of retroperitoneal hydatid cyst with rapidly developing uremia and acute intestinal obstruction.

  18. The hydrocortisone protection of glycocalyx on the intestinal capillary endothelium during severe acute pancreatitis.

    PubMed

    Gao, Shun-Liang; Zhang, Yun; Zhang, Shao-Yang; Liang, Zhong-Yan; Yu, Wen-Qiao; Liang, Ting-Bo

    2015-05-01

    Malfunctioning of the intestinal microcirculation secondary to severe acute pancreatitis (SAP) can cause injuries to the intestinal mucosal barrier, translocation of gut flora, and sepsis. The glycocalyx on the vascular endothelium helps maintain its normal function through multiple mechanisms, including regulation of vascular permeability and inhibition of intercellular adhesion. It is unknown that whether pancreatitis inflicts injuries to the intestinal mucosal barrier through damaging glycocalyx or stabilizing glycocalyx can be a potential therapeutic target in maintaining the integrity of the intestinal mucosal barrier during SAP. Injecting sodium taurocholate into the pancreatic duct of Sprague-Dawley rats induced SAP. Intestinal perfusion, changes in endothelial glycocalyx, and the associated molecular mechanisms were assessed by laser Doppler velocimetry, electron microscopy, and the levels of heparan sulfate, syndacan-1, and tumor necrosis factor-α (TNF-α) in the superior mesenteric vein. Protective effects of hydrocortisone treatment in the intestinal microcirculation during SAP were evaluated. Degradation of the glycocalyx in intestinal vascular endothelium developed 3 h after the onset of SAP in rats. By 12 h, significant reduction of intestinal perfusion was observed. The concomitant elevated levels of TNF-α in the superior mesenteric vein suggest that TNF-α is involved in the degradation of the glycocalyx. With the use of hydrocortisone, intestinal perfusion was improved and the degradation of glycocalyx was reduced. The degradation of glycocalyx is involved in the malfunction of the intestinal microcirculation. The massive release of TNF-α participates in this process and leads to glycocalyx degradation. Hydrocortisone may be a good therapy to prevent this process.

  19. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  20. Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.

    PubMed

    Hirano, Yohei; Aziz, Monowar; Yang, Weng-Lang; Ochani, Mahendar; Wang, Ping

    2016-10-01

    Intestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome. Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). Intestinal I/R was induced in mice by superior mesenteric artery occlusion with a vascular clip. After 45 min of occlusion, the clip was removed and anti-OPN Ab (25 μg/mouse) or normal IgG isotype control (25 μg/mouse) was immediately administrated intravenously. Blood, small intestine, and lung tissues were collected at 4 h after reperfusion for various analyses. After intestinal I/R, mRNA and protein levels of OPN were significantly induced in the small intestine, lungs, and blood relative to sham-operated animals. Compared with the IgG control group, treatment of anti-OPN Ab significantly reduced plasma levels of pro-inflammatory cytokine and chemokine (IL-6 and MIP-2) and organ injury markers (AST, ALT, and LDH). The histological architecture of the gut and lung tissues in anti-OPN Ab-treated intestinal I/R-induced mice showed significant improvement versus the IgG control mice. The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R. PMID:26974422

  1. Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.

    PubMed

    Hirano, Yohei; Aziz, Monowar; Yang, Weng-Lang; Ochani, Mahendar; Wang, Ping

    2016-10-01

    Intestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome. Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). Intestinal I/R was induced in mice by superior mesenteric artery occlusion with a vascular clip. After 45 min of occlusion, the clip was removed and anti-OPN Ab (25 μg/mouse) or normal IgG isotype control (25 μg/mouse) was immediately administrated intravenously. Blood, small intestine, and lung tissues were collected at 4 h after reperfusion for various analyses. After intestinal I/R, mRNA and protein levels of OPN were significantly induced in the small intestine, lungs, and blood relative to sham-operated animals. Compared with the IgG control group, treatment of anti-OPN Ab significantly reduced plasma levels of pro-inflammatory cytokine and chemokine (IL-6 and MIP-2) and organ injury markers (AST, ALT, and LDH). The histological architecture of the gut and lung tissues in anti-OPN Ab-treated intestinal I/R-induced mice showed significant improvement versus the IgG control mice. The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R.

  2. Survival after intestinal mucormycosis in acute myelogenous leukemia.

    PubMed

    Parra, R; Arnau, E; Julia, A; Lopez, A; Nadal, A; Allende, E

    1986-12-15

    A young woman with acute myelocytic leukemia developed acute lower gastrointestinal bleeding immediately after a first remission induction of her leukemia. After the site of bleeding was located in the descending colon, a necrotic bleeding ulcer was resected. Histologic examination of the ulcer established the diagnosis of gastrointestinal mucormycosis. Treatment with amphotericin B was administered because of the high risk of dissemination. The patient has been followed for 9 months with no evidence of relapse of infection. Survival after gastrointestinal mucormycosis in acute leukemia has not previously been reported in the English language literature. Success in managing mucormycosis depends on the adherence to the recommended principles of early aggressive diagnostic measures, excisional surgery, amphotericin B therapy, and control of the underlying predisposing condition.

  3. 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

  4. Cerebrovascular ischaemia after carbon monoxide intoxication.

    PubMed

    Kara, Hasan; Bayir, A; Ak, Ahmet; Degirmenci, Selim

    2015-02-01

    Carbon monoxide intoxication is the most prevalent cause of death from carbon monoxide poisoning. We herein report the case of a 56-year-old man who was found unconscious and smelled of smoke after exposure to carbon monoxide from a heater. He scored 5 on the Glasgow Coma Scale, and had respiratory insufficiency and elevated troponin I, creatine kinase-MB fraction and carboxyhaemoglobin levels. He was treated by mechanical ventilation. After regaining consciousness, brain magnetic resonance imaging showed diffusion restriction in the left occipital lobe; there was a loss of vision (right temporal hemianopsia), which improved by the follow-up session. Carbon monoxide intoxication may cause neurologic and cardiac sequelae, and the initial treatment includes oxygen therapy. Acute carbon monoxide poisoning can cause serious injury to the brain, heart and other organs; the most severe damages that could be inflicted to the brain include cerebral ischaemia and hypoxia, oedema, and neural cell degeneration and necrosis. PMID:25715861

  5. Cerebrovascular ischaemia after carbon monoxide intoxication.

    PubMed

    Kara, Hasan; Bayir, A; Ak, Ahmet; Degirmenci, Selim

    2015-02-01

    Carbon monoxide intoxication is the most prevalent cause of death from carbon monoxide poisoning. We herein report the case of a 56-year-old man who was found unconscious and smelled of smoke after exposure to carbon monoxide from a heater. He scored 5 on the Glasgow Coma Scale, and had respiratory insufficiency and elevated troponin I, creatine kinase-MB fraction and carboxyhaemoglobin levels. He was treated by mechanical ventilation. After regaining consciousness, brain magnetic resonance imaging showed diffusion restriction in the left occipital lobe; there was a loss of vision (right temporal hemianopsia), which improved by the follow-up session. Carbon monoxide intoxication may cause neurologic and cardiac sequelae, and the initial treatment includes oxygen therapy. Acute carbon monoxide poisoning can cause serious injury to the brain, heart and other organs; the most severe damages that could be inflicted to the brain include cerebral ischaemia and hypoxia, oedema, and neural cell degeneration and necrosis.

  6. Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

    PubMed Central

    Parrilli, G; Cuomo, R; Nardone, G; Maio, G; Izzo, C M; Budillon, G

    1987-01-01

    One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention. PMID:3428669

  7. [Intestinal tuberculosis--cause of acute surgical abdomen].

    PubMed

    Ciurea, M; Ion, D; Ionescu, S; Tica, M R

    2001-01-01

    Tuberculosis, in its various forms, remains an important cause of morbidity and mortality in developing countries in immunodeficitary patients. The indicatives of epidemiology of tuberculosis show that Romania presents a fresh outbreak of the disease in the last few years. The purpose of this paper is to present from the various forms of extrapulmonary tuberculosis, the intestinal tipe which have a high incidence. The authors describe theirs preliminary experience of intraoperative small and large bowel emergencies resections in a short period (1 year) of three young patients (between 30 and 40 years old) with history of pulmonary tuberculosis. The pathology was complex (bowel obstructions, peritonitis) and so were the surgical operations (resections, devirations). The patients showed short and long term good results.

  8. Intestinal Schistosomiasis as Unusual Aetiology for Acute Appendicitis, Nowadays a Rising Disease in Western Countries

    PubMed Central

    López de Cenarruzabeitia, I.; Landolfi, S.; Armengol Carrasco, M.

    2012-01-01

    Intestinal schistosomiasis as unusual aetiology for acute appendicitis, nowadays a rising disease in western countries. Recent changes in global migration has led to an immigration growth in our scenario, upsurging people coming from endemic areas of schistosomiasis. Schistosomal appendicitis, seldom reported in developed countries, is now an expected incrising entity in our hospitals during the near future. Due to this circumstances, we believe that schistosomiasis should be consider as a rising source for acute appendicitis in western countries. In order to illustrate this point, we present a case of a 45-years-old black man, from Africa, was admitted via A&E because of acute abdominal pain, located in right lower quadrant. Acute appendicitis was suspected, and he underwent laparotomy and appendectomy. Pathological study by microscope revealed a gangrenous appendix with abscesses and parasitic ova into the submucosal layer of the appendix, suggesting Schistosomiasis. PMID:22792502

  9. Idiopathic myenteric ganglionitis underlying acute 'dramatic' intestinal pseudoobstruction: report of an exceptional case.

    PubMed

    Racalbuto, A; Magro, G; Lanteri, R; Aliotta, I; Santangelo, M; Di Cataldo, A

    2008-09-01

    Inflammation of the myenteric plexus of the gastrointestinal tract is a very rare pathological condition, with few reports in the medical literature. This pathological condition causes atonic gut motor dysfunction and is principally secondary to other diseases, being reported nearly solely as a paraneoplastic phenomenon in neuroendocrine lung tumors, including small cell carcinomas or neuroblastomas. In addition it can also be associated with disorders of the central nervous system, although it has rarely been described in Chagas disease. It has been named 'idiopathic myenteric ganglionitis' because no apparent causes can be demonstrated. We report the clinicopathologic findings of an exceptional case of a young woman affected by severe chronic constipation suddenly changing into acute intestinal pseudoobstruction with dramatic evolution. Relationships between ganglionitis, idiopathic constipation and acute intestinal pseudoobstruction as well as therapeutic implications are discussed.

  10. Surgical treatment of acute myocardial ischaemia related to coronary angioplasty with special reference to use of perfusion balloon catheter and long-term outcome.

    PubMed

    Heikkinen, L; Virtanen, K; Heikkila, J; Verkkala, K; Salo, J; Jarvinen, A

    1997-04-01

    Twenty of 569 consecutive patients (3.5%) undergoing percutaneous transluminal coronary angioplasty required emergency coronary artery bypass grafting for acute closure of the dilated vessel. In seven patients an intracoronary autoperfusion balloon catheter was inserted to ensure antegrade blood flow across the injured zone of the coronary artery. The time needed for completion of the bypass grafts ranged from 100 to 399 minutes (mean 180 minutes). An average of 1.9 coronary artery bypasses was inserted. In total, 11 of the 20 patients (55%) developed new Q waves and had elevated CK-MB levels. However, the myocardial infarction rate was only 14% in those with a perfusion balloon catheter as against 77% in those without one. The insertion of a ball-out catheter permitted greater utilization of the internal mammary artery as a bypass graft. Angiographic follow-up was conducted after a mean of 28 months (19 patients). The patency rate of the bypass grafts placed in the emergency setting was relatively good (91%). Thallium tomography revealed a scar of variable size in all 17 patients studied and a reversible exercise perfusion defect requiring coronary reangioplasty in three patients. In conclusion, the insertion of a perfusion balloon catheter after abrupt coronary occlusion during coronary angioplasty solved the problems of acute myocardial ischemia and markedly lowered the definite myocardial infarction rate. This technique ensures favourable haemodynamic conditions for emergency myocardial revascularization. PMID:9201117

  11. Acute appendicitis mimicking intestinal obstruction in a patient with cystic fibrosis.

    PubMed

    Chen, Chun-Han; Chang, Cheng-Chih; Yang, Bor-Yau; Lin, Paul Y; Wang, Chia-Siu

    2012-10-01

    Cystic fibrosis (CF) is an inherited disease of the secretory glands caused by mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. The clinical manifestations of CF are repetitive lung infections, biliary cirrhosis, pancreatic abnormalities, and gastrointestinal disorders. We report a 21-year-old Taiwanese man with CF who had abdominal pain for 2 days. The diagnosis of CF had been confirmed by peripheral blood analysis of the CFTR gene 5 years before admission. He presented to the emergency department with nausea, vomiting, abdominal distension, and crampy abdominal pain, which is atypical for acute appendicitis. The physical examination and a series of studies revealed intestinal obstruction, but acute appendicitis could not be ruled out. After conservative treatment, together with empiric antibiotics, the refractory abdominal pain and leukocytosis with a left-shift warranted surgical intervention. A diagnostic laparoscopy revealed a swollen, hyperemic appendix, a severely distended small intestine, and serous ascites. The laparoscopic procedure was converted to a laparotomy for open disimpaction and appendectomy. He was discharged on the eighth postoperative day. The histologic examination of the appendix was consistent with early appendicitis. In conclusion, acute abdominal pain in adult CF patients is often associated with intestinal obstruction syndrome. The presentation of concurrent appendicitis may be indolent and lead not only to diagnostic difficulties, but also a number of therapeutic choices.

  12. Acute Intestinal Obstruction Complicating Abdominal Pregnancy: Conservative Management and Successful Outcome

    PubMed Central

    Udigwe, Gerald Okanandu; Ihekwoaba, Eric Chukwudi; Udegbunam, Onyebuchi Izuchukwu; Egeonu, Richard Obinwanne; Okwuosa, Ayodele Obianuju

    2016-01-01

    Background. Acute intestinal obstruction during pregnancy is a very challenging and unusual nonobstetric surgical entity often linked with considerable fetomaternal morbidity and mortality. When it is synchronous with abdominal pregnancy, it is even rarer. Case Presentation. A 28-year-old lady in her second pregnancy was referred to Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria, at 27 weeks of gestation due to vomiting, constipation, and abdominal pain. Examination and ultrasound scan revealed a single live intra-abdominal extrauterine fetus. Plain abdominal X-ray was diagnostic of intestinal obstruction. Conservative treatment was successful till the 34-week gestational age when she had exploratory laparotomy. At surgery, the amniotic sac was intact and the placenta was found to be adherent to the gut. There was also a live female baby with birth weight of 2.3 kg and Apgar scores of 9 and 10 in the 1st and 5th minutes, respectively, with the baby having right clubbed foot. Adhesiolysis and right adnexectomy were done. The mother and her baby were well and were discharged home nine days postoperatively. Conclusion. To the best of our knowledge, this is the first report of abdominal pregnancy as the cause of acute intestinal obstruction in the published literature. Management approach is multidisciplinary. PMID:27313923

  13. [Estimation of efficiency of complex-method intestinal therapy using Nitella flexilis test-object for acute intestinal obstruction of various etiology].

    PubMed

    Berishvili, K L; Rummo, O O; Kirkovskiĭ, V V; Tret'iak, S I; Korotkov, S V

    2005-12-01

    The aim of our investigation was to define the presence of correlation between toxicity of intestinal contents and clinical and laboratory indices in the cases of ileus and peritonitis with the use of complex method of enteral therapy. Experiments have been carried out on internodal cells of Nitella Flexilis water plant. Efficiency of the given method (investigation of toxicity of the intestinal content with the use of test-object Nitella Flexilis) has been studied in 25 patients, who underwent correction of morpho-functional status of small intestine. Results of investigation have shown that changes in toxicity of intestinal content reliably reflect the nature and dynamics of the pathobiologic processes proceeding in GIS in treated patients suffering from acute intestinal impassability. Using the method of correction of morpho-functional status of small intestine decreases the role of "Intestinal factor" in formation of endogenous intoxication, which in turn results in early normalization of clinical and laboratory indices, favored process of early post-operational period, decreased rate of lethality and shortened rehabilitation period.

  14. Acute Small Bowel Obstruction and Small Bowel Perforation as a Clinical Debut of Intestinal Endometriosis: A Report of Four Cases and Review of the Literature.

    PubMed

    Torralba-Morón, Angel; Urbanowicz, Maria; Ibarrola-De Andres, Carolina; Lopez-Alonso, Guadalupe; Colina-Ruizdelgado, Francisco; Guerra-Vales, Juan-Manuel

    2016-01-01

    Endometriosis is a quite common pathology, however, intestinal endometriosis is a rare condition, which typically occurs with chronic symptoms. Its acute presentation is very infrequent. We herein report four cases of intestinal endometriosis, in which the clinical debut occurred acutely: two as an acute small bowel obstruction and two as a small bowel perforation. None of the cases had a preoperative diagnosis of endometriosis. The interest of these cases lies in this exceptional form of presentation, such as a surgical acute abdomen. Therefore, intestinal endometriosis should be taken into account in the differential diagnosis of an acute obstructive or perforative process of the small or large bowel. PMID:27629952

  15. [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. PMID:26999860

  16. [Acute intestinal occlusion caused by phytobezoar in Israel. Role of oranges and persimmons].

    PubMed

    Serour, F; Dona, G; Kaufman, M; Weisberg, D; Krispin, M

    1985-05-01

    Forty-one patients were operated upon for acute intestinal obstruction secondary to the presence of phytobezoars, 34 of these patients (83%) having a history of previous gastric surgery for ulcer. The etiologic factor in 44% of cases was oranges and in 56% persimmons (Kakis). Treatment was by enterotomy in 27 patients (65,85%) and by "milking" in 14 (34,15%). Postoperative mortality was 2,44% (1 case). Recurrence was noted in three cases (7,3%) including one with an ileocutaneous fistula, treatment being by enterotomy in 2 cases and "milking" in the third patient. First intention intestinal resection was never required. Five patients required several admissions for subacute obstruction treated conservatively. These findings suggest that gastric surgery predisposes to intestinal obstruction by phytobezoar. Careful exploration of the digestive tube and particularly the stomach should avoid postoperative relapse, while prevention depends on a dietary regimen avoiding excessive intake of foods rich in cellulose, particularly oranges and persimmon fruit. PMID:4044688

  17. 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

  18. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

  19. Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells

    PubMed Central

    ZHENG, KAI; WU, WEIZHEN; YANG, SHUNLIANG; HUANG, LIANGHU; CHEN, JIN; GONG, CHUNGUI; FU, ZHICHAO; LIN, RUOFEI; TAN, JIANMING

    2016-01-01

    The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent. PMID:27284330

  20. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    PubMed

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  1. Acute lupus pneumonitis followed by intestinal pseudo-obstruction in systemic lupus erythematosus: A case report

    PubMed Central

    JI, CAIHONG; YU, XING; WANG, YONG; SHI, LUFENG

    2016-01-01

    Intestinal pseudo-obstruction (IpsO) and acute lupus pneumonitis (ALP) are uncommon severe complications of systemic lupus erythematosus (SLE). The present study reports the case of a 26-year-old female who presented with abdominal pain, nausea and vomiting as initial symptoms. Computed tomography (CT) scanning revealed the jejunal wall was thickened and streaky, mimicking the presentation of intestinal obstruction. Following emergency surgery, the patient's general condition was aggravated, with evident limb erythematous rashes. A series of laboratory examinations revealed SLE, and combined with patient's medical history IpsO was diagnosed, with a disease Activity Index score of 10. During the therapeutic period, high fever, dyspnea and oxygen saturation (SaO2) reductions were detected, and CT scans indicated lung infiltration, excluding other causes through a comprehensive infectious work-up and a bronchoalveolar lavage examination. ALP was confirmed and treated with high-dose methylprednisolone and gamma globulin supplement. The patient responded well and was discharged in 2 weeks. In the one-year tapering period and after stopping corticosteroids, the patient recovered well with no relapse detected. In conclusion, the manifestation of IpsO in SLE is rare and represents a challenge for the surgeon to establish the correct diagnosis and avoid inappropriate surgical intervention. ALP may be the consequence of emergency surgery, and immediate high-dose glucocorticoid therapy is recommended. PMID:27347044

  2. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis

    PubMed Central

    Hainzl, Eva; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit

    2015-01-01

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. PMID:26432894

  3. Surgical indicators for the operative treatment of acute mechanical intestinal obstruction due to adhesions

    PubMed Central

    Boluk, Salih; Bayraktar, Baris; Ozemir, Ibrahim Ali; Yildirim Boluk, Sumeyra; Tombalak, Ercument; Alimoglu, Orhan

    2015-01-01

    Purpose Our aim was to investigate the predictive factors indicating strangulation, and the requirement for surgery in patients with acute mechanical intestinal obstruction due to adhesions. Methods This study retrospectively evaluated the records of patients with adhesive acute mechanical intestinal obstruction. The surgical treatment (group S), conservative treatment (group C), intraoperative bowel ischemia (group I), and intraoperative adhesion only (group A) groups were statistically evaluated according to the diagnostic and surgical parameters. Results The study group of 252 patients consisted of 113 women (44.8%), and 139 men (55.2%). The mean age was 62.79 ± 18.08 years (range, 20-98 years). Group S consisted of 50 patients (19.8%), and 202 (80.2%) were in group C. Group I consisted of 19 patients (38%), where as 31 (62%) were in group A. In group S, the prehospital symptomatic period was longer, incidence of fever was increased, and elevated CRP levels were significant (P < 0.05). Plain abdominal radiography, and abdominal computerized tomography were significantly sensitive for strangulation (P < 0.05). The elderly were more prone to strangulation (P < 0.05). Fever, rebound tendernes, and urea & creatinine levels were significantly higher in the presence of strangulation (P < 0.05, P < 0.05, and P < 0.05, consecutively). Conclusion Fever, rebound tenderness, urea & creatinine levels, plain abdominal radiography, and abdominal computerized tomography images were important indicators of bowel ischemia. Longer prehospital symptomatic period was related with a tendency for surgical treatment, and the elderly were more prone to strangulation. CRP detection was considered to be useful for the decision of surgery, but not significantly predictive for strangulation. PMID:26029678

  4. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

    PubMed Central

    2009-01-01

    Background Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients. Methods One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT). Results Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO. Conclusion SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors. PMID:19643023

  5. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy.

    PubMed

    Kozuch, P L; Brandt, L J

    2005-02-01

    Mesenteric ischaemia results from decreased blood flow to the bowel, causing cellular injury from lack of oxygen and nutrients. Acute mesenteric ischaemia (AMI) is an uncommon disorder with high morbidity and mortality, but outcomes are improved with prompt recognition and aggressive treatment. Five subgroups of AMI have been identified, with superior mesenteric artery embolism (SMAE) the most common. Older age and cardiovascular disease are common risk factors for AMI, excepting acute mesenteric venous thrombosis (AMVT), which affects younger patients with hypercoaguable states. AMI is characterized by sudden onset of abdominal pain; a benign abdominal exam may be observed prior to bowel infarction. Conventional angiography and more recently, computed tomography angiography, are the cornerstones of diagnosis. Correction of predisposing conditions, volume resuscitation and antibiotic treatment are standard treatments for AMI, and surgery is mandated in the setting of peritoneal signs. Intra-arterial vasodilators are used routinely in the treatment of non-occlusive mesenteric ischaemia (NOMI) and also are advocated in the treatment of occlusive AMI to decrease associated vasospasm. Thrombolytics have been used on a limited basis to treat occlusive AMI. A variety of agents have been studied in animal models to treat reperfusion injury, which sometimes can be more harmful than ischaemic injury. Chronic mesenteric ischaemia (CMI) usually is caused by severe obstructive atherosclerotic disease of two or more splanchnic vessels, presents with post-prandial pain and weight loss, and is treated by either surgical revascularization or percutaneous angioplasty and stenting.

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

    PubMed

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

    2016-02-15

    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.

  7. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Kim, Yeon Joo; Park, Jin-hong; Yun, In-Ha; Kim, Young Seok

    2016-01-01

    Purpose To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. PMID:27022287

  8. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

    PubMed

    Vreugdenhil, A C; Dentener, M A; Snoek, A M; Greve, J W; Buurman, W A

    1999-09-01

    The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.

  9. [Primary volvulus of the small intestine: vascular-like acute abdomen].

    PubMed

    Damiani, S; Ruscazio, M; Ciulla, A; Miceli, G; Tomasello, G

    1998-01-01

    The Authors discuss etiology, clinical picture, diagnostic and therapeutic possibilities of intestinal volvulus, an uncommon disease in Europe, thinking of a case of primitive small intestine volvulus, recently observed, and considering the literature. The Authors have come to the conclusion that in all the cases of intestinal occlusion, in emergency hospitalization, it is important to suspect the intestinal volvulus and to operate on the patient urgently to avoid the raise of postoperative mortality in all the cases complicated with intestinal gangrene.

  10. Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets

    PubMed Central

    Jacobi, Sheila K; Moeser, Adam J; Blikslager, Anthony T; Rhoads, J Marc; Corl, Benjamin A; Harrell, Robert J; Odle, Jack

    2013-01-01

    AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. METHODS: Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses. RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). 3H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. CONCLUSION: Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model. PMID:23964143

  11. Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus

    PubMed Central

    2012-01-01

    Background Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer’s Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. Results Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer’s Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, while a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum) at 28 dpi. Conclusion Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only the virus-specific antibody response but also IgA responses to other pathogens and

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

    PubMed

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

    2015-07-08

    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.

  13. 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

  14. Intestinal Infarction Caused by Thrombophlebitis of the Portomesenteric Veins as a Complication of Acute Gangrenous Appendicitis After Appendectomy

    PubMed Central

    Tang, Rui; Tian, Xiaodong; Xie, Xuehai; Yang, Yinmo

    2015-01-01

    Abstract The clinical symptoms of pylephlebitis caused by acute appendicitis are varied and atypical, which leads to delayed diagnosis and poor outcomes. Here, we report a case of intestinal necrosis caused by thrombophlebitis of the portomesenteric veins as a complication of acute appendicitis after appendectomy. The patient had acute abdominal pain with tenderness and melena on the 3rd day after appendectomy for the treatment of gangrenous appendicitis. He was diagnosed with intestinal infarction caused by thrombophlebitis of the portomesenteric veins based on enhanced CT and diagnostic abdominal paracentesis. The patient was treated by bowel excision anastomosis and thrombectomy. After postoperative antibiotic and anticoagulation treatments, the patient recovered well and was discharged 22 days after the 2nd operation. A follow-up CT scan showed no recurrence of portomesenteric veins thrombosis 3 months later. Thrombophlebitis of the portomesenteric veins is a rare but fatal complication of acute appendicitis. For all the cases with acute abdominal pain, the possibility of thrombophlebitis should be considered as a differential diagnosis. Once pylephlebitis is suspected, enhanced CT scan is helpful for early diagnosis, and sufficient control of inflammation as well as anticoagulant therapy should be performed. PMID:26091450

  15. [Impact of lactic acid fermentation in the large intestine on acute lactic acidosis in cattle].

    PubMed

    Zust, J; Pestevsek, U; Vengust, A

    2000-09-01

    Microbial and fermentation changes in the ingesta of the large intestine and their influence on the pathogenesis of acute lactic acidosis were studied in 4 cows fitted with permanent cannulas in the ileum and cecum. Feed mixture containing 65% of maize was infused into the cecum for several days in amounts of 2 and 4 kg per day. The daily amount was divided in 8 equal portions and given with 3 l of warm physiologic saline solution. During the period of ad libitum feeding of hay, the pH values in cecal digesta were 7.4 to 7.6 and the amount of total volatile fatty acids 40-60 mmol/kg with high molar percentage (87-90 mol%) of acetic acid. As to lactic acid only the L(+) lactic isomer was found in a concentration of about 0.4 mmol/kg. Infusion of low amounts of starch induced mild lactic acid fermentation in the cecum associated with a pronounced increase in the concentration of L(+) and D (-) lactic acid to peak levels of 80 +/- 10 mmol/kg and 7 +/- 1 mmol/kg, respectively. Lactic acid fermentation ceased within 2 to 3 days indicating that the gut microflora had adapted to the starch infusion. Slight decreases of blood pH and bicarbonates in blood as well as a moderate increase of netto acid-base excretion in urine indicated mild changes of acid-base balance, but clinically no pathological symptoms were observed. Higher amounts of infused starch caused pronounced lactic acid production in the large intestine which persisted throughout the experiment. Peak L(+) and D(-) lactic acid concentration in cecal digesta reached on the average 137 +/- 16 mmol/kg and 45 +/- 7 mmol/kg respectively. Significant decreases of blood pH values from 7.41 +/- 0.02 to 7.18 +/- 0.08 (P < 0.001), actual bicarbonate from 28.2 +/- 3.2 to 11.0 +/- 2.6 mmol/l (P < 0.001) and base excess from 3.9 +/- 3.6 to -15.2 +/- 3.8 mmol/l (P < 0.001) were observed. D (-) lactic acid concentration in blood increased to 3.2 +/- 0.4 mmol/l, but L(+) lactic acid values remained unchanged under 1 mmol

  16. A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab.

    PubMed

    Rao, B; Jafri, S-M; Kazimi, M; Mullins, K; Raoufi, M; Segovia, M C

    2016-03-01

    There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

  17. Hydroclimatic variables and acute gastro-intestinal illness in British Columbia, Canada: A time series analysis

    NASA Astrophysics Data System (ADS)

    Galway, L. P.; Allen, D. M.; Parkes, M. W.; Li, L.; Takaro, T. K.

    2015-02-01

    Using epidemiologic time series analysis, we examine associations between three hydroclimatic variables (temperature, precipitation, and streamflow) and waterborne acute gastro-intestinal illness (AGI) in two communities in the province of British Columbia (BC), Canada. The communities were selected to represent the major hydroclimatic regimes that characterize BC: rainfall-dominated and snowfall dominated. Our results show that the number of monthly cases of AGI increased with increasing temperature, precipitation, and streamflow in the same month in the context of a rainfall-dominated regime, and with increasing streamflow in the previous month in the context of a snowfall-dominated regime. These results suggest that hydroclimatology plays a role in driving the occurrence and variability of AGI in these settings. Further, this study highlights that the nature and magnitude of the effects of hydroclimatic variability on AGI are different in the context of a snowfall-dominated regime versus a rainfall-dominated regimes. We conclude by proposing that the watershed may be an appropriate context for enhancing our understanding of the complex linkages between hydroclimatic variability and waterborne illness in the context of a changing climate.

  18. Berberine ameliorates severe acute pancreatitis‑induced intestinal barrier dysfunction via a myosin light chain phosphorylation‑dependent pathway.

    PubMed

    Liang, Hong-Yin; Chen, Tao; Yan, Hong-Tao; Huang, Zhu; Tang, Li-Jun

    2014-05-01

    Berberine is a traditional drug used to treat gastrointestinal disorders in China and has been demonstrated to attenuate intestinal barrier dysfunction in certain animal models. However, the effects of berberine on pancreatitis-induced intestinal barrier dysfunction are yet to be fully elucidated. This study aimed to investigate the effect of berberine pretreatment on the attenuation of intestinal barrier dysfunction induced by severe acute pancreatitis (SAP). A total of 36 rats were randomly divided into Sham, SAP and SAP plus berberine groups. Pancreatitis was induced using retrograde injection of 3% Na-taurocholate into the pancreatic duct. Histological examinations of the pancreas were performed and intestinal barrier dysfunction was characterized by histological measurements and the assessment of serum diamine oxidase activity and endotoxin levels. Zonula occludens-1 and occludin mRNA and protein expression, as well as myosin light chain (MLC) phosphorylation, were assessed. SAP rat models were successfully established. Berberine treatment was found to have no significant effect on the histological changes in the pancreas, but was observed to ameliorate the intestinal mucosal barrier damage and membrane permeability associated with SAP. Although berberine exerted minimal effects on tight junction proteins in the ilea of SAP rats, it was observed to significantly inhibit SAP-induced MLC phosphorylation. To the best of our knowledge, this is the first study to demonstrate that berberine attenuates SAP‑induced intestinal barrier dysfunction in vivo. In addition, this study shows that the effect of berberine on intestinal barrier function may be associated with the inhibition of SAP‑induced upregulation of MLC phosphorylation.

  19. Ischaemia-induced cellular electrical uncoupling and ventricular fibrillation

    PubMed Central

    de Groot, J.R.

    2002-01-01

    Sudden death resulting from ventricular fibrillation (VF) during acute myocardial ischaemia forms an important contribution to mortality associated with infarction. Its temporal distribution is not known, but 30% of mortality occurs within the first 60 minutes. Two distinct phases of arrhythmias have been demonstrated in laboratory animals subjected to coronary occlusion. The mechanism of the second, 1B phase (which is associated with more lethal events than the first, 1A phase) is largely unknown but appears to be related to cellular uncoupling, i.e. the closure of gap junctions. Gap junctions are intercellular communication channels that are permeable for ions and metabolites and are necessary for normal propagation of electrical activation. It has been suggested that closure of gap junctions results in a largely inhomogeneous substrate in which microreentry forms the electrophysiological mechanism for VF. However, there is growing support for the hypothesis that arrhythmias relate to the persistence of residual coupling rather than to the occurrence of uncoupling. With this, the ischaemic midmyocardium can depress the intrinsically viable tissue of the ischaemic subepicardium and subendocardium and cause conduction slowing and block leading to arrhythmias. Progression of uncoupling terminates this interaction and allows the subepicardium and subendocardium to recover. Indeed, electrophysiological properties recover subepicardially whereas the midmyocardial tissue becomes inexcitable. In addition, activation patterns during VF become restricted to the two-dimensional plane of the subepicardium. These observations support the hypothesis of residual coupling as an arrhythmogenic mechanism during the delayed phase of acute ischaemia. Whether this mechanism is equally important in patients with remodelled and failing hearts can at this time only be speculated upon. However, modifying intercellular coupling might turn out a new antiarrhythmic therapy. ImagesFigure 1

  20. Apical leptin induces chloride secretion by intestinal epithelial cells and in a rat model of acute chemotherapy-induced colitis

    PubMed Central

    Hoda, Raschid M.; Scharl, Michael; Keely, Stephen J.; McCole, Declan F.

    2010-01-01

    The purpose of this study was to investigate whether luminal leptin alters ion transport properties of the intestinal epithelium under acute inflammatory conditions. Monolayers of human intestinal T84 epithelial cells and a rat model of chemotherapy-induced enterocolitis were used. Cells were treated with leptin and mounted in Ussing chambers to measure basal and secretagogue-induced changes in transepithelial short-circuit current (Isc). Furthermore, the role of MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating responses to leptin was investigated. Acute colitis in Sprague-Dawley rats was induced by intraperitoneal injection of 40 mg/kg methotrexate. Leptin (100 ng/ml) induced a time-dependent increase in basal Isc in T84 intestinal epithelial cells (P < 0.01). Moreover, pretreatment of T84 cells with leptin for up to 1 h significantly potentiated carbachol- and forskolin-induced increases in Isc. Pretreatment with an inhibitor of MAPK abolished the effect of leptin on basal, carbachol- and forskolin-induced chloride secretion (P < 0.05). However, the PI3K inhibitor, wortmannin, only blunted the effect of leptin on forskolin-induced increases in Isc. Furthermore, leptin treatment evoked both ERK1/2 and Akt1 phosphorylation in T84 cells. In the rat model, luminal leptin induced significant increases in Isc across segments of proximal and, to a lesser extent, distal colon (P < 0.05). We conclude that luminal leptin is likely an intestinal chloride secretagogue, particularly when present at elevated concentrations and/or in the setting of inflammation. Our findings may provide a mechanistic explanation, at least in part, for the clinical condition of secretory diarrhea both in hyperleptinemic obese patients and in patients with chemotherapy-induced intestinal inflammation. PMID:20203064

  1. Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: a case report with review of literature.

    PubMed

    Afroz, Nishat; Shamim, Nida; Sofi, Lateef Ahmed; Rizvi, Syed Amjad Ali

    2014-01-01

    Goblet cell carcinoid (GCC) is a rare variant of carcinoid tumor that exclusively involves the appendix. It usually occurs in 5th-6th decade with the most common clinical presentation being acute appendicitis. The natural history of this tumor is intermediate between carcinoids and adenocarcinomas. We here report a case of GCC diagnosed incidentally in a patient presenting with acute intestinal obstruction. Ultrasonographic examination supported the clinical diagnosis of acute intestinal obstruction, following which the patient underwent laparotomy and resection of ileum along with appendix was done. On gross pathological examination, a nodular growth was present on the tip and body of appendix that was yellow in color with a semi-solid to mucoid consistency on cut section. On microscopy, lakes of mucin with few acinar structures floating in them were seen. The submucosa as well as serosa were infiltrated by clusters of goblet cells and well-formed acini, with little atypia. Glands and nests were positive for periodic acid Schiff and immunohistochemistry showed focal chromogranin positivity in glandular structures, thereby confirming the diagnosis of GCC. Although the prognosis of GCC is better than adenocarcinomas, it is one of the carcinoids having a poorer outcome when compared with other variants of carcinoid tumor. Therefore, it is important to rule out other differential diagnoses of goblet cell carcinoid, the most important being mucinous adenocarcinomas. PMID:24739849

  2. Resistin worsens cardiac ischaemia-reperfusion injury.

    PubMed

    Rothwell, Sarah E; Richards, A Mark; Pemberton, Christopher J

    2006-10-13

    We provide the first report of direct effects of resistin upon haemodynamic and neurohumoral parameters in isolated perfused rat heart preparations. Pre-conditioning with 1 nmol L-1 recombinant human resistin prior to ischaemia significantly impaired contractile recovery during reperfusion, compared with vehicle-infused hearts (P<0.05, n=12). This was accompanied by a significant increase in both A-type and B-type natriuretic peptides (P<0.05, n=12 both ANP and BNP vs vehicle), creatine kinase, and tumour necrosis factor-alpha (TNF-alpha) release in resistin-infused hearts. Resistin had no significant effect on myocardial glucose uptake. Co-infusion of resistin with Bay 11 7082 (an NF-kappaB inhibitor) improved contractile recovery following ischaemia and reduced both natriuretic peptide and creatine kinase release. This is the first evidence indicating resistin impairs cardiac recovery following ischaemia, stimulates cardiac TNF-alpha secretion, and modulates reperfusion release of natriuretic peptides and biochemical markers of myocardial damage. A TNF-alpha signalling related mechanism is suggested as one component underlying these effects.

  3. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  4. 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

  5. Cerebral ischaemia after repair of coarctation of the aorta.

    PubMed

    Gogou, Maria; Keivanidou, Anastasia; Giannopoulos, Andreas

    2015-04-01

    A 9-year-old boy, with a history of repair of severe coarctation of the aorta through balloon angioplasty 2 weeks ago, presented in the emergency paediatric department with symptoms consistent with transient cerebral ischaemia. MRI revealed an area of cerebral infarction in the right frontal lobe. Causes of cerebral ischaemia after aortic coarctation repair are briefly discussed.

  6. 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

    The effect of three dietary treatments on intestinal permeability during acute diarrhea was compared in 86 Tanzanian children 6-25 months of age admitted to Muhimbili Medical Center's Pediatric Diarrhea Treatment Unit in Dar es Salaam in 1992. 55 children (64%) had received foods other than breast milk during the first week of life. After rehydration, children were randomly assigned to receive a conventional low-energy density porridge (n = 33), a high-energy density amylase digested (AMD) porridge (n = 28), or AMD porridge followed by fermented amylase digested (FAD) porridge (n = 25). Lactulose/mannitol (L/M) permeability tests were performed at admission, after 3 days, and at 2 and 4 weeks after hospital discharge. Children with diarrhea had higher L/M ratios (geometric mean, 0.85; 95% confidence interval (CI), 0.68-1.05) at admission than the 30 age-matched healthy controls (mean, 0.14; 95% CI, 0.12-0.17). The L/M ratio of study children fell over time and approached values recorded among healthy controls by the first follow-up visit. The change in L/M ratio between admission and day 3 of hospitalization was significantly greater in the FAD group (89%) than the conventional or AMD groups (44% and 75%, respectively). Dietary treatment and intestinal damage at admission explained 13.5% of the variation in this L/M ratio, while age at admission and age at weaning explained an additional 8.4%. These findings suggest that a porridge that has been both amylase digested and fermented effectively repairs mucosal damage through trophic effects on intestinal epithelium and should be administered to children with acute diarrhea to prevent malnutrition.

  7. Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

    PubMed Central

    Sun, Xiaofeng; Cárdenas, Andrés; Wu, Yan; Enjyoji, Keichi; Robson, Simon C.

    2009-01-01

    Vasoactive factors that regulate splanchnic hemodynamics include nitric oxide, catecholamines, and possibly extracellular nucleosides/nucleotides (adenosine, ATP). CD39/ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1) is the major vascular ectonucleotidase that hydrolyzes extracellular nucleotides. CD39 activity may be modulated by vascular injury, inflammation, and altered oxygen tension. Altered Cd39 expression by the murine hepatosplanchnic vasculature may impact hemodynamics and portal hypertension (PHT) in vivo. We noted that basal portal pressures (PPs) were comparable in wild-type and Cd39-null mice (n = 9). ATP infusions resulted in increments in PP in wild-type mice, but, in contrast, this significantly decreased in Cd39-null mice (n = 9) post-ATP in a nitric oxide-dependent manner. We then studied Cd39/NTPDase1 deletion in the regulation of portal hemodynamics, vascular integrity, and intestinal permeability in a murine model of PHT. Partial portal vein ligation (PPVL) was performed in Cd39-null (n = 44) and wild-type (n = 23) mice. Sequential measurements obtained after PPVL were indicative of comparable levels of PHT (ranges 14–29 mmHg) in both groups. There was one death in the wild-type group and eight in the Cd39-null group from intestinal bleeding (P = 0.024). Circulatory stasis in the absence of overt portal vein thrombosis, portal congestion, intestinal hemorrhage, and increased permeability were evident in all surviving Cd39-null mice. Deletion of Cd39 results in deleterious outcomes post-PPVL that are associated with significant microcirculatory derangements and major intestinal congestion with hemorrhage mimicking acute mesenteric occlusion. Absent Cd39/NTPDase1 and decreased generation of adenosine in the splanchnic circulation cause heightened vascular permeability and gastrointestinal hemorrhage in PPVL. PMID:19520738

  8. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation

    PubMed Central

    Pearson, Claire; Thornton, Emily E; McKenzie, Brent; Schaupp, Anna-Lena; Huskens, Nicky; Griseri, Thibault; West, Nathaniel; Tung, Sim; Seddon, Benedict P; Uhlig, Holm H; Powrie, Fiona

    2016-01-01

    Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response. DOI: http://dx.doi.org/10.7554/eLife.10066.001 PMID:26780670

  9. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation.

    PubMed

    Pearson, Claire; Thornton, Emily E; McKenzie, Brent; Schaupp, Anna-Lena; Huskens, Nicky; Griseri, Thibault; West, Nathaniel; Tung, Sim; Seddon, Benedict P; Uhlig, Holm H; Powrie, Fiona

    2016-01-01

    Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response. PMID:26780670

  10. 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

  11. 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

  12. [The redox potentials and morphological features of the pancreas, small intestines and liver under early enteral nutrition via micro-jejunostomy in modeling of acute pancreatitis].

    PubMed

    Khatchapuridze, G; Leonov, V

    2014-01-01

    The article investigates morphological changes in pancreas, liver, and small intestine after early enteral nutrition in Vistar rats after modeling of acute pancreatitis and creation of jejunostomy. Morphological changes and redox potential measurements show that early enteral nutrition via micro-jejunostomy slows down the development of pathological processes in Vistar rats. PMID:24523337

  13. 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.

  14. 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.

  15. Intestinal transplantation: living related.

    PubMed

    Pollard, S G

    1997-01-01

    The use of live donors in intestinal transplantation could potentially both reduce the severity of rejection responses against this highly immunogenic organ by better tissue matching and also reduce cold ischaemia times. These two advantages over cadaveric grafts could preserve mucosal integrity and reduce the risk of systemic sepsis from bacterial translocation. The disadvantages of live donation are the inherent risk to the donor and the compromise of using a shorter graft. Although only a handful of such cases have been performed, the success rate has been high and this is a therapeutic modality which should be explored further. PMID:9536535

  16. Acute Heat Stress and Reduced Nutrient Intake Alter Intestinal Proteomic Profile and Gene Expression in Pigs

    PubMed Central

    Pearce, Sarah C.; Lonergan, Steven M.; Huff-Lonergan, Elisabeth; Baumgard, Lance H.; Gabler, Nicholas K.

    2015-01-01

    Heat stress and reduced feed intake negatively affect intestinal integrity and barrier function. Our objective was to compare ileum protein profiles of pigs subjected to 12 hours of HS, thermal neutral ad libitum feed intake, or pair-fed to heat stress feed intake under thermal neutral conditions (pair-fed thermal neutral). 2D-Differential In Gel Electrophoresis and gene expression were performed. Relative abundance of 281 and 138 spots differed due to heat stress, compared to thermal neutral and pair-fed thermal neutral pigs, respectively. However, only 20 proteins were different due to feed intake (thermal neutral versus pair-fed thermal neutral). Heat stress increased mRNA expression of heat shock proteins and protein abundance of heat shock proteins 27, 70, 90-α and β were also increased. Heat stress reduced ileum abundance of several metabolic enzymes, many of which are involved in the glycolytic or TCA pathways, indicating a change in metabolic priorities. Stress response enzymes peroxiredoxin-1 and peptidyl-prolyl cis-trans isomerase A were decreased in pair-fed thermal neutral and thermal neutral pigs compared to heat stress. Heat stress increased mRNA abundance markers of ileum hypoxia. Altogether, these data show that heat stress directly alters intestinal protein and mRNA profiles largely independent of reduced feed intake. These changes may be related to the reduced intestinal integrity associated with heat stress. PMID:26575181

  17. 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

  18. Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia.

    PubMed

    Maranta, F; Tondi, L; Agricola, E; Margonato, A; Rimoldi, O; Camici, Paolo G

    2015-11-01

    Ivabradine is an effective treatment for angina in patients with stable coronary artery disease (CAD) and for heart failure. Experiments in a canine model have shown that ivabradine reduces both acute left ventricular (LV) dysfunction and post-ischaemic stunning. Aim of this study was to investigate the effect of ivabradine on LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. Fifteen patients with ejection fraction >40 % and heart rate >70 bpm were enrolled. After pharmacologic washout, echocardiography was performed at rest, at peak treadmill exercise and during recovery until return to baseline. After 2 weeks of ivabradine (7.5 mg bid) stress echocardiography was repeated at the same workload achieved during washout. Peak global and segmental (ischaemic vs. remote normal segments) LV longitudinal strain (LS) was assessed by 2D speckle tracking analysis. At washout, LS was significantly impaired in ischaemic compared to remote segments at peak stress and for several minutes during recovery. After ivabradine a smaller, albeit still significant, impairment of LS in ischaemic segments was observed at peak whilst no difference with remote segments was present during recovery. Furthermore, the average global LS value improved significantly after treatment. In conclusion, ivabradine reduces both acute LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. We hypothesise that this mechanism might contribute to reduce chronic LV dysfunction in patients with CAD. In this setting the drug might limit the development of hibernating myocardium which is believed to result from repeated episodes of ischaemia and stunning. PMID:26419678

  19. Superior mesenteric arteriovenous fistula embolisation complicated by bowel ischaemia

    PubMed Central

    Hussein, Maher; Issa, Ghada; Muhsen, Shirin; Haydar, Ali

    2013-01-01

    Superior mesenteric arteriovenous fistulas are rare, especially when iatrogenic in origin. Management of these fistulas can be surgical or endovascular. Endovascular embolisation is the preferred modality with a low rate of complications. Among the reported complications, bowel ischaemia is considered an unlikely occurrence. We report a case of a complex iatrogenic arterioportal fistula that was managed by endovascular embolisation and controlled through both its inflow and outflow, and was later complicated by bowel ischaemia. PMID:23682091

  20. 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.

  1. 9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection.

    PubMed

    Bell, R M; Bøtker, H E; Carr, R D; Davidson, S M; Downey, J M; Dutka, D P; Heusch, G; Ibanez, B; Macallister, R; Stoppe, C; Ovize, M; Redington, A; Walker, J M; Yellon, D M

    2016-07-01

    In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man. PMID:27164905

  2. Impact of acute water and feed deprivation events on growth performance, intestinal characteristics, and serum stress markers in weaned pigs.

    PubMed

    Horn, N; Ruch, F; Miller, G; Ajuwon, K M; Adeola, O

    2014-10-01

    The impact of acute stressors (24-h feed or water deprivation) on growth performance, intestinal characteristics, and serum stress markers in weaned pigs was evaluated. Pigs (6.21 ± 0.29 kg) were allotted in a randomized complete block design to 4 treatments on the basis of BW at the time of weaning. There were 8 mixed-sex pigs in each of 12 pens per treatment. Treatments were arranged as a 2 × 2 factorial and consisted of a feed or water stressor that included a 0- or 24-h deprivation period postweaning, and pigs were subsequently allowed access to feed and water. Growth performance was measured 1, 7, 14, and 28 d postweaning. Serum and intestinal samples were taken 1 and 7 d postweaning. Serum was analyzed for cortisol and corticotrophin-releasing factor, and villus height, crypt depth, and mast cell density were measured in the jejunum and the ileum. Expression of mucin (MUC2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1) genes were measured on d 1 and 7 postweaning in the jejunum and ileum by real-time PCR. There was a decrease (P < 0.05) in ADG with the water stressor 1 d postweaning, although subsequently, there were improvements (P < 0.05) in ADG and feed efficiency. Furthermore, the water stressor reduced ADFI during the last 14 d of the trial and cumulatively (P < 0.05). Seven days postweaning there was an increase (P < 0.05) in jejunal villous height to depth ratio due to the feed stressor and a decrease (P < 0.05) in the ileal villous height to depth ratio due to the water stressor. There was an increase (P < 0.05) in serum cortisol levels due to the water stressor both 1 and 7 d postweaning. Furthermore, there was an increase in serum corticotrophin-releasing factor 1 d but not 7 d postweaning due to the water stressor (P < 0.05). The feed stressor reduced (P < 0.05) TNF-α gene expression, and the water stressor reduced (P < 0.05) OC gene expression in the jejunum 1 d

  3. 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

  4. Lifesaving Treatment of Acute Stanford B Aortic Dissection Complicated by Intestinal Ischemia with Stent Placement in the Superior Mesenteric Artery: A Case Report

    PubMed Central

    Itagaki, Ryo; Arao, Kenshiro; Makita, Kouzou

    2016-01-01

    A 44-year-old man was transported to our hospital with chief complaints of back pain and paralysis of the leg. Contrast-enhanced computed tomography (CT) imaging revealed an acute Stanford B aortic dissection (AD), which was complicated by acute arterial occlusion of the left external iliac artery. The patient was treated by femorofemoral crossover bypass. Thereafter, abdominal pain was noted, and the patient was diagnosed with intestinal ischemia due to occlusion of the celiac artery and superior mesenteric artery (SMA). A stent was emergently placed into SMA. Subsequently, the patient demonstrated good postoperative progress and was discharged on hospital day 27. PMID:27738474

  5. Intestinal Infarction Caused by Thrombophlebitis of the Portomesenteric Veins as a Complication of Acute Gangrenous Appendicitis After Appendectomy: A Case Report.

    PubMed

    Tang, Rui; Tian, Xiaodong; Xie, Xuehai; Yang, Yinmo

    2015-06-01

    The clinical symptoms of pylephlebitis caused by acute appendicitis are varied and atypical, which leads to delayed diagnosis and poor outcomes. Here, we report a case of intestinal necrosis caused by thrombophlebitis of the portomesenteric veins as a complication of acute appendicitis after appendectomy. The patient had acute abdominal pain with tenderness and melena on the 3rd day after appendectomy for the treatment of gangrenous appendicitis. He was diagnosed with intestinal infarction caused by thrombophlebitis of the portomesenteric veins based on enhanced CT and diagnostic abdominal paracentesis. The patient was treated by bowel excision anastomosis and thrombectomy. After postoperative antibiotic and anticoagulation treatments, the patient recovered well and was discharged 22 days after the 2nd operation. A follow-up CT scan showed no recurrence of portomesenteric veins thrombosis 3 months later. Thrombophlebitis of the portomesenteric veins is a rare but fatal complication of acute appendicitis. For all the cases with acute abdominal pain, the possibility of thrombophlebitis should be considered as a differential diagnosis. Once pylephlebitis is suspected, enhanced CT scan is helpful for early diagnosis, and sufficient control of inflammation as well as anticoagulant therapy should be performed.

  6. Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

    PubMed

    Noth, Rainer; Häsler, Robert; Stüber, Eckhard; Ellrichmann, Mark; Schäfer, Heiner; Geismann, Claudia; Hampe, Jochen; Bewig, Burkhard; Wedel, Thilo; Böttner, Martina; Schreiber, Stefan; Rosenstiel, Philip; Arlt, Alexander

    2013-04-01

    Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

  7. Takotsubo cardiomyopathy with left ventricular thrombus presenting as critical limb ischaemia.

    PubMed

    Gulsin, Gaurav; Serna, Solange; Morris, Clare; Taher, Abutariq; Loke, Ian

    2016-08-01

    Takotsubo cardiomyopathy (TC) is a rare condition, characterized by acute left ventricular (LV) dysfunction in the absence of flow-limiting coronary artery disease, usually provoked by a physical or emotional stressor. The condition is far more common in women. The commonest presenting symptoms in patients with TC are chest pain and shortness of breath, often mimicking an acute coronary syndrome. A number of complications of TC are recognized, and very rarely patients experience cardioembolic phenomena secondary to LV thrombus formation in TC. We present the case of a 48-year-old lady presenting with peripheral limb ischaemia, subsequently found to have an LV thrombus secondary to TC. Diagnosis of TC was made challenging by the absence of chest pain. She required urgent arterial embolectomy and was treated with 6-month oral anticoagulation therapy. She was also commenced on beta-blocker and angiotensin-converting enzyme inhibitor treatment for the management of LV dysfunction. PMID:27679725

  8. Takotsubo cardiomyopathy with left ventricular thrombus presenting as critical limb ischaemia

    PubMed Central

    Gulsin, Gaurav; Serna, Solange; Morris, Clare; Taher, Abutariq; Loke, Ian

    2016-01-01

    Takotsubo cardiomyopathy (TC) is a rare condition, characterized by acute left ventricular (LV) dysfunction in the absence of flow-limiting coronary artery disease, usually provoked by a physical or emotional stressor. The condition is far more common in women. The commonest presenting symptoms in patients with TC are chest pain and shortness of breath, often mimicking an acute coronary syndrome. A number of complications of TC are recognized, and very rarely patients experience cardioembolic phenomena secondary to LV thrombus formation in TC. We present the case of a 48-year-old lady presenting with peripheral limb ischaemia, subsequently found to have an LV thrombus secondary to TC. Diagnosis of TC was made challenging by the absence of chest pain. She required urgent arterial embolectomy and was treated with 6-month oral anticoagulation therapy. She was also commenced on beta-blocker and angiotensin-converting enzyme inhibitor treatment for the management of LV dysfunction.

  9. Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells.

    PubMed

    Hashimoto, Akari; Sato, Tsutomu; Iyama, Satoshi; Yoshida, Masahiro; Ibata, Soushi; Tatekoshi, Ayumi; Kamihara, Yusuke; Horiguchi, Hiroto; Murase, Kazuyuki; Kawano, Yutaka; Takada, Kohichi; Miyanishi, Koji; Kobune, Masayoshi; Ichimiya, Shingo; Kato, Junji

    2016-01-01

    Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells.

  10. Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells

    PubMed Central

    Iyama, Satoshi; Yoshida, Masahiro; Ibata, Soushi; Tatekoshi, Ayumi; Kamihara, Yusuke; Horiguchi, Hiroto; Murase, Kazuyuki; Kawano, Yutaka; Takada, Kohichi; Miyanishi, Koji; Kobune, Masayoshi; Ichimiya, Shingo; Kato, Junji

    2016-01-01

    Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells. PMID:27031239

  11. Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection

    SciTech Connect

    Montufar-Solis, Dina; Garza, Tomas; Teng, B.-B.; Klein, John R. . E-mail: john.r.klein@uth.tmc.edu

    2006-04-14

    Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOS stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.

  12. Eosinophilic Gastroenteritis With Malabsorption, Acute Intestinal Obstruction, Ascites and Pleural Effusion: A Case Report and Review of Literature

    PubMed Central

    de Matos Brasil, Aloisio Antonio Gomes; Bezerra, Luiza Neves Pinheiro; Bruno, Estela Lucena Alcantara; Carvalho, Danyelle Rolim; de Oliveira, Paulo Levi Pereira; Leite, Roana Lacerda Tavares

    2013-01-01

    We report a case of a 49-year-old male patient with abdominal distension and diffuse stomach cramps associated with peripheral eosinophilia. Treatment for eosinophilic parasitosis was not effective. After a few weeks, the patient developed acute obstructive abdomen with ascites, which was atypically improved with the use of antispasmodics and analgesics. Upper digestive endoscopy, colonoscopy and histopathologic examination of the gastric and intestinal mucosa did not show any significant changes. Video laparoscopic biopsy of the mesenteric lymph node and peritoneum revealed a nonspecific chronic inflammatory process with intense diffuse tissue eosinophilia. Complementary tests revealed right-sided pleural effusion and increased serum immunoglobulin E levels, with altered D-xylose absorption test results. The patient was treated with a hypoallergenic diet and an oral corticosteroid; the symptoms resolved and the laboratory test results improved. Eosinophilic gastroenteritis is a rare inflammatory disease characterized by eosinophilic infiltration in the wall of the gastrointestinal tract. The clinical presentation varies according to the affected site and the depth and extent of digestive tract involvement. This case report, which presents the rare simultaneous involvement of the mucosal, muscular and serosal layers, aims to describe and discuss the clinical and therapeutic aspects of eosinophilic gastroenteritis as well as its progression.

  13. Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway

    PubMed Central

    Kundu, Parag; Ling, Teo Wei; Korecka, Agata; Li, Yinghui; D'Arienzo, Rossana; Bunte, Ralph M.; Berger, Thorsten; Arulampalam, Velmurugesan; Chambon, Pierre; Mak, Tak Wah; Wahli, Walter; Pettersson, Sven

    2014-01-01

    To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. PMID:24465207

  14. Repolarisation and refractoriness during early ischaemia in humans

    PubMed Central

    Sutton, P; Taggart, P; Opthof, T; Coronel, R; Trimlett, R; Pugsley, W; Kallis, P

    2000-01-01

    OBJECTIVES—To determine whether effective refractory period (ERP) shortens or lengthens in the first minutes of ischaemia in humans, and the relation between ERP changes and action potential duration (APD).
METHODS—ERP and monophasic action potential duration (MAPD) were measured from a single left ventricular epicardial site in 26 patients undergoing coronary artery surgery. Cardiopulmonary bypass was instituted and normothermia maintained. Refractory period was determined by the extrastimulus technique at a basic cycle length of 500 ms, at four times (group 1, 15 patients) or two times (group 2, 11 patients) the preischaemic diastolic threshold. A three minute period of ischaemia was instituted by aortic cross clamping between the input from the pump oxygenator and the heart.
RESULTS—After three minutes of ischaemia, mean (SEM) ERP lengthened from 232 (5) ms (control) to 246 (7) ms (p < 0.005) in group 1, and from 256 (10) ms (control) to 348 (25) ms (p < 0.005) in group 2. In the same time MAPD shortened from 256 (5) ms (control) to 189 (9) ms (p < 0.001) with no difference between groups. Thus postrepolarisation refractoriness developed during ischaemia. Before ischaemia, ERP showed a good correlation with APD (R2 = 0.64) but by one minute of ischaemia the correlation was poor (R2 = 0.29).
CONCLUSIONS—These results show that during the first three minutes of global ischaemia in patients with coronary artery disease: (1) ERP lengthened in response to both a low and a high stimulus strength; and (2) there was a good correlation between ERP and APD before ischaemia, which was lost by one minute as APD decreased and ERP increased. These findings may have important implications in arrhythmogenesis.


Keywords: refractoriness; ischaemia; repolarisation PMID:10995401

  15. Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist

    PubMed Central

    Arumugam, Thiruma V; Arnold, Naomi; Proctor, Lavinia M; Newman, Michelle; Reid, Robert C; Hansford, Karl A; Fairlie, David P; Shiels, Ian A; Taylor, Stephen M

    2003-01-01

    A new group IIa sPLA2 inhibitor was compared with selective inhibitors of COX-1, COX-2 and an LTC4 antagonist for effects on local and remote tissue injuries following ischaemia and reperfusion (I/R) of the small intestine in rats. In an acute model of ischaemia (30 min) and reperfusion (150 min) injury in the absence of inhibitors, there was significant intestinal haemorrhage, oedema and mucosal damage, neutropenia, elevated serum levels of aspartate aminotransferase (AST) and hypotension. Preischaemic treatment with the inhibitor of sPLA2 (Group IIa), at 5 mg kg−1 i.v. or 10 mg kg−1 p.o. significantly inhibited I/R-induced neutropenia, the elevation of serum levels of AST, intestinal oedema and hypotension. Pretreatment with the COX-2 inhibitor celebrex (10 mg kg−1 i.v.) and the LTC4 antagonist zafirlukast (1 mg kg−1 i.v.) also showed marked improvement with I/R-induced AST, oedema and neutropenia. Hypotension was only reduced by the LTC4 antagonist. The COX-1 inhibitor flunixin (1 mg kg−1 i.v.) did not effect improvement in the markers of tissue injury. Histological examination of rat I/R injury showed that all of the drugs offered some protection to the mucosal layer damage compared to no drug treatment. Given i.v., the sPLA2 inhibitor was more effective than either the COX-1 or COX-2 inhibitors in preventing rat I/R injury. These results indicate that a potent new inhibitor of sPLA2 (group IIa) protects the rat small intestine from I/R injury after oral or intravenous administration. COX-2 and LTC4 inhibitors also showed some beneficial effects against intestinal I/R injury. Our study suggests that sPLA2 (Group IIa) may have a pathogenic role in intestinal I/R in rats. PMID:12967936

  16. [The choice of optimal operative intervention in patients, suffering an acute tumoral impassability of large intestine].

    PubMed

    Ioffe, I V; Alekseev, A V; Pepenin, A V; Zhadanov, V I; Lisovoĭ, R V

    2012-03-01

    The results of treatment of 101 patients, suffering an acute ileus (AI), caused by colonic cancer, were presented. The operation was performed in 88 patients for AI in subcompensated and decompensated stages. Right-sided hemicolectomy with ileotransversoanastomosis formation was done for right-sided localization of the tumor in a subcompensated stage. The outloading end colostomy was done after tumoral excision and ileotransversoanastomosis formation accomplishment in patients, suffering AI in a decompensated stage with purulent peritonitis. Obstructive large-bowel resection was performed for left-sided colonic cancer with AI in a decompensated stage, and for subcompensated stage--a left-sided hemicolectomy with Y-type anastomosis was done. Postoperative complications rate have constituted 27.3% and lethality--12.5%.

  17. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction.

    PubMed

    Farah, Roula A; Jalkh, Khalil S; Farhat, Hussein Z; Sayad, Paul E; Kadri, Adel M

    2011-03-01

    We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

  18. Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis

    PubMed Central

    Lutgendorff, Femke; Nijmeijer, Rian M.; Sandström, Per A.; Trulsson, Lena M.; Magnusson, Karl-Eric; Timmerman, Harro M.; van Minnen, L. Paul; Rijkers, Ger T.; Gooszen, Hein G.; Akkermans, Louis M. A.; Söderholm, Johan D.

    2009-01-01

    Background During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. Methodology/Principal Findings Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and 51Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4±33.5 vs. placebo 223.7±93.7 a.u.; P<0.001), 51Cr-EDTA flux (16.7±10.1 vs. 32.1±10.0 cm/s10−6; P<0.005), apoptosis, lipid peroxidation (0.42±0.13 vs. 1.62±0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33±1.47 vs. 8.82±1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33±1.47 vs. 10.70±1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88±1.21 vs. placebo 1.94±0.55 nmol/min/mg protein; P<0

  19. Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation.

    PubMed

    Andres, Ane Miren; Santamaria, Monica; Hernandez-Oliveros, Francisco; Guerra, Laura; Lopez, Sergio; Stringa, Pablo; Vallejo, Maria Teresa; Largo, Carlota; Encinas, Jose Luis; Garcia de Las Heras, Maria Soledad; Lopez-Santamaria, Manuel; Tovar, Juan Antonio

    2016-05-01

    Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature. PMID:27102447

  20. Cocaine use and delayed myocardial ischaemia and/or infarction

    PubMed Central

    Phang, Kee Wei; Wood, Alice

    2014-01-01

    A 37-year-old woman was admitted into the coronary care unit following chest pain after using cocaine. She was found to have significant myocardial ischaemia on blood and ECG investigations despite a recent coronary angiogram that had not demonstrated flow-limiting coronary disease. This case report summarises the risks of myocardial ischaemia and/or infarction for patients taking cocaine and the pathophysiology behind it, focusing in particular on the risks of delayed reaction some time after cocaine ingestion. PMID:25201873

  1. 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.

  2. Immune Response and Intestinal Permeability in Children With Acute Gastroenteritis Treated With Lactobacillus rhamnosus GG: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Sindhu, Kulandaipalayam N. C.; Sowmyanarayanan, Thuppal V.; Paul, Anu; Babji, Sudhir; Ajjampur, Sitara S. R.; Priyadarshini, Sophia; Sarkar, Rajiv; Balasubramanian, K. A.; Wanke, Christine A.; Ward, Honorine D.; Kang, Gagandeep

    2014-01-01

    Background. Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea. Methods. Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up. Results. Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability. Conclusions. LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection. Clinical Trials Registration. CTRI/2010/091/000339. PMID:24501384

  3. Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells

    PubMed Central

    Lee, In-Ah; Low, Daren; Kamba, Alan; Llado, Victoria; Mizoguchi, Emiko

    2013-01-01

    Background The initial trigger of inflammatory bowel disease (IBD) can be partly attributed towards the interaction and invasion of intestinal epithelial cells (IECs) and submucosal compartments. Identifying safe and economical methods to block these interactions may help prevent the onset of early colitis. Chitinase 3-like 1 is an inducible host protein that facilitates bacterial attachment and invasion on/into IECs. Therefore, we test the hypothesis of inhibiting CHI3L1 using the pan-chitinase inhibitor caffeine to reduce the likelihood of early colitis onset. Methods IEC lines were treated with caffeine (2.5 mM or 5 mM) and analyzed for CHI3L1 expression and the impact on bacterial invasion. In vivo, mice were treated with 2.5 mM caffeine and induced with 3.5% dextran sulfate sodium (DSS)-mediated colitis and subsequently analyzed colitis development. Results In vitro, caffeine treatment in IEC lines down-regulated CHI3L1 mRNA expression, which resulted in the reduction of bacterial invasion in a caffeine dose-dependent manner. In vivo, mice treated with caffeine displayed delayed response towards DSS-induced colitis, characterized by lower body weight loss, clinical and histological scores. Bacterial translocation into other organs and pro-inflammatory cytokines production were also reduced in the caffeine-treated mice with DSS-induced colitis. Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo. Conclusion Development of acute colitis is reduced upon caffeine treatment. The mechanism involves the down-regulation of CHI3L1 expression and its associated bacterial interaction effect. Therefore caffeine is proposed as a safe and economical candidate for successful IBD management. PMID:23925589

  4. Novel guggulsterone derivative GG-52 inhibits NF-kappaB signaling in intestinal epithelial cells and attenuates acute murine colitis.

    PubMed

    Kim, Jung Mogg; Kang, Hyoun Woo; Cha, Mi Yeon; Yoo, Doyoung; Kim, Nayoung; Kim, In-Kyoung; Ku, Jeounghun; Kim, Sunil; Ma, Sang-Ho; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung

    2010-07-01

    We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappaB (NF-kappaB) signaling in intestinal epithelial cells (IECs) and to attenuate dextran sulfate sodium (DSS)-induced colitis. This study investigates the anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive and therapeutic murine models of DSS-induced colitis. Novel guggulsterone derivates with high lipophilicity were designed and four derivates, including GG-46, GG-50B, GG-52, and GG-53, were synthesized. Two guggulsterone derivatives, GG-50B and GG-52, significantly inhibited the activated NF-kappaB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). Pretreatment with GG-50B and GG-52 attenuated the increased IkappaB kinase (IKK) and IkappaBalpha phsophorylation induced by TNF-alpha. In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappaB activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases.

  5. Left ventricular dysfunction following transient ischaemia induced by transluminal coronary angioplasty. Beneficial effects of calcium antagonists against post-ischaemic myocardial stunning.

    PubMed

    Sheiban, I; Tonni, S; Benussi, P; Marini, A; Trevi, G P

    1993-07-01

    Acute and severe ischaemia is followed by depression of myocardial contractility during reperfusion; return to full recovery might take a long time. This phenomenon, termed myocardial stunning, has been extensively demonstrated in experimental studies and in different clinical settings. The beneficial effects of calcium antagonists in preventing post-ischaemic myocardial stunning have been tested in experimental studies, showing that when administered before or during ischaemia, they inhibit post-ischaemic myocardial dysfunction. The present study was undertaken to verify the possible occurrence of myocardial stunning following transient ischaemia induced by coronary angioplasty. The aim was also to evaluate the possible protective effects of calcium antagonists (nisoldipine) and nitrates against myocardial stunning in patients with coronary artery disease undergoing routine coronary angioplasty (PCTA) with prolonged inflation. The study included 25 patients, aged between 40 and 69 years, with exercise-induced angina and single vessel disease. The stenosis was severe (80% to subtotal occlusion), localized on the left anterior descending artery, but without collaterals at coronary angiogram. All patients had normal left ventricular (LV) overall function and normal systolic thickening of the anterior wall supplied by the diseased artery. Our data suggest that post-ischaemic myocardial stunning is not only an experimental curiosity, but that it does occur in different clinical settings. Calcium antagonists (i.e. nisoldipine), when added before or during ischaemia, seem to prevent myocardial stunning. These findings confer a potential role to these agents in the treatment of post-ischaemic myocardial dysfunction.

  6. Human baroreflex rhythms persist during handgrip and muscle ischaemia

    PubMed Central

    Eckberg, D. L.; Cooke, W. H.; Diedrich, A.; Levine, B. D.; Pawelczyk, J. A.; Buckey, J. C.; Ertl, A. C.; Biaggioni, I.; Cox, J. F.; Robertson, D.; Baisch, F. J.; Blomqvist, C. G.; Kuusela, T. A.; Tahvanainen, K. U. O.

    2013-01-01

    Aim To determine if physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia, and recovery. Methods We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40 % maximum capacity to exhaustion, post-exercise forearm ischaemia, and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures, and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25 s window moved by 2 s steps) systolic pressure – R-R interval transfer function at 0.04 – 0.15 Hz. Results Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at ~ 0.06 Hz – a period of about 18 s); however, during exercise, most oscillations were at low gain levels, and during ischaemia and recovery, most oscillations were at high gain levels. Conclusions Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery. PMID:23809494

  7. Hydrogen sulfide: physiological properties and therapeutic potential in ischaemia.

    PubMed

    Bos, Eelke M; van Goor, Harry; Joles, Jaap A; Whiteman, Matthew; Leuvenink, Henri G D

    2015-03-01

    Hydrogen sulfide (H2 S) has become a molecule of high interest in recent years, and it is now recognized as the third gasotransmitter in addition to nitric oxide and carbon monoxide. In this review, we discuss the recent literature on the physiology of endogenous and exogenous H2 S, focusing upon the protective effects of hydrogen sulfide in models of hypoxia and ischaemia.

  8. Dislocated ankle fracture complicated by near total distal ischaemia

    PubMed Central

    Duygun, Fatih; Sertkaya, Omer; Aldemir, Cengiz; Dogan, Ali

    2013-01-01

    Total arterial ischaemia is rarely seen following a dislocated ankle fracture but if it does and intervention is not made, it can lead to serious morbidity. We present a 39-year-old woman with almost total occlusion in the arteria tibialis and arteria dorsalis pedis following a dislocated ankle fracture as a result of a bicycle fall. PMID:24248319

  9. NOD2 regulates CXCR3-dependent CD8+ T cell accumulation in intestinal tissues with acute injury.

    PubMed

    Wu, Xingxin; Lahiri, Amit; Haines, G Kenneth; Flavell, Richard A; Abraham, Clara

    2014-04-01

    Polymorphisms in NOD2 confer risk for Crohn's disease, characterized by intestinal inflammation. How NOD2 regulates both inflammatory and regulatory intestinal T cells, which are critical to intestinal immune homeostasis, is not well understood. Anti-CD3 mAb administration is used as therapy in human autoimmune diseases, as well as a model of transient intestinal injury. The stages of T cell activation, intestinal injury, and subsequent T tolerance are dependent on migration of T cells into the small intestinal (SI) lamina propria. Upon anti-CD3 mAb treatment of mice, we found that NOD2 was required for optimal small intestinal IL-10 production, in particular from CD8(+) T cells. This requirement was associated with a critical role for NOD2 in SI CD8(+) T cell accumulation and induction of the CXCR3 ligands CXCL9 and CXCL10, which regulate T cell migration. NOD2 was required in both the hematopoietic and nonhematopoietic compartments for optimal expression of CXCR3 ligands in intestinal tissues. NOD2 synergized with IFN-γ to induce CXCL9 and CXCL10 secretion in dendritic cells, macrophages, and intestinal stromal cells in vitro. Consistent with the in vitro studies, during anti-CD3 mAb treatment in vivo, CXCR3 blockade, CD8(+) T cell depletion, or IFN-γ neutralization each inhibited SI CD8(+) T cell recruitment, and reduced chemokine expression and IL-10 expression. Thus, NOD2 synergizes with IFN-γ to promote CXCL9 and CXCL10 expression, thereby amplifying CXCR3-dependent SI CD8(+) T cell migration during T cell activation, which, in turn, contributes to induction of both inflammatory and regulatory T cell outcomes in the intestinal environment. PMID:24591373

  10. The impact of ischaemia-reperfusion on the blood vessel.

    PubMed

    Gourdin, Maximilien J; Bree, Bernard; De Kock, Marc

    2009-07-01

    Ischaemia significantly affects the cellular homeostasis (sodium and calcium overload, intracellular acidosis, swelling, cytoskeleton injuries, mitochondrial hypercalcaemia and others). If reperfusion of an organ in ischaemia is essential for its viability and its functional recovery, the arrival of blood oxygen will cause a series of lesions; this is known as the phenomenon of ischaemia-reperfusion. Vasomotricity and the endothelial functions are significantly affected by it. Endothelium-dependent vasodilatation is more affected by ischaemia-reperfusion injuries than vasoconstriction and endothelial-independent vasodilatation. Reactive oxygen species and tumour necrosis factor-alpha seem to play a major role in this perturbation. Reperfusion also induces an important inflammatory response, characterized by a massive production of free radicals and by the activation of the complement and leucocyte neutrophils. A narrow interaction between activated endothelium and neutrophils will result in a significant concentration of neutrophils activated in the interstitium, where they release many oxygen radicals and many kinds of proteases, which destroy cells and extracellular matrix. This transfer of neutrophils from the intravascular bed to the intestitium involves several families of proteins such as selectins (P-selectin and L-selectin), integrines (intercellular adhesion molecule-1) and immunoglobulins (platelet-endothelial cell adhesion molecule-1). Last, oxidative stress, the production of cytokines and the secondary mitochondrial lesions that occur with reperfusion will induce apoptosis on the level of the parenchyma and the vascular structures. According to the stage of the vascular system considered (small arteries, capillaries or postcapillary veins), the repercussions of ischaemia-reperfusion are identical, but the clinical pictures differ. The proinflammatory state induced by reperfusion continues for several days and can affect the patient's prognosis. PMID

  11. 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

  12. High-sensitivity troponin assay improves prediction of cardiovascular risk in patients with cerebral ischaemia

    PubMed Central

    Stahrenberg, Raoul; Niehaus, Cord-Friedrich; Edelmann, Frank; Mende, Meinhard; Wohlfahrt, Janin; Wasser, Katrin; Seegers, Joachim; Hasenfuß, Gerd; Gröschel, Klaus; Wachter, Rolf

    2013-01-01

    Background and purpose Clinical scores are recommended for predicting cardiovascular risk in patients with cerebral ischaemia to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores. Methods Within the observational Find-AF trial (ISRCTN46104198), 197 patients >18 years of age with cerebral ischaemia and without atrial fibrillation had blood sampled at baseline. The predictive value of five biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to the Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2) and National Institutes of Health Stroke Scale (NIH-SS). Results There were 23 vascular events (11.7%) and 13 deaths (6.6%) to 1 year follow-up. In multivariate analyses of all markers, only high-sensitivity troponin T (hsTropT) remained independently predictive for vascular events (p=0.045) and all-cause mortality (p=0.004). hsTropT was higher in patients with a vascular event (median 12.7 ng/ml vs 5.1 ng/ml), and patients with hsTropT above the median of 6.15 ng/ml had vascular events more frequently (HR 3.86, p=0.008). For prediction of vascular events as well as all-cause mortality, hsTropT significantly improved multivariate Cox regression models with ESRS, SPI-2 or NIH-SS. The c-statistic increased non-significantly from 0.695 (ESRS) or 0.710 (hsTropT) to 0.747 (ESRS+hsTropT) and from 0.699 (SPI-2) to 0.763 (SPI-2+hsTropT). No patient with a low-risk ESRS and an hsTropT below the median had a vascular event or died. Conclusions hsTropT predicts vascular events and all-cause mortality in patients with acute cerebral ischaemia and improves prediction beyond established clinical scores. PMID:23355808

  13. [INCIDENCE, PREDISPOSING RISK FACTORS FOR THE DEVELOPMENT AND SPREADING OF ACUTE INTESTINAL INFECTIONS IN THE NORTH-EASTERN REGION OF UKRAINE].

    PubMed

    Malysh, N G; Chemych, N D; Zaritsky, A M

    2016-01-01

    Using data of the branch statistical reporting of the State Sanitary and Epidemiological Service in Sumy region and Sumy Regional State Laboratory of Veterinary Medicine, the incidence rate, modern risk factors for the development and spreading of acute infectious diarrheas were determined in the North-Eastern region of Ukraine. Under the current conditions incidence rate indices of acute intestinal infections and food toxicoinfections are within the range of 159.8-193.6 per 100 thousands. pop. Seasonal and epidemical rises are associated with a species of the agent. In the etiological structure of acute diarrheal infections there are dominated viruses, of food toxicoinfections--Klebsiellae pneumoniae, Staphylococcus aureus and Enterobacter cloacae (p < 0.05). Predictors of the complication of epidemiological situation of Shigella infections are the gain in the detection of bacterially contaminated samples of milk and dairy products (r = 0.75), for food toxicoinfections caused by Klebsiellae pneumoniae and Enterobacter cloacae--pastry with cream and cooking meat products (r = 0.64; r = 0.75). Epizootic situation in the region affects on the salmonellosis incidence rate of the population (r = 0.89). There were revealed correlations between the selection of E. coli bacteria from swabs taken from the enterprises of catering, in child care centers and the levels of incidence rates of salmonellosis, acute intestinal infections of unknown etiology (r = 0.59; r = 0.60). Timely detection and sanitation of Shigella carriers are a powerful instrument to reduce the incidence rate of shigellosis (r = 0.83). PMID:27266031

  14. [INCIDENCE, PREDISPOSING RISK FACTORS FOR THE DEVELOPMENT AND SPREADING OF ACUTE INTESTINAL INFECTIONS IN THE NORTH-EASTERN REGION OF UKRAINE].

    PubMed

    Malysh, N G; Chemych, N D; Zaritsky, A M

    2016-01-01

    Using data of the branch statistical reporting of the State Sanitary and Epidemiological Service in Sumy region and Sumy Regional State Laboratory of Veterinary Medicine, the incidence rate, modern risk factors for the development and spreading of acute infectious diarrheas were determined in the North-Eastern region of Ukraine. Under the current conditions incidence rate indices of acute intestinal infections and food toxicoinfections are within the range of 159.8-193.6 per 100 thousands. pop. Seasonal and epidemical rises are associated with a species of the agent. In the etiological structure of acute diarrheal infections there are dominated viruses, of food toxicoinfections--Klebsiellae pneumoniae, Staphylococcus aureus and Enterobacter cloacae (p < 0.05). Predictors of the complication of epidemiological situation of Shigella infections are the gain in the detection of bacterially contaminated samples of milk and dairy products (r = 0.75), for food toxicoinfections caused by Klebsiellae pneumoniae and Enterobacter cloacae--pastry with cream and cooking meat products (r = 0.64; r = 0.75). Epizootic situation in the region affects on the salmonellosis incidence rate of the population (r = 0.89). There were revealed correlations between the selection of E. coli bacteria from swabs taken from the enterprises of catering, in child care centers and the levels of incidence rates of salmonellosis, acute intestinal infections of unknown etiology (r = 0.59; r = 0.60). Timely detection and sanitation of Shigella carriers are a powerful instrument to reduce the incidence rate of shigellosis (r = 0.83).

  15. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  16. Oct-2 transcription factor binding activity and expression up-regulation in rat cerebral ischaemia is associated with a diminution of neuronal damage in vitro.

    PubMed

    Camós, Susanna; Gubern, Carme; Sobrado, Mónica; Rodríguez, Rocío; Romera, Víctor G; Moro, María Ángeles; Lizasoain, Ignacio; Serena, Joaquín; Mallolas, Judith; Castellanos, Mar

    2014-06-01

    Brain plasticity provides a mechanism to compensate for lesions produced as a result of stroke. The present study aims to identify new transcription factors (TFs) following focal cerebral ischaemia in rat as potential therapeutic targets. A transient focal cerebral ischaemia model was used for TF-binding activity and TF-TF interaction profile analysis. A permanent focal cerebral ischaemia model was used for the transcript gene analysis and for the protein study. The identification of TF variants, mRNA analysis, and protein study was performed using conventional polymerase chain reaction (PCR), qPCR, and Western blot and immunofluorescence, respectively. Rat cortical neurons were transfected with small interfering RNA against the TF in order to study its role. The TF-binding analysis revealed a differential binding activity of the octamer family in ischaemic brain in comparison with the control brain samples both in acute and late phases. In this study, we focused on Oct-2 TF. Five of the six putative Oct-2 transcript variants are expressed in both control and ischaemic rat brain, showing a significant increase in the late phase of ischaemia. Oct-2 protein showed neuronal localisation both in control and ischaemic rat brain cortical slices. Functional studies revealed that Oct-2 interacts with TFs involved in important brain processes (neuronal and vascular development) and basic cellular functions and that Oct-2 knockdown promotes neuronal injury. The present study shows that Oct-2 expression and binding activity increase in the late phase of cerebral ischaemia and finds Oct-2 to be involved in reducing ischaemic-mediated neuronal injury.

  17. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs

    PubMed Central

    Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production. PMID:25030663

  18. Selective Exposure of the Fetal Lung and Skin/Amnion (but Not Gastro-Intestinal Tract) to LPS Elicits Acute Systemic Inflammation in Fetal Sheep

    PubMed Central

    Saito, Masatoshi; Newnham, John P.; Cox, Tom; Jobe, Alan H.; Kramer, Boris W.; Kallapur, Suhas G.

    2013-01-01

    Inflammation of the uterine environment (commonly as a result of microbial colonisation of the fetal membranes, amniotic fluid and fetus) is strongly associated with preterm labour and birth. Both preterm birth and fetal inflammation are independently associated with elevated risks of subsequent short- and long-term respiratory, gastro-intestinal and neurological complications. Despite numerous clinical and experimental studies to investigate localised and systemic fetal inflammation following exposure to microbial agonists, there is minimal data to describe which fetal organ(s) drive systemic fetal inflammation. We used lipopolysaccharide (LPS) from E.coli in an instrumented ovine model of fetal inflammation and conducted a series of experiments to assess the systemic pro-inflammatory capacity of the three major fetal surfaces exposed to inflammatory mediators in pregnancy (the lung, gastro-intestinal tract and skin/amnion). Exposure of the fetal lung and fetal skin/amnion (but not gastro-intestinal tract) caused a significant acute systemic inflammatory response characterised by altered leucocytosis, neutrophilia, elevated plasma MCP-1 levels and inflammation of the fetal liver and spleen. These novel findings reveal differential fetal organ responses to pro-inflammatory stimulation and shed light on the pathogenesis of fetal systemic inflammation after exposure to chorioamnionitis. PMID:23691033

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

    SciTech Connect

    Vavassori, Vittorio; Fiorino, Claudio . E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Magli, Alessandro; Fellin, Gianni; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Valdagni, Riccardo

    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 1,132 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 predictive for

  20. Oral infection with enteropathogenic Escherichia coli triggers immune response and intestinal histological alterations in mice selected for their minimal acute inflammatory responses.

    PubMed

    Vulcano, Amanda Bardella; Tino-De-Franco, Milene; Amaral, José Araujo; Ribeiro, Orlando Garcia; Cabrera, Wafa Hanna Koury; Bordenalli, Marcela Aparecida; Carbonare, Cristiane Barros; Álvares, Eliana Parisi; Carbonare, Solange Barros

    2014-06-01

    Enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea, is an important public health problem in Brazil and other developing countries. In vitro assays of bacterial adhesion to cultured cells are important tools for studying bacterial pathogenicity but do not reproduce all the events that occur in natural infections. In this study, the effects of oral infection with EPEC on mice selected for their minimal acute inflammatory response (AIR min) were evaluated. Mice were orally infected with EPEC and variations in body weight, bacterial shedding and antibody production observed. The infected animals developed seric and secretory anti-EPEC antibodies; however, neither mortality nor diarrhea was observed. Light microscopy of their intestines demonstrated histological modifications that were not present in controls. However, electron microscopy did not show bacteria attached to the intestinal epithelia to form attaching and effacing lesions, characteristic of EPEC in humans. The bacteria were detected in Peyer's patches and intestinal contents up to 5 hr post-infection. When human anti-EPEC secretory immunoglobulin A or avian immunoglobulin Y antibodies were administered to infected animals, they developed minor histological alterations compared with non-treated animals. In summary, it was found that EPEC triggers immune responses and intestinal histological alterations but does not produce evidence of diarrheal disease in mice infected by the oral route. This study of EPEC experimental infection provides a better understanding of the effects of antibodies on bacterial infections and may provide a suitable model for the design and testing of immunobiological products for active or passive immunization. PMID:24750489

  1. Digital ischaemia: a rare but severe complication of jellyfish sting.

    PubMed

    Lam, Stacey C; Hung, Y W; Chow, Esther C S; Wong, Clara W Y; Tse, W L; Ho, P C

    2014-10-01

    We report a case of digital ischaemia in a 31-year-old man who presented with sudden hand numbness, swelling, and cyanosis 4 days after a jellyfish sting. This is a rare complication of jellyfish sting, characterised by a delayed but rapid downhill course. Despite serial monitoring with prompt fasciotomy and repeated debridement, he developed progressive ischaemia in multiple digits with gangrenous change. He subsequently underwent major reconstructive surgery and aggressive rehabilitation. Although jellyfish stings are not uncommon, no severe jellyfish envenomation has been reported in the past in Hong Kong and there has not been any consensus on the management of such injuries. This is the first local case report of jellyfish sting leading to serious hand complications. This case revealed that patients who sustain a jellyfish sting deserve particular attention to facilitate early detection of complications and implementation of therapy.

  2. 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

  3. Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

    PubMed Central

    Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-01

    Background Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Methodology/Principal Findings Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. Conclusions This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies. PMID:18231608

  4. Influence of glycaemic control on the outcomes of patients treated by intravenous thrombolysis for cerebral ischaemia.

    PubMed

    Litke, Rachel; Moulin, Solène; Cordonnier, Charlotte; Fontaine, Pierre; Leys, Didier

    2015-11-01

    Whether the glycaemic control during the first hours of cerebral ischaemia treated by thrombolysis influences outcomes remains unsettled. We aimed at evaluating the quality of the glycaemic control and whether patients with well-controlled glycaemia after thrombolysis for acute cerebral ischaemia have better outcomes. We retrospectively analysed data prospectively collected in consecutive stroke patients who received i.v. thrombolysis at the Lille University Hospital. Patients with glycaemia >1.6 g/l (8.9 mmol/l) at any point during the first 48 h received insulin. We used 2 definitions of well controlled glycaemia: (i) "well controlled 100 %" when 100 % glycaemia were <1.6 g/l (8.9 mmol/l), and (ii) "well controlled 70 %" when at least 70 % glycaemia were <1.6 g/l (8.9 mmol/l). The outcome measures at 3 months were (1) independence [modified Rankin scale (mRS) score 0 or 1], (2) absence of handicap (mRS 0-2), (3) death, and (4) symptomatic intracerebral haemorrhage (sICH). Of 875 consecutive patients, 657 (75.2 %) were considered as well controlled with a threshold at 100 % and 736 (84.2 %) with a threshold at 70 %. The glycaemic control was not independently associated with any of the four outcome measures. In patients treated by insulin, hypoglycaemic events were rare (2.1 % of all patients) and of moderate intensity [>0.5 g/l (2.8 mmol/l)]. The quality of the glycaemic control was not associated with outcomes in patients treated by thrombolysis. A possible explanation is that the glycaemic control after thrombolysis has minor influence compared with glycaemic control before thrombolysis when the artery is not yet re-open and the penumbra area at maximum. PMID:26275565

  5. Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy.

    PubMed

    Nelson, Michael D; Rosenberry, Ryan; Barresi, Rita; Tsimerinov, Evgeny I; Rader, Florian; Tang, Xiu; Mason, O'Neil; Schwartz, Avery; Stabler, Thomas; Shidban, Sarah; Mobaligh, Neigena; Hogan, Shomari; Elashoff, Robert; Allen, Jason D; Victor, Ronald G

    2015-12-01

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. BMD is caused by in-frame mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the sarcolemma. Among these is neuronal nitric oxide synthase mu (nNOSμ), which requires specific spectrin-like repeats (SR16/17) in dystrophin's rod domain and the adaptor protein α-syntrophin for sarcolemmal targeting. When healthy skeletal muscle is exercised, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates α-adrenergic vasoconstriction, thus optimizing perfusion. In the mdx mouse model of dystrophinopathy, this protective mechanism (functional sympatholysis) is defective, resulting in functional muscle ischaemia. Treatment with a NO-donating non-steroidal anti-inflammatory drug (NSAID) alleviates this ischaemia and improves the murine dystrophic phenotype. In the present study, we report that, in 13 men with BMD, sympatholysis is defective mainly in patients whose mutations disrupt sarcolemmal targeting of nNOSμ, with the vasoconstrictor response measured as a decrease in muscle oxygenation (near infrared spectroscopy) to reflex sympathetic activation. Then, in a single-arm, open-label trial in 11 BMD patients and a double-blind, placebo-controlled cross-over trial in six patients, we show that acute treatment with oral sodium nitrate, an inorganic NO donor without a NSIAD moiety, restores sympatholysis and improves post-exercise hyperaemia (Doppler ultrasound). By contrast, sodium nitrate improves neither sympatholysis, nor hyperaemia in healthy controls. Thus, a simple NO donor recapitulates the vasoregulatory actions of sarcolemmal nNOS in BMD patients, and constitutes a putative novel therapy for this disease.

  6. Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis

    SciTech Connect

    Ramage, J.K.; Stanisz, A.; Scicchitano, R.; Hunt, R.H.; Perdue, M.H.

    1988-06-01

    In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens.

  7. Colon-derived uremic biomarkers induced by the acute toxicity of Kansui radix: A metabolomics study of rat plasma and intestinal contents by UPLC-QTOF-MS(E).

    PubMed

    Yang, Zhou; Hou, Jin-Jun; Qi, Peng; Yang, Min; Yan, Bing-Peng; Bi, Qi-Rui; Feng, Rui-Hong; Yang, Wen-Zhi; Wu, Wan-Ying; Guo, De-An

    2016-07-15

    Kansui radix (KR) is a poisonous Chinese herbal medicine recorded in the Chinese Pharmacopoeia, and the acute toxicity obstructs its clinical applications. To explore its acute toxicity mechanism to enhance clinical safety, a metabolomics study based on UPLC-ESI-QTOF-MS(E) was performed. Wistar rats were exposed for 4h to the aqueous and ethyl acetate extracts prepared from KR at a high dose (25g/kg). The contents of six different sections of rat intestine, including the duodenum, jejunum, ileum, cecum, colon, and rectum were collected as samples for the first time, as well as the rat plasma. The interesting results showed that only those rats exposed to the ethyl acetate extract showed a watery diarrhea, similar to the observed acute human toxicity. The identified biomarkers found in the plasma, such as phenol sulfate, indoxyl sulfate, and p-cresol sulfate were significantly perturbed in the rats. These biomarkers are known as colon-derived uremic compounds, which were first reported with respect to KR. The three essential amino acids which produced these biomarkers were only found in the contents of colon and rectum. A hypothesis was proposed that only the colon-derived uremic compounds induced by KR might be responsible for the acute toxicity. Three traditional process methods to reduce the toxicity of KR were compared based on these biomarkers, and different levels of toxicity modulation were observed. These results may be helpful to further understand the mechanism of acute toxicity, and the relevance of the traditional process methods to ameliorate the adverse effects of KR.

  8. Effect of Bovine Lactoferrin Treatment Followed by Acute Stress on the IgA-Response in Small Intestine of BALB/c Mice.

    PubMed

    Peña-Juárez, Ma Concepción; Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Cruz-Hernández, Teresita Rocío; Reyna-Garfias, Humberto; Barbosa-Cabrera, Reyna Elizabeth; Drago-Serrano, Maria Elisa

    2016-10-01

    Secretory IgA (SIgA) has a pivotal role in gut homeostasis, which can be disturbed by stress. SIgA is formed by IgA-dimers (associated by the J-chain) and the secretory component, a protein derivative of polymeric immunoglobulin receptor (pIgR). Given the gut immuno-modulatory properties of bovine lactoferrin (bLf), the aim of this study was to compare, after bLf treatment followed by acute stress, the IgA response and IgA-associated parameters in proximal versus distal small intestine. Male BALB/c mice (n = 6) were orally treated with bLf (50, 500, and 5000 μg) for 7 days, then stressed by immobilization for 1 h, and sacrificed. In proximal and distal segments, levels were determined of IgA in gut secretions (enzyme-linked immunosorbent assay [ELISA]), the α-/J-chain and pIgR proteins in epithelial cells (Western-blot), and mRNA expression of the α-/J-chain, pIgR, and interleukins (ILs) in mucosa (RT-PCR). Data were compared by two-way analysis of variance (ANOVA) (significance at P < 0.05). Under acute stress, bLf triggered higher levels of IgA, SIgA, and anti-bLf-IgA as well as greater mRNA expression of pIgR, IL-4, and IL-6 (500 µg) in proximal intestine, while inducing higher levels of the total IgA, α-/J-chain, and pIgR proteins as well as greater mRNA expression of the α-chain and IL-4 (5000 µg) in distal intestine. Compared to unstressed/bLf-untreated mice, plasma corticosterone (a stress biomarker, measured by ELISA) increased in stressed/bLf-treated (0, 50 and 500 µg) and unstressed/bLf-treated (5000 µg) mice. The interplay of corticosterone with gut neuroendocrine factors may have elicited signals creating anti-inflammatory conditions for an IgA-response profile in each intestinal region, according to the bLf concentration administered.

  9. The cardioprotective potential of valsartan in myocardial ischaemia reperfusion injury

    PubMed Central

    Hadi, Najah R.; Al-Amran, Fhadil G.; Hussien, Yasmeem A.; Al-Turfy, Mahamed

    2015-01-01

    Background Ischaemia/reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischaemia with inadequate oxygen followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may aggravate local injury as well as induce impairment of remote organ function by mechanisms that involve oxidative stress, inflammation, and apoptosis. Objective This study was undertaken to investigate the potential role of valsartan angiotensin receptor blocker-1 (ARB-1) in the amelioration of myocardial ischaemia/reperfusion injury induced by ligation of coronary artery in a rat model. Material and methods Adult male Albino rats were randomised into four equal groups (seven rats in each group). In group 1 (sham group) the rats underwent the same anaesthetic and surgical procedure as the control group except for ligation of the left anterior descending (LAD) coronary artery; group 2 (control group) rats were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for 2 hours; group 3 (control vehicle group) rats received (normal saline) vehicle of valsartan via IP injection and were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for two hours; group 4 (valsartan treated group) rats were pretreated with valsartan 10 mg/kg IP 30 minutes before ligation of LAD coronary artery. At the end of the experiment, blood samples were taken by direct cardiac puncture for the measurement of plasma levels of troponin T (cTnT) and serum levels for both malondialdehyde MDA and glutathione GSH. After blood sampling, the heart was removed and divided into two parts; the apex was used for histopathological examination, and the remaining part was used for the measurement of cardiac tissue levels of tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), cysteine aspartic acid-protease 3 (caspase-3), and BCL2-associated X

  10. Viral PCR positivity in stool before allogeneic hematopoietic cell transplantation is strongly associated with acute intestinal graft-versus-host disease.

    PubMed

    van Montfrans, Joris; Schulz, Laura; Versluys, Birgitta; de Wildt, Arianne; Wolfs, Tom; Bierings, Marc; Gerhardt, Corinne; Lindemans, Caroline; Wensing, Anne; Boelens, Jaap Jan

    2015-04-01

    Acute graft-versus-host disease (aGVHD) can be triggered by inflammatory conditions, including infections and mucositis. We investigated the association between PCR positivity for gastrointestinal (GI) viruses in stool before hematopoietic cell transplantation (HCT) and intestinal aGVHD using Cox proportional hazard models. We included 48 consecutive HCT patients (28 with malignancies and 20 with nonmalignancies) without GI symptoms before HCT. Fifteen patients were GI virus positive: 9 adenovirus, 3 norovirus, 2 parechovirus, and 1 astrovirus. Overall survival was 58% ± 8%. The cumulative incidence of aGVHD grade 2 to 4 was 43% ± 8% (n = 18) after a median of 47 days (range, 14 to 140). In univariate analysis, GI virus PCR positivity was the only predictor for aGVHD (P = .008): within the group of GI virus PCR-positive patients, the cumulative incidence of aGVHD 2 to 4 was 70% ± 12% versus 29 ± 8% in the PCR-negative group (P = .004). In conclusion, GI virus PCR positivity before HCT predicted development of intestinal aGVHD. These results may ultimately affect monitoring, aGVHD prophylaxis, and treatment, as well as rescheduling of elective HCTs.

  11. The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology

    PubMed Central

    Kleiman, Susan C.; Watson, Hunna J.; Bulik-Sullivan, Emily C.; Huh, Eun Young; Tarantino, Lisa M.; Bulik, Cynthia M.; Carroll, Ian M.

    2015-01-01

    Objective The relevance of the microbe-gut-brain axis to psychopathology is of interest in anorexia nervosa (AN), as the intestinal microbiota plays a critical role in metabolic function and weight regulation. Methods We characterized the composition and diversity of the intestinal microbiota in AN, using stool samples collected at inpatient admission (T1) (n=16) and discharge (T2) (n=10). At T1, participants completed the Beck Depression and Anxiety Inventories and the Eating Disorder Examination-Questionnaire. Patients with AN were compared to healthy individuals who participated in a previous study (healthy comparison group; HCG). Genomic DNA was isolated from stool samples, and bacterial composition was characterized by 454 pyrosequencing of the 16S rRNA gene. Sequencing results were processed by the Quantitative Insights Into Microbial Ecology pipeline. We compared T1 vs. T2 samples, samples from both points were compared to HCG (n=12), and associations between psychopathology and T1 samples were explored. Results In patients with AN, significant changes emerged between T1 and T2 in taxa abundance and beta (between-sample) diversity. Patients with AN had significantly lower alpha (within-sample) diversity than HCG at both T1 (p=0.0001) and T2 (p=0.016), and differences in taxa abundance were found between AN patients and HCG. Levels of depression, anxiety, and eating disorder psychopathology at T1 were associated with composition and diversity of the intestinal microbiota. Conclusions We provide evidence of intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. Future directions include mechanistic investigations of the microbe-gut-brain axis in animal models and association of microbial measures with metabolic changes and recovery indices. PMID:26428446

  12. Ischaemia change with revascularisation versus medical therapy in reduced ejection fraction

    PubMed Central

    Mentz, Robert J; Fiuzat, Mona; Shaw, Linda K; Farzaneh-Far, Afshin; M O'Connor, Christopher; Borges-Neto, Salvador

    2015-01-01

    Objective Nuclear imaging data demonstrate that revascularisation leads to favourable effects on ischaemia burden and improved outcomes compared with medical therapy (MT). In patients with heart failure (HF), the effects of MT versus revascularisation on ischaemia change and its independent prognostic significance requires investigation. Methods From the Duke Databank, we performed a retrospective analysis of 278 consecutive patients with coronary artery disease (CAD) and ejection fraction (EF) ≤40%, who underwent 2 serial myocardial perfusion scans between 1993 and 2009. Ischaemia change was calculated for patients undergoing MT alone, or revascularisation. Cox proportional hazards regression modelling was used to identify factors associated with death/myocardial infarction (MI). Results The magnitude of ischeamia reduction was greater with revascularisation than with MT alone (median change of −6% vs 0%, p<0.001). With revascularisation, more patients experienced ≥5% ischaemia reduction compared with MT (52% vs 25%, p<0.01) and a similar percentage experienced ≥5% ischaemia worsening (13% vs 18%, p=0.37). After risk adjustment, ≥5% ischaemia worsening was associated with decreased death/MI (HR=0.58; 95% CI 0.36 to 0.96). Conclusions In patients with HF with CAD, revascularisation improves long-term ischaemia burden compared with MT. Ischaemia worsening on nuclear imaging was associated with reduced risk of death/MI, potentially related to development of ischaemic viable myocardium as opposed to scar tissue. PMID:26339498

  13. Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease After Donor Stem Cell Transplant

    ClinicalTrials.gov

    2011-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; De Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Gastrointestinal Complications; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Childhood Rhabdomyosarcoma; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent

  14. [Angiosome-directed revascularization of critical limb ischaemia].

    PubMed

    Houlind, Kim

    2015-07-27

    Critical limb ischaemia is the major cause of amputation in the developed world. When performing revascularization of the lower limb, guidelines recommend grafting of the "least diseased distal artery with the best continuous run-off to the ankle/foot... regardless of location" often implying indirect perfusion of the ischaemic area through collaterals. An alter-native strategy, called the "angiosome model", advocates a strategy which provides blood supply directly to the ischaemic area. This paper reviews the current evidence of indirect versus angiosome-directed revascularization of the lower limb.

  15. Experimental regional myocardial ischaemia and myocardial uptake of potassium analogues; intercomparison of 42K, 86Rb and 201Tl.

    PubMed

    Kasalický, J; Mrhová, O; Stýs, V

    1983-01-01

    The uptake of 42K, 86Rb and 201Tl by non-ischaemic and ischaemic myocardium was determined in rats with coronary artery ligature lasting 10, 30, 60 and 120 min, and in control rats without ischaemia. Whereas the myocardial concentration of 201Tl and 42K in control rats was similar and higher than that of 86Rb, 201Tl was superior to the other two radionuclides due to its significantly higher accumulation in non-ischaemic myocardium and the higher ratio of non-ischaemic to ischaemic radioactivity. The 86Rb accumulation in non-ischaemic myocardium and non-ischaemic/ischaemic ratio began to decrease from its maximum at 10 min. 201Tl, 42K and 86Rb blood levels in intact animals decreased rapidly after intravenous injection to low and nearly stabilized values at 5 min. Na+K+-ATPase activity in the ischaemic myocardium was high in the acutely ischaemic myocardium and decreased to below control levels after 4 h of ischaemia; changes in activity could not influence the low uptake of potassium analogues in fresh ischaemic myocardium.

  16. Intestinal transplantation: a review.

    PubMed

    Desai, Chirag Sureshchandra; Khan, Khalid Mahmood; Girlanda, Raffaele; Fishbein, Thomas M

    2012-09-01

    Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80 % survival at 1 year. Patients requiring multivisceral transplants have a high rate of attrition with a 1 year survival less than 70 %. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40 years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.

  17. Acute pancreatitis secondary to duodeno-duodenal intussusception caused by a duodenal membrane, in a patient with intestinal malrotation

    PubMed Central

    Larsen, Pernille Oehlenschläger; Ellebæk, Mark Bremholm; Pless, Torsten; Qvist, Niels

    2015-01-01

    Duodeno-duodenal intussusception is often caused by an intraluminal tumour. The condition is rare owing to the retroperitoneal fixation of the duodenum, which is sometime absent in cases of intestinal malrotation. We describe the case of a 19-year old man admitted to hospital with abdominal pain and vomiting. A CT scan revealed a duodeno-duodenal intussusception including the head of the pancreas, which was confirmed by laparotomy. The cause was found to be a duodenal membrane with a pinhole passage combined with non-rotation of the duodenum. PMID:26117447

  18. [Prophylaxis, diagnosis and conservative treatment of chronic lower extremities ischaemia].

    PubMed

    Ruszkiewicz, Cezary B

    2005-01-01

    The most frequent cause underlying the chronic lower extremities ischaemia is atheromatosis. As the basic symptom of the disease, intermittent claudication exerts essential impact upon the state of patient's health as it causes the limitation or the loss of the ability of unassisted walking and, effectively, also the deterioration of the quality of his or her life. The discovery of the etiopathogenesis of atheromatosis and correct assessment of risk factors involved are the elementary conditions of proper administering of pharmacological treatment as well as the basis for adequate planning of necessary prophylactic steps. In such cases, the diagnostic process ought to involve obtaining data from the patient's medical history and his or her physical examination, as well as determining his or her ankle-brachial index (ABI) and information derived from ultrasonographic examination performed at non-invasive diagnostics laboratory. The resultant treatment ought to focus on the improvement of the patient's functional efficiency. Before the necessity of surgical treatment is considered it is recommended to determine a plan for conservative treatment. Adequate diagnosis combined with an early commencement of conservative treatment in the cases of chronic lower extremities ischaemia frequently prove effective in arresting the development of the disease and, consequently, render invasive treatment unnecessary--thus resulting in the improvement of patient's quality of life.

  19. Rapid cooling after acute hyperthermia alters intestinal tissue morphology and increases the systemic inflammatory response in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute hyperthermia can result in mortality if recovery is not appropriately managed. The study objective was to determine the effects of heatstroke recovery methods on the physiological response in pigs. In four repetitions, 36 male pigs (88.7 ± 1.6 kg BW) were exposed to thermoneutral conditions (T...

  20. Intestinal leiomyoma

    MedlinePlus

    Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...

  1. 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 ...

  2. Loss of TMF/ARA160 Protein Renders Colonic Mucus Refractory to Bacterial Colonization and Diminishes Intestinal Susceptibility to Acute Colitis*

    PubMed Central

    Bel, Shai; Elkis, Yoav; Lerer-Goldstein, Tali; Nyska, Abraham; Shpungin, Sally; Nir, Uri

    2012-01-01

    TMF/ARA160 is a Golgi-associated protein with several cellular functions, among them direction of the NF-κB subunit, p65 RelA, to ubiquitination and proteasomal degradation in stressed cells. We sought to investigate the role of TMF/ARA160 under imposed stress conditions in vivo. TMF−/− and wild-type (WT) mice were treated with the ulcerative agent dextran sulfate sodium (DSS), and the severity of the inflicted acute colitis was determined. TMF−/− mice were found to be significantly less susceptible to DSS-induced colitis, with profoundly less bacterial penetration into the colonic epithelia. Surprisingly, unlike in WT mice, no bacterial colonies were visualized in colons of healthy untreated TMF−/− mice, indicating the constitutive resistance of TMF−/− colonic mucus to bacterial retention and penetration. Gene expression analysis of colon tissues from unchallenged TMF−/− mice revealed 5-fold elevated transcription of the muc2 gene, which encodes the major component of the colonic mucus gel, the MUC2 mucin. Accordingly, the morphology of the colonic mucus in TMF−/− mice was found to differ from the mucus structure in WT colons. The NF-κB subunit, p65, a well known transcription inducer of muc2, was up-regulated significantly in TMF−/− intestinal epithelial cells. However, this did not cause spontaneous inflammation or increased colonic crypt cell proliferation. Collectively, our findings demonstrate that absence of TMF/ARA160 renders the colonic mucus refractory to bacterial colonization and the large intestine less susceptible to the onset of colitis. PMID:22553199

  3. Abnormal postural reflexes in a patient with pontine ischaemia.

    PubMed

    Cantello, Roberto; Magistrelli, Luca; Terazzi, Emanuela; Grossini, Elena

    2015-01-01

    The control of body posture is a complex activity that needs a very close relationship between different structures, such as the vestibular system, and the muscle and joint receptors of the neck. Damage of even one of these structures can lead to abnormal postural reflexes. We describe a case of a woman with a left pontine ischaemia who developed a 'dystonic' extensor posture of the left limbs while turned on the right side. This clinical picture differs from previous reports on the subject, and may relate to ischaemic damage of a pontine structure involved in posture control, or of adjacent neural connections to be yet identified. To the best of our knowledge, this is the first case reported in the literature. Clinical examples of an altered interplay between vestibular and neck receptors are rare. PMID:26561222

  4. Correlation between angiographic findings and the ischaemia of head injury.

    PubMed Central

    Macpherson, P; Graham, D I

    1978-01-01

    The carotid angiograms of 96 patients who had died from non-missile head injury were reviewed and assessed for evidence of arterial spasm, slowing of the cerebral circulation, and the presence of intracranial haemotoma. As bilateral angiography had been done in 44 cases the results are based on a correlation between the angiographic appearances and the presence or absence of ischaemic brain damage in the cortex of 140 cerebral hemispheres. There was a significant relationship between spasm alone, the presence of intracranial haematoma alone, or their combination, and ischaemic damage in the ipsilateral cortex. Apart from an association between the more severe grades of spasm and slowing of circulation in the group with ischaemia within arterial territories, there was none between slowing of the circulation or the combination of slowing with either spasm or haematoma and ischaemic brain damage. PMID:632819

  5. Permeability of the small intestine to (/sup 51/Cr)EDTA in children with acute gastroenteritis or eczema

    SciTech Connect

    Forget, P.; Sodoyez-Goffaux, F.; Zappitelli, A.

    1985-06-01

    Increased gut permeability to macromolecules is thought to be an important factor in the development of food hypersensitivity. The latter can develop in the course of acute gastroenteritis and could play a role in infantile eczema. The authors studied gut permeability in 10 normal adults, 11 control children, 7 children with acute gastroenteritis, and 8 patients with infantile eczema, making use of (/sup 51/Cr)EDTA as probe molecule. (/sup 51/Cr)EDTA was given orally (50-100 microCi); 24-h urinary excretion of (/sup 51/Cr)EDTA was measured and expressed as a percentage of the oral dose. Mean and standard error were 2.35 +/- 0.24, 2.51 +/- 0.21, 9.96 +/- 3.44, and 10.90 +/- 2.05 in normal adults, control children, and gastroenteritis and eczema patients, respectively. Differences between controls and either gastroenteritis (p less than 0.001) or eczema (p less than 0.001) patients are significant. The results support the hypothesis that increased gut permeability could play a role in food hypersensitivity.

  6. [DISTRIBUTION OF BACTERIA OF THE KLEBSIELLA STRAIN IN WATER OBJECTS AND THEIR VALUE IN DEVELOPING OF THE WATER CAUSED ACUTE INTESTINAL INFECTIONS].

    PubMed

    Rakhmanin, Yu A; Ivanova, L V; Artyomova, T Z; Gipp, E K; Zagaynova, A V; Maksimkina, T N; Krasnyak, A V; Zhuravlev, P V; Aleshnya, V V; Panasovets, O P

    2016-01-01

    The wide circulation of Klebsiella bacteria in water ofwater objects of different climatic zones of Russia and various function is established. So bacteria of the Klebsiella strain are in superficial sources of the centralized water supply depending on extent of their biological and chemical pollution; underground waters at the unprotected water-bearing horizons; in drinking water at insufficiently effective system of its cleaning and disinfecting. Klebsiella circulating in water was shown to keep properties of pathogenicity and a virulence, possess resistance both to modern preparations and disinfecting agents (chlorine, an ultraviolet to radiation). Bacteria of the Klebsiella strain have high penetration in the water-bearing horizons. At strains of Klebsiella there is allocated considerable pathogenic potential (adhesive, invasive, phosphatase, lecithinase, DNA-ase, hemolytic activity) and genetic markers of pathogenicity of cnf-1. The etiologic role of bacteria of Klebsiella and an infecting (100, COE/dm3) dose emergence of acute intestinal infections (AII) is established. Detection of Klebsiella in water objects and especially in water of drinking appointment, in the absence of total coliform bacteria (TCB) contributes to the epidemic danger of water use. PMID:27430075

  7. [DISTRIBUTION OF BACTERIA OF THE KLEBSIELLA STRAIN IN WATER OBJECTS AND THEIR VALUE IN DEVELOPING OF THE WATER CAUSED ACUTE INTESTINAL INFECTIONS].

    PubMed

    Rakhmanin, Yu A; Ivanova, L V; Artyomova, T Z; Gipp, E K; Zagaynova, A V; Maksimkina, T N; Krasnyak, A V; Zhuravlev, P V; Aleshnya, V V; Panasovets, O P

    2016-01-01

    The wide circulation of Klebsiella bacteria in water ofwater objects of different climatic zones of Russia and various function is established. So bacteria of the Klebsiella strain are in superficial sources of the centralized water supply depending on extent of their biological and chemical pollution; underground waters at the unprotected water-bearing horizons; in drinking water at insufficiently effective system of its cleaning and disinfecting. Klebsiella circulating in water was shown to keep properties of pathogenicity and a virulence, possess resistance both to modern preparations and disinfecting agents (chlorine, an ultraviolet to radiation). Bacteria of the Klebsiella strain have high penetration in the water-bearing horizons. At strains of Klebsiella there is allocated considerable pathogenic potential (adhesive, invasive, phosphatase, lecithinase, DNA-ase, hemolytic activity) and genetic markers of pathogenicity of cnf-1. The etiologic role of bacteria of Klebsiella and an infecting (100, COE/dm3) dose emergence of acute intestinal infections (AII) is established. Detection of Klebsiella in water objects and especially in water of drinking appointment, in the absence of total coliform bacteria (TCB) contributes to the epidemic danger of water use.

  8. 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.

  9. Interleukin-1β sensitizes abdominal visceral afferents of cats to ischaemia and histamine

    PubMed Central

    Fu, Liang-Wu; Longhurst, John C

    1999-01-01

    Activation of abdominal splanchnic visceral afferents during mesenteric ischaemia induces visceral pain and evokes excitatory cardiovascular responses. Previous studies have shown that interleukin-1β (IL-1β) concentration is increased locally in tissues during ischaemia and reperfusion. Local administration of IL-1β sensitizes somatic afferents to mechanical, thermal and chemical stimulation. Therefore, we hypothesized that IL-1β stimulates or sensitizes splanchnic visceral afferents to ischaemia and to the action of chemical stimuli such as histamine. The concentration of IL-1β in mesenteric lymph and portal venous plasma in anaesthetized cats was measured with an enzyme-linked immunosorbent assay before, during and after 10 min of abdominal ischaemia. The level of IL-1β was significantly increased during ischaemia in lymph, but not in plasma. Discharge activity of single-unit abdominal visceral C fibre afferents was measured from the right thoracic sympathetic chain. Ischaemically sensitive C fibre afferents were identified according to their response to 5–10 min of abdominal ischaemia. Intra-arterial (i.a.) injection of a high dose of IL-1β (500 ng kg−1), but not of a lower dose (i.e. 15, 50 or 150 ng kg−1), stimulated most (six of seven) abdominal visceral afferents. IL-1β (15 ng kg−1, i.a.) significantly enhanced the increased activity of 11 of 13 C fibre afferents during 10 min of ischaemia. Conversely, an IL-1 type I receptor antagonist (IL-1ra, 1·5 μg kg−1, i.a.) significantly attenuated the increased activity in six of seven other C fibre afferents during ischaemia. IL-1β (15 ng kg−1, i.a.) significantly augmented the responses of 13 of 16 ischaemically sensitive abdominal afferents to histamine (5–10 μg kg−1, i.a.). Conversely, IL-1ra (1·5 μg kg−1, i.a.) significantly attenuated the responses of five of six other C fibre afferents to histamine. These data strongly suggest that stimulation of IL-1 type I receptors by IL-1

  10. B‐type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors

    PubMed Central

    Wong, K Y K; McSwiggan, S; Kennedy, N S J; MacWalter, R S; Struthers, A D

    2006-01-01

    Objective To test the hypothesis that B‐type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. Methods 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. Results In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r  =  −0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score − rest score; Spearman's r  =  0.28, two tailed p  =  0.049). In the cohort who did not have left ventricular systolic dysfunction (n  =  44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p  =  0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r  =  0.37 and −0.38, respectively). Conclusions BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death. PMID:16216865

  11. Acute gastro-intestinal illness and its association with hydroclimatic factors in British Columbia, Canada: A time-series analysis

    NASA Astrophysics Data System (ADS)

    Galway, L. P.; Allen, D. M.

    2013-12-01

    Rising global temperatures and expected shifts in regional hydroclimatology in a changing climate are likely to influence the risk of infectious waterborne illness. This study examines the role of hydroclimatology as an underlying driver of the epidemiology of waterborne gastro-intestinal illness and contributes to our currently limited understanding of the possible ecosystem-mediated impacts of climate change on health. Using time-series regression analysis, we examine the associations between three hydroclimatic factors (monthly temperature, precipitation, and streamflow) and the monthly occurrence of AGI illness in two communities in the province of British Columbia, Canada. The two communities were selected as study sites to represent the dominant hydroclimatic regimes that characterize the province of BC: the rainfall-dominated hydroclimatic regime and snowmelt-dominated hydroclimatic regime Our results show that the number of monthly cases of AGI increased with increasing temperature, precipitation, and streamflow in the same month in the context of a rainfall-dominated regime and with increasing streamflow in the previous month in the context of a snowfall-dominated regime. These results suggest that hydroclimatic factors play a role in driving the occurrence and variability of AGI illness in this setting. Further, this study has highlighted that the nature and magnitude of the effects of hydroclimatic factors on waterborne illness vary across different hydroclimatic settings. We conclude that the watershed may be an appropriate context within which we can and should enhance our understanding of water-related climate change impacts on health. Examining the role of hydroclimatology as an underlying driver of the epidemiology of infectious disease is key to understanding of the possible ecosystem-mediated impacts of climate change on health and developing appropriate adaptation responses.

  12. Incidence of forearm and hand ischaemia related to radial artery cannulation in newborn infants.

    PubMed

    Hack, W W; Vos, A; Okken, A

    1990-01-01

    We report the incidence of transient and permanent ischaemia of the forearm and hand caused by radial artery cannulation in a series of 98 newborn infants. Birth weight ranged from 550 to 3920 g (median 1600 g) and gestational age ranged from 26 to 40 weeks (median 31 weeks). In 4 of the 98 infants transient ischaemia of the forearm and/or hand occurred. In three infants the onset of ischaemia was probably related to thrombo-embolic events and in one infant to inadequate palmar collateral circulation. Permanent ischaemic damage with tissue loss did not occur in any infant. It is concluded that permanent ischaemic damage to the forearm and/or the hand with tissue loss, attributable to radial artery cannulation, is seldom encountered in newborn infants. In minimizing the risk of ischaemia, careful assessment of palmar collateral circulation prior to cannulation and of all factors predisposing to the onset of ischaemia is essential. Immediate removal of the catheter at the earliest signs of ischaemia, is essential to prevent ensuing tissue loss.

  13. [A rare etiology of acute occlusion of the small intestine: anisakiasis. Review of the literature apropos of a case].

    PubMed

    Morlier, D; Thiebault, S; Dalcher, G; Zeyer, B; Muller, J; Bader, R

    1989-05-01

    The authors report a case of acute small bowel occlusion related to anisakis. This parasitis is due to ingestion by man, an unusual host, of a nematode of "anisakis" type at larva stage, a parasite to be found in numerous species of raw or home-processed fish. The parasite whose symptomatology is aspecific, can be located on the whole digestive tube. Diagnosis suggested by medical inquiry along with eosinophily, can be confirmed by serology and discovery of the parasite after anatomo-pathologic analysis. Medical treatment consisting in associating anti-parasite medicines with corticoids in certain cases, is recommended in diffuse forms and allergic signs of disease. Surgical complications make the laparotomy necessary for appropriate diagnosis and curing of the patient. Increasing frequency of this pathology shows the importance of prophylactic measures such as: abstaining from raw or home-processed fish, cooking fish at a temperature of 60 degrees C, deep-freezing fish at a temperature of -20 degrees C for 24 h at least, before eating it raw. PMID:2673000

  14. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model

    PubMed Central

    Fan, Zhe; Jing, Huirong; Yao, Jihong; Li, Yang; Hu, Xiaowei; Shao, Huizhu; Shen, Gang; Pan, Jiyong; Luo, Fuwen; Tian, Xiaofeng

    2014-01-01

    Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway. PMID:25215173

  15. Intestinal Malrotation

    MedlinePlus

    ... the intestines don't position themselves normally during fetal development and aren't attached inside properly as a result. The exact reason this occurs is unknown. When a fetus develops in the womb, the intestines start out ...

  16. Intestinal ischemia in neonates and children

    PubMed Central

    JEICAN, IONUŢ ISAIA; ICHIM, GABRIELA; GHEBAN, DAN

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison’s disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis. PMID:27547054

  17. Intestinal ischemia in neonates and children.

    PubMed

    Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis. PMID:27547054

  18. Intestine Transplant

    MedlinePlus

    ... intestine segment, most intestine transplants involve a whole organ from a deceased donor. In addition, most intestine transplants are performed in ... blood before surgery. I am looking for ... allocation About UNOS Being a living donor Calculator - CPRA Calculator - KDPI Calculator - LAS Calculator - MELD ...

  19. Antithrombin up-regulates AMP-activated protein kinase signalling during myocardial ischaemia/reperfusion injury.

    PubMed

    Ma, Yina; Wang, Jinli; Gao, Junjie; Yang, Hui; Wang, Yanqing; Manithody, Chandrashekhara; Li, Ji; Rezaie, Alireza R

    2015-02-01

    Antithrombin (AT) is a protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to heparan sulfate proteoglycans (HSPGs) on vascular cells. AMP-activated protein kinase (AMPK) plays an important cardioprotective role during myocardial ischaemia and reperfusion (I/R). To determine whether the cardioprotective signaling function of AT is mediated through the AMPK pathway, we evaluated the cardioprotective activities of wild-type AT and its two derivatives, one having high affinity and the other no affinity for heparin, in an acute I/R injury model in C57BL/6J mice in which the left anterior descending coronary artery was occluded. The serpin derivatives were given 5 minutes before reperfusion. The results showed that AT-WT can activate AMPK in both in vivo and ex vivo conditions. Blocking AMPK activity abolished the cardioprotective function of AT against I/R injury. The AT derivative having high affinity for heparin was more effective in activating AMPK and in limiting infraction, but the derivative lacking affinity for heparin was inactive in eliciting AMPK-dependent cardioprotective activity. Activation of AMPK by AT inhibited the inflammatory c-Jun N-terminal protein kinase (JNK) pathway during I/R. Further studies revealed that the AMPK activity induced by AT also modulates cardiac substrate metabolism by increasing glucose oxidation but inhibiting fatty acid oxidation during I/R. These results suggest that AT binds to HSPGs on heart tissues to invoke a cardioprotective function by triggering cardiac AMPK activation, thereby attenuating JNK inflammatory signalling pathways and modulating substrate metabolism during I/R. PMID:25230600

  20. Mechanisms underlying presynaptic Ca2+ transient and vesicular glutamate release at a CNS nerve terminal during in vitro ischaemia

    PubMed Central

    Lee, Seul Yi; Kim, Jun Hee

    2015-01-01

    Key points Here we demonstrate presynaptic responses and mechanisms of increased vesicular glutamate release during in vitro ischaemia in the calyx of Held terminal, an experimentally accessible presynaptic terminal in the CNS. The ischaemia-induced increase in presynaptic Ca2+ was mediated by both Ca2+ influx and Ca2+-induced Ca2+ release from intracellular stores. The reverse operation of the plasma membrane Na+/Ca2+ exchanger (NCX) plays a key role in Ca2+ influx for triggering Ca2+ release from intracellular stores at presynaptic terminals during in vitro ischaemia. Ca2+ uptake via NCX underlies the ischaemia-induced Ca2+ rise and the consequent increase in vesicular glutamate release from presynaptic terminals in the early phase of brain ischaemia. Abstract An early consequence of brain ischaemia is an increase in vesicular glutamate release from presynaptic terminals. However, the mechanisms of this increased glutamate release are not fully understood. Here we studied presynaptic responses and mechanisms of increased glutamate release during in vitro ischaemia, using pre- and postsynaptic whole-cell recordings and presynaptic Ca2+ imaging at the calyx of Held synapse in rat brainstem slices. Consistent with results from other brain regions, in vitro ischaemia significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) without affecting their amplitude, suggesting that ischaemia enhances vesicular glutamate release from presynaptic terminals. We found that ischaemia-induced vesicular glutamate release was dependent on a rise in basal Ca2+ at presynaptic terminals, which resulted from extracellular Ca2+ influx and Ca2+ release from intracellular stores. During early ischaemia, increased Ca2+ influx into presynaptic terminals was due to reverse operation of the plasma membrane Na+/Ca2+ exchanger (NCX) rather than presynaptic depolarization or voltage-activated Ca2+ currents. KB-R7943, an inhibitor of NCX, prevented the

  1. Effects of adding fibrous feedstuffs to the diet of young pigs on growth performance, intestinal cytokines, and circulating acute phase proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of adding fibrous feedstuffs on growth performance, intestinal cytokine expression, markers of inflammation, abundance of phosphorylated S6 kinase (S6K), and the expression of genes that control intestinal growth was evaluated in weanling pigs. Pigs (n = 120; 5.2 kg and 24 d of age) wer...

  2. Proton-gated Ca(2+)-permeable TRP channels damage myelin in conditions mimicking ischaemia.

    PubMed

    Hamilton, Nicola B; Kolodziejczyk, Karolina; Kougioumtzidou, Eleni; Attwell, David

    2016-01-28

    The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca(2+)-dependent manner, abolishing action potential propagation. This has been attributed to glutamate release activating Ca(2+)-permeable N-methyl-D-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca(2+) concentration ([Ca(2+)]i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular [K(+)] and decrease of membrane K(+) conductance. Nevertheless, ischaemia raises oligodendrocyte [Ca(2+)]i, [Mg(2+)]i and [H(+)]i, and buffering intracellular pH reduces the [Ca(2+)]i and [Mg(2+)]i increases, showing that these are evoked by the rise of [H(+)]i. The H(+)-gated [Ca(2+)]i elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.

  3. Severe Raynaud's phenomenon-A streamlined approach to acute management.

    PubMed

    Lee, Regent; Lomas, Oliver; Handa, Ashok

    2011-01-01

    Raynaud's phenomenon is an exaggerated vasospastic response to cold or emotional stress which not only may cause the patient severe pain but also critical ischaemia and necrosis of the digits. We report the case of a 69-year-old woman who presented with rest pain, impending ulceration and necrosis of finger tips due to an episode of left-sided Raynaud's phenomenon. Intravenous prostacyclin was administered successfully as a bridge to endoscopic thoracic sympathectomy. Vascular surgery units are ideally positioned for the acute management of severe Raynaud's phenomenon to provide continuity of care to patients with profound digital ischaemia and impending tissue loss.

  4. Proliferating resident microglia after focal cerebral ischaemia in mice.

    PubMed

    Denes, Adam; Vidyasagar, Rishma; Feng, Jianghua; Narvainen, Johanna; McColl, Barry W; Kauppinen, Risto A; Allan, Stuart M

    2007-12-01

    Cerebral ischaemia usually results in the rapid death of neurons within the immediate territory of the affected artery. Neuronal loss is accompanied by a sequence of events, including brain oedema, blood-brain barrier (BBB) breakdown, and neuroinflammation, all of which contribute to further neuronal death. Although the role of macrophages and mononuclear phagocytes in the expansion of ischaemic injury has been widely studied, the relative contribution of these cells, either of exogenous or intrinsic central nervous system (CNS) origin is still not entirely clear. The purpose of this study, therefore, was to use different durations of transient middle cerebral artery occlusion (tMCAo) in the mouse to investigate fully post-occlusion BBB permeability and cellular changes in the brain during the 72 h post-MCAo period. This was achieved using in vivo magnetic resonance imaging (MRI) and cell labelling techniques. Our results show that BBB breakdown and formation of the primary ischaemic damage after tMCAo is not associated with significant infiltration of neutrophils, although more are observed with longer periods of MCAo. In addition, we observe very few infiltrating exogenous macrophages over a 72 h period after 30 or 60 mins of occlusion, instead a profound increase in proliferating resident microglia cells was observed. Interestingly, the more severe injury associated with 60 mins of MCAo leads to a markedly reduced proliferation of resident microglial cells, suggesting that these cells may play a protective function, possibly through phagocytosis of infiltrating neutrophils. These data further support possible beneficial actions of microglial cells in the injured brain.

  5. 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.

  6. Propofol improves recovery of the isolated working hypertrophic heart from ischaemia-reperfusion.

    PubMed

    King, Nicola; Al Shaama, Madj; Suleiman, M-Saadeh

    2012-11-01

    The general anaesthetic propofol shows promise in protecting normal hearts against various cardiac insults, but little is known about its cardioprotective potential in hypertrophic hearts. This study tested the hypothesis that propofol at a clinically relevant dose would enhance functional recovery in hypertrophic hearts following ischaemia. Hypertrophic hearts from spontaneously hypertensive rats and hearts from their normotensive controls, Wistar Kyoto Rats, were equilibrated in the working mode prior to global normothermic ischaemia. Reperfusion commenced with 10 min in Langendorff mode, followed by 30-min working reperfusion. Functional performance was measured throughout the working mode, whilst reperfusion damage was assessed from myocardial troponin I release during Langendorff reperfusion. Where used, 4 μg/ml propofol was added 10 min before ischaemia and was washed out 10 min into working reperfusion. An additional protocol investigated recovery of hearts protected by normothermic hyperkalaemic cardioplegic arrest. Following 20-min ischaemia, reperfusion damage was significantly worse in hypertrophic hearts compared to normal hearts, whilst addition of propofol to hypertrophic hearts significantly improved the aortic flow (31 ± 5.8 vs. 11.6 ± 2.0 ml/min, n = 6-7 ± SE, p < 0.05). Propofol also conferred significant protection following 30-min ischaemia where the recovery of cardiac output and stroke volume was similar to that for cardioplegia alone. Incubation with propofol improved the NADH/NAD(+) ratio in freshly isolated cardiomyocytes from hypertrophic hearts, suggesting possible improvements in metabolic flux. These findings suggest that propofol at the clinically relevant dose of 4 μg/ml is as effective as cardioplegic arrest in protecting hypertrophic hearts against ischaemia-reperfusion.

  7. Chronicity following ischaemia-reperfusion injury depends on tubular-macrophage crosstalk involving two tubular cell-derived CSF-1R activators: CSF-1 and IL-34.

    PubMed

    Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Ortiz, Alberto

    2016-09-01

    Two structurally unrelated ligands activate the macrophage colony stimulating factor receptor (CSF-1R, c-fms, CD115): M-CSF/CSF-1 and interleukin-34 (IL-34). Both ligands promote macrophage proliferation, survival and differentiation. IL-34 also activates the protein-tyrosine phosphatase ζ receptor (PTP-ζ, PTPRZ1). Both receptors and cytokines are increased during acute kidney injury. While tubular cell-derived CSF-1 is required for kidney repair, Baek et al (J Clin Invest 2015; 125: 3198-3214) have now identified tubular epithelial cell-derived IL-34 as a promoter of kidney neutrophil and macrophage infiltration and tubular cell destruction during experimental kidney ischaemia-reperfusion, leading to chronic injury. IL-34 promoted proliferation of both intrarenal macrophages and bone marrow cells, increasing circulating neutrophils and monocytes and their kidney recruitment. Thus, injured tubular cells release two CSF-1R activators, one (CSF-1) that promotes tubular cell survival and kidney repair and another (IL-34) that promotes chronic kidney damage. These results hold promise for the development of IL-34-targeting strategies to prevent ischaemia-reperfusion kidney injury in contexts such as kidney transplantation. However, careful consideration should be given to the recent characterization by Bezie et al. (J Clin Invest 2015; 125: 3952-3964) of IL-34 as a T regulatory cell (Treg) cytokine that modulates macrophage responses so that IL-34-primed macrophages potentiate the immune suppressive capacity of Tregs and promote graft tolerance. PMID:27190368

  8. Autonomic responses to exercise: cortical and subcortical responses during post-exercise ischaemia and muscle pain.

    PubMed

    Macefield, Vaughan G; Henderson, Luke A

    2015-03-01

    Sustained isometric contraction of skeletal muscle causes an increase in blood pressure, due to an increase in cardiac output and an increase in total peripheral resistance-brought about by an increase in sympathetically-mediated vasoconstriction. Both central command and reflex inputs from metaboreceptors in the contracting muscles have been shown to contribute to this sympathetically mediated increase in blood pressure. Occluding the blood supply and trapping the metabolites in the contracted muscle (post-exercise ischaemia) has shown that, while heart rate returns to baseline following exercise, the increase in MSNA and blood pressure persists in the absence of central command-sustained by peripheral inputs. Post-exercise ischaemia activates group III and IV muscle afferents, which are also activated during noxious stimulation. Indeed, post-exercise ischaemia is painful, so what is the role of pain in the increase in blood pressure? Intramuscular injection of hypertonic saline causes a deep dull ache, not unlike that produced by post-exercise ischaemia, and we have shown that this can cause a sustained increase in MSNA and blood pressure. We have used functional Magnetic Resonance Imaging (fMRI) of the brain to identify the cortical and subcortical sites involved in the sensory processing of muscle pain, and in the generation of the autonomic responses to muscle pain, produced either by post-exercise ischaemia or intramuscular injection of hypertonic saline. During static hand-grip exercise there were parallel increases in signal intensity in the contralateral primary motor cortex, deep cerebellar nuclei and cerebellar cortex that ceased at the end of the exercise, reflecting the start and end of central command. Progressive increases during the contraction phase occurred in the contralateral insula, as well as the contralateral primary somatosensory cortex, and continued during the period of post-exercise ischaemia. Decreases in signal intensity occurred in the

  9. Intestinal Epithelial TLR-4 Activation Is Required for the Development of Acute Lung Injury after Trauma/Hemorrhagic Shock via the Release of HMGB1 from the Gut.

    PubMed

    Sodhi, Chhinder P; Jia, Hongpeng; Yamaguchi, Yukihiro; Lu, Peng; Good, Misty; Egan, Charlotte; Ozolek, John; Zhu, Xiaorong; Billiar, Timothy R; Hackam, David J

    2015-05-15

    The mechanisms that lead to the development of remote lung injury after trauma remain unknown, although a central role for the gut in the induction of lung injury has been postulated. We hypothesized that the development of remote lung injury after trauma/hemorrhagic shock requires activation of TLR4 in the intestinal epithelium, and we sought to determine the mechanisms involved. We show that trauma/hemorrhagic shock caused lung injury in wild-type mice, but not in mice that lack TLR4 in the intestinal epithelium, confirming the importance of intestinal TLR4 activation in the process. Activation of intestinal TLR4 after trauma led to increased endoplasmic reticulum (ER) stress, enterocyte apoptosis, and the release of circulating HMGB1, whereas inhibition of ER stress attenuated apoptosis, reduced circulating HMGB1, and decreased lung injury severity. Neutralization of circulating HMGB1 led to reduced severity of lung injury after trauma, and mice that lack HMGB1 in the intestinal epithelium were protected from the development of lung injury, confirming the importance of the intestine as the source of HMGB1, whose release of HMGB1 induced a rapid protein kinase C ζ-mediated internalization of surface tight junctions in the pulmonary epithelium. Strikingly, the use of a novel small-molecule TLR4 inhibitor reduced intestinal ER stress, decreased circulating HMGB1, and preserved lung architecture after trauma. Thus, intestinal epithelial TLR4 activation leads to HMGB1 release from the gut and the development of lung injury, whereas strategies that block upstream TLR4 signaling may offer pulmonary protective strategies after trauma.

  10. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  11. 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…

  12. [Spinal cord ischaemia and preoperative clopidogrel withdrawal in an arteriosclerotic patient].

    PubMed

    Murat, O; Durand, E; Delépine, G; Nguyen, P; Malinovsky, J-M

    2008-04-01

    We report the case of a motor impairment associated with bladder dysfunction several days after clopidogrel withdrawal in an arteriosclerotic woman scheduled for thoracotomy under general and thoracic epidural anaesthesia. Even if spinal artery syndrome may have a lot of aetiologies, we believe in a direct link between clopidogrel withdrawal and medulla ischaemia. PMID:18378112

  13. Functional properties and responses to ischaemia-reperfusion in Langendorff perfused mouse heart.

    PubMed

    Headrick, J P; Peart, J; Hack, B; Flood, A; Matherne, G P

    2001-11-01

    Despite minimal model characterisation Langendorff perfused murine hearts are increasingly employed in cardiovascular research, and particularly in studies of myocardial ischaemia and reperfusion. Reported contractility remains poor and ischaemic recoveries variable. We characterised function in C57/BL6 mouse hearts using a ventricular balloon or apicobasal displacement and assessed responses to 10-30 min global ischaemia. We examined the functional effects of pacing, ventricular balloon design, perfusate filtration, [Ca(2+)] and temperature. Contractility was high in isovolumically functioning mouse hearts (measured as the change in pressure with time (+dP/dt), 6000-7000 mmHg s(-1)) and was optimal at a heart rate of approximately 420 beats min(-1), with the vasculature sub-maximally dilated, and the cellular energy state high. Post-ischaemic recovery (after 40 min reperfusion) was related to the ischaemic duration: developed pressure recovered by 82 +/- 5 %, 73 +/- 4 %, 68 +/- 3 %, 57 +/- 2 % and 41 +/- 5 % after 10, 15, 20, 25 and 30 min ischaemia, respectively. Ventricular compliance and elastance were both reduced post-ischaemia. Post-ischaemic recoveries were lower in the apicobasal model (80 +/- 4 %, 58 +/- 7 %, 40 +/- 3 %, 32 +/- 7 % and 25 +/- 5 %) despite greater reflow and lower metabolic rate (pre-ischaemic myocardial O(2) consumption (V(O2,myo)) 127 +/- 15 vs. 198 +/- 17 microl O(2) min(-1) g(-1)), contracture, enzyme and purine efflux. Electrical pacing slowed recovery in both models, small ventricular balloons (unpressurised volumes < 50-60 microl) artificially depressed ventricular function and recovery from ischaemia, and failure to filter the perfusion fluid to < 0.45 microm depressed pre- and post-ischaemic function. With attention to these various experimental factors, the buffer perfused isovolumically contracting mouse heart is shown to be stable and highly energized, and to possess a high level of contractility. The isovolumic model is more

  14. Increased gastric PCO2 during exercise is indicative of gastric ischaemia: a tonometric study

    PubMed Central

    Kolkman, J; Groeneveld, A; van der Berg, F G; Rauwerda, J; Meuwissen, S

    1999-01-01

    Background—Diagnosis of gastric ischaemia is difficult and angiography is an invasive procedure. Angiographic findings may not correlate with clinical importance. 
Aims—To investigate whether tonometric measurement of intragastric PCO2 during exercise can be used to detect clinically important gastric ischaemia. 
Methods—Fourteen patients with unexplained abdominal pain or weight loss were studied. Splanchnic angiography served as the gold standard. Three patients were studied again after a revascularisation procedure. Gastric PCO2 was measured from a nasogastric tonometer, with 10 minute dwell times, and after acid suppression. Gastric and capillary PCO2 were measured before, during, and after submaximal exercise of 10 minutes duration. 
Results—Seven patients had normal angiograms; seven had more than 50% stenosis in the coeliac (n=7) or superior mesenteric artery (n=4). Normal subjects showed no changes in tonometry. In patients with stenoses, the median intragastric PCO2 (PiCO2) at rest was 5.2 kPa (range 4.8-11.2) and rose to 6.4 kPa (range 5.7-15.7) at peak exercise; the median intragastric blood PCO2 gradient increased from 0.0 kPa (range −0.8 to 5.9) to 1.7 kPa (range 0.9 to 10.3; p<0.01). Only two subjects had abnormal tonometry at rest; all had supernormal values at peak exercise. The PCO2 gradient correlated with clinical and gastroscopic severity; in patients reexamined after revascularisation (n=3), exercise tonometry returned to normal. 
Conclusion—Gastric tonometry during exercise is a promising non-invasive tool for diagnosing and grading gastrointestinal ischaemia and evaluating the results of revascularisation surgery for symptomatic gastric ischaemia. 

 Keywords: gastric ischaemia; tonometry; carbon dioxide; exercise test PMID:9895373

  15. Mechanism and consequences of the shift in cardiac arginine metabolism following ischaemia and reperfusion in rats.

    PubMed

    Schreckenberg, Rolf; Weber, Pia; Cabrera-Fuentes, Hector A; Steinert, Isabel; Preissner, Klaus T; Bencsik, Péter; Sárközy, Márta; Csonka, Csaba; Ferdinandy, Péter; Schulz, Rainer; Schlüter, Klaus-Dieter

    2015-03-01

    Cardiac ischaemia and reperfusion leads to irreversible injury and subsequent tissue remodelling. Initial reperfusion seems to shift arginine metabolism from nitric oxide (NO) to polyamine formation. This may limit functional recovery at reperfusion. The hypothesis was tested whether ischaemia/reperfusion translates such a shift in arginine metabolism in a tumour necrosis factor (TNF)-α-dependent way and renin-angiotensin system (RAS)-dependent way into a sustained effect. Both, the early post-ischaemic recovery and molecular adaptation to ischaemia/reperfusion were analysed in saline perfused rat hearts undergoing global no-flow ischaemia and reperfusion. Local TNF-α activation was blocked by inhibition of TNF-α sheddase ADAM17. To interfere with RAS captopril was administered. Arginase was inhibited by administration of Nor-NOHA. Long-term effects of ischemia/reperfusion on arginine metabolism were analysed in vivo in rats receiving an established ischaemia/reperfusion protocol in the closed chest mode. mRNA expression analysis indicated a shift in the arginine metabolism from NO formation to polyamine metabolism starting within 2 hours (h) of reperfusion and translated into protein expression within 24 h. Inhibition of the TNF-α pathway and captopril attenuated these delayed effects on post-ischaemic recovery. This shift in arginine metabolism was associated with functional impairment of hearts within 24 h. Inhibition of arginase but not that of TNF-α and RAS pathways improved functional recovery immediately. However, no benefit was observed after four months. In conclusion, this study identified TNF-α and RAS to be responsible for depressed cardiac function that occurred a few hours after reperfusion. PMID:25502809

  16. Donor brain death leads to differential immune activation in solid organs but does not accelerate ischaemia-reperfusion injury.

    PubMed

    Ritschl, Paul Viktor; Ashraf, Muhammad Imtiaz; Oberhuber, Rupert; Mellitzer, Vanessa; Fabritius, Cornelia; Resch, Thomas; Ebner, Susanne; Sauter, Martina; Klingel, Karin; Pratschke, Johann; Kotsch, Katja

    2016-05-01

    A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia-reperfusion injury (IRI) post-transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3(+) CD4(+) , CD3(+) CD8(+) T cells and NKp46(+) NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post-transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham-transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx.

  17. Chronic Administration of Δ9-Tetrahydrocannabinol Induces Intestinal Anti-Inflammatory MicroRNA Expression during Acute Simian Immunodeficiency Virus Infection of Rhesus Macaques

    PubMed Central

    Chandra, Lawrance C.; Kumar, Vinay; Torben, Workineh; Stouwe, Curtis Vande; Winsauer, Peter; Amedee, Angela; Molina, Patricia E.

    2014-01-01

    ABSTRACT Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression. Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques. To determine if the anti-inflammatory effects of Δ9-THC involved differential microRNA (miRNA) modulation, we profiled miRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the intestine of uninfected macaques receiving Δ9-THC (n = 3) and SIV-infected macaques administered either vehicle (VEH/SIV; n = 4) or THC (THC/SIV; n = 4). Chronic Δ9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days p.i. At 60 days p.i., ∼28% of miRNAs showed decreased expression in the VEH/SIV group compared to none showing decrease in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187, previously been shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator, was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV macaques compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. These results support a role for differential miRNA induction in THC-mediated suppression of intestinal

  18. Intestinal steroidogenesis.

    PubMed

    Bouguen, Guillaume; Dubuquoy, Laurent; Desreumaux, Pierre; Brunner, Thomas; Bertin, Benjamin

    2015-11-01

    Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of steroidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor-1 (SF-1) but a closely related homolog, namely the liver receptor homolog-1 (LRH-1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel diseases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions.

  19. The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice

    PubMed Central

    Heimesaat, Markus M.; Alutis, Marie; Grundmann, Ursula; Fischer, André; Tegtmeyer, Nicole; Böhm, Manja; Kühl, Anja A.; Göbel, Ulf B.; Backert, Steffen; Bereswill, Stefan

    2014-01-01

    Campylobacter jejuni infections have a high prevalence worldwide and represent a significant socioeconomic burden. C. jejuni can cross the intestinal epithelial barrier as visualized in biopsies derived from human patients and animal models, however, the underlying molecular mechanisms and associated immunopathology are still not well understood. We have recently shown that the secreted serine protease HtrA (high temperature requirement A) plays a key role in C. jejuni cellular invasion and transmigration across polarized epithelial cells in vitro. In the present in vivo study we investigated the role of HtrA during C. jejuni infection of mice. We used the gnotobiotic IL-10−/− mouse model to study campylobacteriosis following peroral infection with the C. jejuni wild-type (WT) strain NCTC11168 and the isogenic, non-polar NCTC11168ΔhtrA deletion mutant. Six days post infection (p.i.) with either strain mice harbored comparable intestinal C. jejuni loads, whereas ulcerative enterocolitis was less pronounced in mice infected with the ΔhtrA mutant strain. Moreover, ΔhtrA mutant infected mice displayed lower apoptotic cell numbers in the large intestinal mucosa, less colonic accumulation of neutrophils, macrophages and monocytes, lower large intestinal nitric oxide, IFN-γ, and IL-6 as well as lower TNF-α and IL-6 serum concentrations as compared to WT strain infected mice at day 6 p.i. Notably, immunopathological responses were not restricted to the intestinal tract given that liver and kidneys exhibited mild histopathological changes 6 days p.i. with either C. jejuni strain. We also found that hepatic and renal nitric oxide levels or renal TNF-α concentrations were lower in the ΔhtrA mutant as compared to WT strain infected mice. In conclusion, we show here that the C. jejuni HtrA protein plays a pivotal role in inducing host cell apoptosis and immunopathology during murine campylobacteriosis in the gut in vivo. PMID:24959425

  20. Intestinal obstruction

    MedlinePlus

    ... of the bowel may be due to: A mechanical cause, which means something is in the way ... lung disease Use of certain medicines, especially narcotics Mechanical causes of intestinal obstruction may include: Adhesions or ...

  1. Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans.

    PubMed

    Xia, Z; Li, H; Irwin, M G

    2016-09-01

    Myocardial ischaemia reperfusion injury is the leading cause of death in patients with cardiovascular disease. Interventions such as ischaemic pre and postconditioning protect against myocardial ischaemia reperfusion injury. Certain anaesthesia drugs and opioids can produce the same effects, which led to an initial flurry of excitement given the extensive use of these drugs in surgery. The underlying mechanisms have since been extensively studied in experimental animal models but attempts to translate these findings to clinical settings have resulted in contradictory results. There are a number of reasons for this such as dose response, the intensity of the ischaemic stimulus applied, the duration of ischaemia and lost or diminished cardioprotection in common co-morbidities such as diabetes and senescence. This review focuses on current knowledge regarding myocardial ischaemia reperfusion injury and cardioprotective interventions both in experimental animal studies and in clinical trials. PMID:27566808

  2. Effect of caffeic acid phenethyl ester on survival of axial pattern flaps in rats with ischaemia-reperfusion injuries.

    PubMed

    Bilen, Bilge Türk; Kilinç, Hidir; Alaybeyoglu, Nezih; Celik, Mehmet; Iraz, Mustafa; Sezgin, Nurzen; Gültek, Ahmet

    2006-01-01

    Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.

  3. Ischaemia-induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

    PubMed Central

    Aupetit, Jean-François; Loufoua-Moundanga, Joseph; Faucon, Georges; Timour, Quadiri

    1997-01-01

    In the last decade, a number of clinical observations have questioned the efficacy of certain class I antiarrhythmic drugs against ischaemia-induced ventricular fibrillation. The effects of three drugs of this class, disopyramide (Ia), lignocaine (Ib) and flecainide (Ic) on the vulnerability to fibrillation during experimental ischaemia were investigated.The study was carried out in anaesthetized, open-chest pigs (n=8 for each of the drugs, in addition to the control group, n=6). Vulnerability to fibrillation was evaluated by measuring electrical fibrillation threshold (EFT) by means of stepwise increased intensity of wide (100 ms) diastolic impulses applied to the ischaemic tissue at a 180 beats min−1 rate. Monophasic action potential (MAP) duration and conduction time in the ischaemic region were also measured.EFT determinations were performed before and during periods of ischaemia induced by complete occlusion of the left anterior descending coronary artery near its origin. Ischaemic periods of increasing duration (30, 60, 90, 120, 150 s) were induced to determine the electrophysiological changes, of EFT especially, leading to fibrillation.In the absence of ischaemia, all three drugs, administered by intravenous route (1 mg kg−1 plus 0.04 mg kg−1 min−1) increased EFT to a similar extent (from approximately 7 to 10 mA), despite a 25% prolongation of conduction time.During ischaemia, none of the drugs prevented the fall in EFT towards 0 mA, resulting in spontaneous fibrillation. After 30 s of ischaemia, they no longer had any capacity for raising EFT and, after 60, 90 and 120 s of ischaemia, the decrease in EFT was exacerbated. This accelerated reduction in EFT shortened the time to onset of fibrillation (after 120 s of ischaemia, 62.5% of fibrillations with flecainide instead of 12.5 under control conditions, 75% instead of 25 with lignocaine and 50% instead of 25 with disopyramide). The reduction in MAP duration due to

  4. 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

  5. Simultaneous study of haemodynamic, metabolic and behavioural sequelae in a model of cerebral ischaemia in aged rats: effects of nicergoline.

    PubMed

    Le Poncin-Lafitte, M; Grosdemouge, C; Duterte, D; Rapin, J R

    1984-01-01

    Unilateral cerebral ischaemia was induced in 18-month-old Long-Evans rats by injection of 2,000 labelled microspheres (phi 50 microns) into the carotid blood stream. This results in an ipsilateral decrease in cerebral blood flow, development of severe oedema and modifications of glucose uptake and consumption. Furthermore, this ischaemia led to a deterioration of the avoidance response in conditioned animals. All these disturbances, including the cerebral oedema, diminished with nicergoline pretreatment. PMID:6706123

  6. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier.

    PubMed

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-07-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis.

  7. Augmented myocardial ischaemia by nicotine – Mechanisms and their possible significance

    PubMed Central

    Schrör, Karsten; Zimmermann, Katja C; Tannhäuser, Roman

    1998-01-01

    To study the effect of nicotine on the severity of experimental myocardial ischaemia, Langendorff hearts of rabbits (n=7–12 per group) were subjected to 2 h of low-flow ischaemia followed by 1 h of reperfusion. Infusion of nicotine (100 ng ml−1) caused only minor changes in non-ischaemic conditions but a significant (P<0.05) increase in end-diastolic pressure (LVEDP), loss of creatine kinase (CK) and troponin (TnT) as well as increase in noradrenaline (NA) overflow in reperfused ischaemic hearts. RT–PCR was done on total RNA for mRNA expression of the constitutive (COX-1) and inducible cyclooxygenase (COX-2). There was no COX-2 in non-ischaemic hearts but a significant expression in ischaemia (n=5) which was further increased by nicotine. These data were confirmed at the protein level by Western blotting and additionally shown that COX-1 remained unchanged. There was a marked increase in prostacyclin (PGI2) and a 2 fold increase in NA overflow which were both stimulated by nicotine. The aggravating effects of nicotine on myocardial ischaemia (CK release) as well as the expression of COX-2 mRNA were prevented by pretreatment with the β-blocker pindolol (1 μM). The data demonstrate marked deleterious actions of nicotine in reperfused ischaemic hearts. These actions are probably related to the increase in catecholamine overflow, are β-receptor-mediated and involve enhanced gene expression of COX-2. PMID:9776347

  8. Therapeutic Effects of Policosanol and Atorvastatin against Global Brain Ischaemia-Reperfusion Injury in Gerbils

    PubMed Central

    Molina, V.; Ravelo, Y.; Noa, M.; Mas, R.; Pérez, Y.; Oyarzábal, A.; Mendoza, N.; Valle, M.; Jiménez, S.; Sánchez, J.

    2013-01-01

    Stroke is the third cause of death and the first of permanent adult disability. Pretreatment with policosanol and atorvastatin has been effective in experimental models of cerebral ischaemia in rodents. The objective was to compare the therapeutic effects of policosanol and atorvastatin in a model of global cerebral ischaemia in gerbils. Gerbils were distributed into seven groups, a negative control and six with ischaemia-reperfusion-induced global cerebral ischemia (one vehicle positive control, two policosanol (100 and 200 mg/kg), two atorvastatin (10 and 20 mg/kg) and one aspirin (60 mg/kg) group). Treatments were given 4 h after ischaemia induction. Effects on ischemia-reperfusion-induced symptoms, hyperlocomotion, damage of pyramidal hipoccampal neurons and increased plasma oxidative markers were investigated. Positive, not negative controls, exhibited clinical symptoms, hyperlocomotion, neuronal damage and increased plasma oxidative markers. Policosanol (100 and 200 mg/kg) reduced significantly ischemia-reperfusion-induced symptoms, the frequency of symptomatic animals, histological scores of neuronal damage and plasma oxidative markers as compared with the positive control group. Atorvastatin (10 and 20 mg/kg) decreased significantly the symptoms and histological scores, but unchanged the frequency of symptomatic gerbils and oxidative variables. Only the highest dose of policosanol (200 mg/kg) and atorvastatin (20 mg/kg) reduced significantly ischemia reperfusion-induced hyperlocomotion, policosanol being the most effective. Aspirin 60 mg/kg lowered significantly symptom score, the rate of symptomatic gerbils and hyperlocomotion versus the positive controls, but failed to modify oxidative parameters. In conclusion, postreperfusion treatment with policosanol and atorvastatin was effective for ameliorating symptoms, hyperlocomotion and neurological damage of hippocampal CA1 neurons in gerbils with ischemia-reperfusion-induced global cerebral ischemia, but only

  9. Pathological yawning as a presenting symptom of brain stem ischaemia in two patients

    PubMed Central

    Cattaneo, L; Cucurachi, L; Chierici, E; Pavesi, G

    2006-01-01

    Two cases of brain stem stroke involving the upper pons and the ponto‐mesencephalic junction presented with transient excessive pathological yawning, associated with gait ataxia and in one subject with upper limb and facial hemiparesis. A causal relation is hypothesised between the brain stem lesion and pathological yawning, possibly related to denervation hypersensitivity of a putative brain stem yawn centre. Excessive yawning may herald brain stem ischaemia. PMID:16174652

  10. A finite volume method solution for the bidomain equations and their application to modelling cardiac ischaemia.

    PubMed

    Johnston, Peter R

    2010-01-01

    This paper presents an implementation of the finite volume method with the aim of studying subendocardial ischaemia during the ST segment. In this implementation, based on hexahedral finite volumes, each quadrilateral sub-face is split into two triangles to improve the accuracy of the numerical integration in complex geometries and when fibre rotation is included. The numerical method is validated against previously published solutions obtained from slab and cylindrical models of the left ventricle with subendocardial ischaemia and no fibre rotation. Epicardial potential distributions are then obtained for a half-ellipsoid model of the left ventricle. In this case it is shown that for isotropic cardiac tissue the degree of subendocardial ischaemia does not affect the epicardial potential distribution, which is consistent with previous findings from analytical studies in simpler geometries. The paper also considers the behaviour of various preconditioners for solving numerically the resulting system of algebraic equations resulting from the implementation of the finite volume method. It is observed that each geometry considered has its own optimal preconditioner.

  11. Protective effects of a plant histaminase in myocardial ischaemia and reperfusion injury in vivo.

    PubMed

    Masini, Emanuela; Pierpaoli, Simone; Marzocca, Cosimo; Mannaioni, Pier Francesco; Pietrangeli, Paola; Mateescu, Mircea Alexandru; Zelli, Massimo; Federico, Rodolfo; Mondovì, Bruno

    2003-09-19

    Grass pea seedling histaminase (a copper-diamine oxidase) was found to exert a significant cardioprotection against post-ischaemic reperfusion damage. Electrocardiogram (ECG) recordings from the rats subjected in vivo to ischaemia and reperfusion showed ventricular tachycardia (VT) and ventricular fibrillations (VF) occurring in 9 out of 12 untreated rats whereas no ventricular arrhythmias were found under histaminase (80U/kg body weight) treatment (n=16 rats). Computer-assisted morphometry of the ischaemic reperfused hearts stained with nitroblue tetrazolium showed the extension of damaged myocardium (area at risk and infarct size) significantly reduced in rats treated with histaminase, in comparison with the non-treated rats, whereas no protection was found with the semicarbazide inactivated histaminase. Biochemical markers of ischaemia-reperfusion myocardial tissue damage: malonyldialdehyde (MDA), tissue calcium concentration, myeloperoxidase (MPO), and apoptosis indicator caspase-3 were significantly elevated in untreated post-ischaemic reperfused rats, but significantly reduced under histaminase protection. In conclusion, plant histaminase appears to protect hearts from ischaemia-reperfusion injury by more than one mechanism, essentially involving histamine oxidation, and possibly as reactive oxygen species scavenger, presenting good perspectives for a novel therapeutic approach in treatment of ischaemic heart pathology. PMID:12951068

  12. Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice

    PubMed Central

    Watanabe, Satoru; Chan, Kitti Wing Ki; Wang, Jiaqi; Rivino, Laura; Lok, Shee-Mei

    2015-01-01

    ABSTRACT Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue viral load and cytokine production, which can be suppressed by anti-tumor necrosis factor alpha (anti-TNF-α) Abs. Flow cytometric analysis identified increased infection in CD11bint CD11cint/hi CD103− antigen-presenting cells by IC inoculation, suggesting that these infected cells may be responsible for the increase in TNF-α production and vascular permeability in the small intestine that lead to mortality in mice. Our findings may have important implications for the development of dengue therapeutics. IMPORTANCE We examined the relationship between the neutralizing level of Abs at the time of infection and subsequent disease progression in a mouse model in order to understand why patients who are shown to have a neutralizing

  13. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier

    PubMed Central

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-01-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425] PMID:25936779

  14. Intestinal Obstruction

    MedlinePlus

    ... the small intestine (duodenum) may be caused by cancer of the pancreas, scarring from an ulcer, or Crohn disease . Rarely, a gallstone, a mass of undigested food, or a collection of parasitic worms may block ... commonly caused by cancer, diverticulitis , or a hard lump of stool (fecal ...

  15. Peri-infarct ischaemia assessed by cardiovascular MRI: comparison with quantitative perfusion single photon emission CT imaging

    PubMed Central

    Cochet, H; Bullier, E; Ragot, C; Gilbert, S H; Pucheu, Y; Laurent, F; Coste, P; Bordenave, L; Montaudon, M

    2014-01-01

    Objective: To develop a new method for the cardiac MR (CMR) quantification of peri-infarct ischaemia using fused perfusion and delayed–enhanced images and to evaluate this method using quantitative single photon emission CT (SPECT) imaging as a reference. Methods: 40 patients presenting with peri-infarct ischaemia on a routine stress 99mTc-SPECT imaging were recruited. Within 8 days of the SPECT study, myocardial perfusion was evaluated using stress adenosine CMR. Using fused perfusion and delayed–enhanced images, peri-infarct ischaemia was quantified as the percentage of myocardium with stress-induced perfusion defect that was adjacent to and larger than a scar. This parameter was compared with both the percent myocardium ischaemia (SD%) and the ischaemic total perfusion deficit (TPD). The diagnostic performance of CMR in detection of significant coronary artery stenosis (of ≥70%) was also determined. Results: On SPECT imaging, in addition to peri-infarct ischaemia, reversible perfusion abnormalities were detected in a remote zone in seven patients. In the 33 patients presenting with only peri-infarct ischaemia, the agreement between CMR peri-infarct ischaemia and both SD% and ischaemic TPD was excellent [intraclass coefficient of correlation (ICC) = 0.969 and ICC = 0.877, respectively]. CMR-defined peri-infarct ischaemia for the detection of a significant coronary artery stenosis showed an areas under receiver–operating characteristic curve of 0.856 (95% confidence interval, 0.680–0.939). The best cut-off value was 8.1% and allowed a 72% sensitivity, 96% specificity, 60% negative predictive value and 97% positive predictive value. Conclusion: This proof-of-concept study shows that CMR imaging has the potential as a test for quantification of peri-infarct ischaemia. Advances in knowledge: This study demonstrates the proof of concept of a commonly known intuitive idea, that is, evaluating the peri-infarct ischaemic burden by subtracting delayed

  16. Balancing ischaemia and bleeding risks with novel oral anticoagulants.

    PubMed

    Baber, Usman; Mastoris, Ioannis; Mehran, Roxana

    2014-12-01

    Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention. PMID:25367652

  17. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium.

    PubMed

    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

    2008-08-01

    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

  18. Faster clearance of omeprazole in rats with acute renal failure induced by uranyl nitrate: contribution of increased expression of hepatic cytochrome P450 (CYP) 3A1 and intestinal CYP1A and 3A subfamilies.

    PubMed

    Lee, Dae Y; Jung, Young S; Shin, Hyun S; Lee, Inchul; Kim, Young C; Lee, Myung G

    2008-07-01

    It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg(-1)) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 microg min mL(-1)), possibly due to the significantly faster non-renal clearance (56.6 vs 41.2 mL min(-1) kg(-1)) compared with control rats. This could have been due to increased expression of hepatic CYP3A1 in U-ARF rats. After oral administration of omeprazole (40 mgkg(-1)) to U-ARF rats, the AUC was also significantly reduced (89.3 vs 235 microg min mL(-1)) compared with control rats. The AUC difference after oral administration (62.0% decrease) was greater than that after intravenous administration (24.9% decrease). This may have been primarily due to increased intestinal metabolism of omeprazole caused by increased expression of intestinal CYP1A and 3A subfamilies in U-ARF rats, in addition to increased hepatic metabolism.

  19. Experiment-model interaction for analysis of epicardial activation during human ventricular fibrillation with global myocardial ischaemia.

    PubMed

    Clayton, R H; Nash, M P; Bradley, C P; Panfilov, A V; Paterson, D J; Taggart, P

    2011-10-01

    We describe a combined experiment-modelling framework to investigate the effects of ischaemia on the organisation of ventricular fibrillation in the human heart. In a series of experimental studies epicardial activity was recorded from 10 patients undergoing routine cardiac surgery. Ventricular fibrillation was induced by burst pacing, and recording continued during 2.5 min of global cardiac ischaemia followed by 30 s of coronary reflow. Modelling used a 2D description of human ventricular tissue. Global cardiac ischaemia was simulated by (i) decreased intracellular ATP concentration and subsequent activation of an ATP sensitive K⁺ current, (ii) elevated extracellular K⁺ concentration, and (iii) acidosis resulting in reduced magnitude of the L-type Ca²⁺ current I(Ca,L). Simulated ischaemia acted to shorten action potential duration, reduce conduction velocity, increase effective refractory period, and flatten restitution. In the model, these effects resulted in slower re-entrant activity that was qualitatively consistent with our observations in the human heart. However, the flattening of restitution also resulted in the collapse of many re-entrant waves to several stable re-entrant waves, which was different to the overall trend we observed in the experimental data. These findings highlight a potential role for other factors, such as structural or functional heterogeneity in sustaining wavebreak during human ventricular fibrillation with global myocardial ischaemia.

  20. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  1. Intestinal spirochaetosis

    PubMed Central

    Lee, F. D.; Kraszewski, A.; Gordon, J.; Howie, J. G. R.; McSeveney, D.; Harland, W. A.

    1971-01-01

    An abnormal condition of the large intestine is described in which the surface epithelium is infested by short spirochaetes. Diagnosis can be made by light microscopy. A review of 14 cases diagnosed by rectal biopsy and 62 cases involving the appendix shows no consistent symptom complex. The possible significance is discussed. ImagesFig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 1 PMID:5548558

  2. Ischaemic Markers in Acute Hepatic Injury

    PubMed Central

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  3. Small intestinal ischemia and infarction

    MedlinePlus

    ... small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine ... Embolus: Blood clots can block one of the arteries supplying the intestine. People who have had a ...

  4. Intestinal Transplant Inflammation: the Third Inflammatory Bowel Disease.

    PubMed

    Kroemer, Alexander; Cosentino, Christopher; Kaiser, Jason; Matsumoto, Cal S; Fishbein, Thomas M

    2016-11-01

    Intestinal transplantation is the most immunologically complex of all abdominal organ transplants. Understanding the role both humoral and innate and adaptive cellular immunity play in intestinal transplantation is critical to improving outcomes and increasing indications for patients suffering from intestinal failure. Recent findings highlighting the impact of donor-specific antibodies on intestinal allografts, the role of NOD2 as a key regulator of intestinal immunity, the protective effects of innate lymphoid cells, and the role of Th17 in acute cellular rejection are reviewed here. PMID:27645751

  5. Intestinal Transplant Inflammation: the Third Inflammatory Bowel Disease.

    PubMed

    Kroemer, Alexander; Cosentino, Christopher; Kaiser, Jason; Matsumoto, Cal S; Fishbein, Thomas M

    2016-11-01

    Intestinal transplantation is the most immunologically complex of all abdominal organ transplants. Understanding the role both humoral and innate and adaptive cellular immunity play in intestinal transplantation is critical to improving outcomes and increasing indications for patients suffering from intestinal failure. Recent findings highlighting the impact of donor-specific antibodies on intestinal allografts, the role of NOD2 as a key regulator of intestinal immunity, the protective effects of innate lymphoid cells, and the role of Th17 in acute cellular rejection are reviewed here.

  6. [Persistent psychotic disorder following bilateral mesencephalo-thalamic ischaemia: case report].

    PubMed

    Predescu, A; Damsa, C; Riegert, M; Bumb, A; Pull, C

    2004-01-01

    A 38-year old male patient with no history of psychiatric illness developed a progressive psychotic disorder after bilateral (predominantly left) mesencephalo-thalamic cerebral ischaemia. The reason of the emergency hospitalization was the sudden onset of a confusional state, culminating in a fluctuating comatose status. The neurological examination found mild right hemiparesia, praxic disorders and reactive left mydriasis with paresia of the downward vertical stare, leading to the hospitalisation in the neurology department for suspicion of a cerebral vascular ischaemic accident. The psychiatric symptoms started with acoustic-verbal hallucinations, poorly structured paranoid delusions, progressively developed over two weeks, followed by behavioural disorders with psychomotor agitation and heteroaggressivity. The patient was transferred to the psychiatric department, because of the heteroaggressive risk and lack of morbid consciousness, in spite of recovering from the confusional status. An intensive psychiatric management was proposed, combining a psychotherapeutic approach with 4 mg of risperidone and adjustable doses of benzodiazepine according to the psychomotor agitation. During the next days, there was a net recovery of the behavioural disorders, in spite of the persistence of the ideas of persecution. All the neurological symptoms also decreased. An anomaly of the polygon of Willis was found on a cerebral arteriography (the posterior cerebral arteries had a foetal origin, dependent on carotidal axes and not on the vertebro-basilar system). The main emboligen risk factor was the presence of a permeable foramen ovale, discovered during a transoesophageal echography. The patient underwent a surgical correction of the permeable foramen ovale. The psychiatric hospitalization for three months was continued by ambulatory follow-up. The initial positive symptoms (delusions, acoustic-verbal hallucinations) progressively diminished while negative symptoms became

  7. The inhibitory effect of bevantolol on the accumulation of non-esterified fatty acids during ischaemia in the dog heart in situ.

    PubMed

    Miura, I; Nasa, Y; Ichihara, K; Abiko, Y

    1991-04-01

    1. The left anterior descending coronary artery (LAD) was completely ligated for 90 min (i.e. myocardial ischaemia was produced) in the dog anaesthetized with pentobarbital. 2. Bevantolol, a beta 1-adrenoceptor antagonist, was injected (1 mg/kg, intravenously) 5 min before LAD occlusion. The bevantolol injection decreased heart rate without affecting blood pressure. 3. The myocardial samples were taken from the LAD area immediately after the end of LAD occlusion, and were subjected to analysis of the myocardial levels of non-esterified fatty acids (NEFA). 4. In dogs in which saline was injected, ischaemia produced accumulation of NEFA, especially arachidonic and palmitoleic acids, in the myocardium. 5. In dogs in which bevantolol was injected, the accumulation of NEFA induced by ischaemia was almost completely inhibited. 6. It is concluded that bevantolol inhibits ischaemia-induced accumulation of NEFA in the myocardium, and that stimulation of the beta 1-adrenoceptors is probably responsible for NEFA accumulation induced by ischaemia.

  8. A colonic duplication cyst causing bowel ischaemia in a 74-year-old lady

    PubMed Central

    Fenelon, Christopher; Boland, Michael R; Kenny, Brian; Faul, Peter; Tormey, Shona

    2016-01-01

    Colonic duplication cysts are rare congenital malformations that predominantly present before the age of 2 years. We report the case of a 74-year-old lady who presented with sudden onset abdominal pain. A computed tomography scan noted a calcified structure adjacent to abnormal loops of bowel. Intraoperative findings revealed an ischaemic loop of small bowel wrapped around a mass in the mesentery adjacent to the sigmoid colon. Final histology revealed a colonic duplication cyst. Colonic duplication cysts are rare entities that most commonly cause obstruction or perforation. We present the very rare case of a colonic duplication cyst causing bowel ischaemia in an elderly female. PMID:27572680

  9. Effects of naftidrofuryl on cerebral hemodynamics, metabolism and function after a retracted ischaemia.

    PubMed

    Le Poncin-Lafitte, M; Grosdemouge, C; Roy-Billon, C; Duterte, D; Rapin, J R

    1982-12-01

    Unilateral microemboli were formed in the brains of Long Evans rats by means of an intracarotid injection of microspheres (50 mu). This embolization resulted in a decrease in blood flow, severe cerebral oedema and a modification of glucose uptake. Furthermore, these microemboli affected a conditioned avoidance response. Naftidrofuryl enabled a better recovery of the processes involved in the expression of acquisition. This has been related to a decrease in the development of oedema on one side and to a better glucose uptake on the other. These data demonstrated that naftidrofuryl influences the sequelae of rapidly regressive ischaemia. PMID:7165427

  10. Endovascular repair of spontaneous infrarenal aortic dissection presenting as severe lower extremity ischaemia.

    PubMed

    Adam, D J; Roy-Choudhury, S; Bradbury, A W

    2007-12-01

    We report a 90-year old man who presented with severe lower extremity ischaemia due to spontaneous dissection of a non-aneurysmal infrarenal abdominal aorta. The aortic lesion was treated using an aorto-uni-iliac stent-graft with contralateral common iliac artery occlusion and femoro-femoral cross-over bypass. The patient underwent digital amputation and debridement of the foot four weeks post-operatively. At 12 months follow-up, he remains symptom-free with an excluded dissection, patent reconstruction and healed foot.

  11. Pronounced alterations in T-wave morphology during dipyridamole-induced ischaemia.

    PubMed

    Ferrando-Castagnetto, F; Ricca-Mallada, R; Ferrando-Castagnetto, R

    2016-01-01

    The case describes a 77-year-old woman with multivessel coronary disease exhibiting marked changes of T-wave morphology induced by dipyridamole, an unusual finding in which the diagnostic accuracy in this clinical context is uncertain. Gated-SPECT imaging demonstrated severe ischaemia extending through inferior and posterolateral regions of the left ventricle with normal motility and contractile function in response to vasodilator stress. Possible underlying mechanisms and clinical implications of observed electrocardiographic changes are discussed. T-loop modifications during vasodilator stress SPECT and correlation of these changes with the amount of ischaemic injury need further evaluation.

  12. Neuroprotective properties of lifarizine compared with those of other agents in a mouse model of focal cerebral ischaemia.

    PubMed Central

    Brown, C. M.; Calder, C.; Linton, C.; Small, C.; Kenny, B. A.; Spedding, M.; Patmore, L.

    1995-01-01

    1. Changes in the peripheral type benzodiazepine binding site density following middle cerebral artery occlusion in the mouse, have been used as a marker of neuronal damage. These sites can be identified using the selective ligand [3H]-PK 11195 located on non neuronal cells, macrophages and astroglia, within the CNS. Glial cell proliferation and macrophage invasion is an unvoidable sequelae to cerebral ischaemic injury, secondary to neuronal loss. Following occlusion of the left middle cerebral artery (left MCA) a reproducible lesion was found in the parietal cortex within 7 days which gave rise to a significant increase in [3H]-PK 11195 binding. 2. Treatment of animals with the sodium channel blocker, lifarizine, significantly reduced the ischaemia-induced increase in [3H]-PK 11195 binding when given either 30 min pre-ischaemia and three times daily for 7 days at 0.5 mg kg-1, i.p. (P < 0.01) or delayed until 15 min post-ischaemia and three times daily for 7 days at 0.5 mg kg-1, i.p. (P < 0.001). Lifarizine was an effective neuroprotective agent in this model of focal ischaemia in the mouse. 3. Lifarizine also showed a dose-related protection against the ischaemia-induced increase in [3H]-PK 11195 binding with significant protection at doses of 0.1 mg kg-1, i.p. (P < 0.05), 0.25 mg kg-1, i.p. (P < 0.01) or 0.5 mg kg-1, i.p. (P < 0.01) 15 min post-ischaemia and b.i.d. for 7 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8564201

  13. Nasogastric tube syndrome induced by an indwelling long intestinal tube

    PubMed Central

    Sano, Naoki; Yamamoto, Masayoshi; Nagai, Kentaro; Yamada, Keiichi; Ohkohchi, Nobuhiro

    2016-01-01

    The nasogastric tube (NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome (NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube. PMID:27099450

  14. Nasogastric tube syndrome induced by an indwelling long intestinal tube.

    PubMed

    Sano, Naoki; Yamamoto, Masayoshi; Nagai, Kentaro; Yamada, Keiichi; Ohkohchi, Nobuhiro

    2016-04-21

    The nasogastric tube (NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome (NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube.

  15. The pathophysiology of hypertensive acute heart failure.

    PubMed

    Viau, David M; Sala-Mercado, Javier A; Spranger, Marty D; O'Leary, Donal S; Levy, Phillip D

    2015-12-01

    While acute heart failure (AHF) is often regarded as a single disorder, an evolving understanding recognises the existence of multiple phenotypes with varied pathophysiological alterations. Herein we discuss hypertensive AHF and provide insight into a mechanism where acute fluid redistribution is caused by a disturbance in the ventricular-vascular coupling relationship. In this relationship, acute alterations in vascular elasticity, vasoconstriction and reflected pulse waves lead to increases in cardiac work and contribute to decompensated LV function with associated subendocardial ischaemia and end-organ damage. Chronic predisposing factors (neurohormonal activity, nitric oxide insensitivity, arterial stiffening) and physiological stressors (sympathetic surge, volume overload, physical exertion) that are causally linked to acute symptom onset are discussed. Lastly, we review treatment options including both nitrovasodilators and promising novel therapeutics, and discuss future directions in the management of this phenotypic variant.

  16. [Food contamination by pathogens of acute intestinal infections and survival of microorganisms in them under some variants of thermal processing and storage].

    PubMed

    Sergevnin, V I

    2013-01-01

    The contamination of the surface of vegetables and fruits with conditionally pathogenic enterobacteria, intestinal protozoa and enteric viruses has been revealed. The experiment showed an opportunity of penetration of enteric viruses inside of vegetables and fruits with intact (without visible damages) surface. S. enteritidis survive on the shells of the eggs 4 months in the refrigerator, in the albumen and yolk--more than 5 months and in the long storage (more than one month) of chicken eggs in the refrigerator S. enteritidis could penetrate into the egg through the intact shell and multiply in the yolk. It was shown in the experiment on the condition laying of chicken eggs of room temperature in cold water and their subsequent cooking S. enteritidis full destruction of pathogens comes on the 5 minute of heat processing, when the temperature inside the eggs reaches more than 80 degrees C. In mayonnaise at the temperature of the refrigerator S. enteritidis reproduce, but remain viable for 13 days. In the egg powder at the room temperature noted smooth death of S. enteritidis, term viability of microorganisms is 5 months. Addition 10% acetic acid to egg powder in the ratio 1:2 provides for the death of S. enteritidis for a minute. In experimental conditions was established that the processing of chicken on the grill in the process of cooking "Shaverma" provides exemption meat from Salmonella only in the thickness of a piece of up to 2 centimeters. The deeper layers of meat and meat juice which accumulates on the pallet grill, throughout the duration of thermal processing may remain contaminated Salmonella. PMID:24340937

  17. [Food contamination by pathogens of acute intestinal infections and survival of microorganisms in them under some variants of thermal processing and storage].

    PubMed

    Sergevnin, V I

    2013-01-01

    The contamination of the surface of vegetables and fruits with conditionally pathogenic enterobacteria, intestinal protozoa and enteric viruses has been revealed. The experiment showed an opportunity of penetration of enteric viruses inside of vegetables and fruits with intact (without visible damages) surface. S. enteritidis survive on the shells of the eggs 4 months in the refrigerator, in the albumen and yolk--more than 5 months and in the long storage (more than one month) of chicken eggs in the refrigerator S. enteritidis could penetrate into the egg through the intact shell and multiply in the yolk. It was shown in the experiment on the condition laying of chicken eggs of room temperature in cold water and their subsequent cooking S. enteritidis full destruction of pathogens comes on the 5 minute of heat processing, when the temperature inside the eggs reaches more than 80 degrees C. In mayonnaise at the temperature of the refrigerator S. enteritidis reproduce, but remain viable for 13 days. In the egg powder at the room temperature noted smooth death of S. enteritidis, term viability of microorganisms is 5 months. Addition 10% acetic acid to egg powder in the ratio 1:2 provides for the death of S. enteritidis for a minute. In experimental conditions was established that the processing of chicken on the grill in the process of cooking "Shaverma" provides exemption meat from Salmonella only in the thickness of a piece of up to 2 centimeters. The deeper layers of meat and meat juice which accumulates on the pallet grill, throughout the duration of thermal processing may remain contaminated Salmonella.

  18. Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model.

    PubMed

    Heijnen, B H M; Straatsburg, I H; Padilla, N D; Van Mierlo, G J; Hack, C E; Van Gulik, T M

    2006-01-01

    Activation of the complement system contributes to the pathogenesis of ischaemia/reperfusion (I/R) injury. We evaluated inhibition of the classical pathway of complement using C1-inhibitor (C1-inh) in a model of 70% partial liver I/R injury in male Wistar rats (n = 35). C1-inh was administered at 100, 200 or 400 IU/kg bodyweight, 5 min before 60 min ischaemia (pre-I) or 5 min before 24 h reperfusion (end-I). One hundred IU/kg bodyweight significantly reduced the increase of plasma levels of activated C4 as compared to albumin-treated control rats and attenuated the increase of alanine aminotransferase (ALT). These effects were not better with higher doses of C1-inh. Administration of C1-inh pre-I resulted in lower ALT levels and higher bile secretion after 24 h of reperfusion than administration at end-I. Immunohistochemical assessment indicated that activated C3, the membrane attack complex C5b9 and C-reactive protein (CRP) colocalized in hepatocytes within midzonal areas, suggesting CRP is a mediator of I/R-induced, classical complement activation in rats. Pre-ischaemic administration of C1-inh is an effective pharmacological intervention to protect against liver I/R injury.

  19. A systematic review of intermittent pneumatic compression for critical limb ischaemia.

    PubMed

    Moran, Patrick S; Teljeur, Conor; Harrington, Patricia; Ryan, Mairin

    2015-02-01

    Intermittent pneumatic compression (IPC) is designed to aid wound healing and limb salvage for patients with critical limb ischaemia who are not candidates for revascularisation. We conducted a systematic review of the literature to identify and critically appraise the evidence supporting its use in this population. A search was conducted in Embase, MEDLINE and clinical trial registries up to the end of March 2013. No date or language restrictions were applied. Quality assessment was performed by two people independently. Quality was assessed using the Cochrane risk of bias tool and the NICE case-series assessment tool. Two controlled before-and-after (CBA) studies and six case series were identified. One retrospective CBA study involving compression of the calf reported improved limb salvage and wound healing (OR 7.00, 95% CI 1.82 to 26.89, p<0.01). One prospective CBA study involving sequential compression of the foot and calf reported statistically significant improvements in claudication distances and SF-36 quality of life scores. No difference in all-cause mortality was found. Complications included pain associated with compression, as well as skin abrasion and contact rash as a result of the cuff rubbing against the skin. All studies had a high risk of bias. In conclusion, the limited available results suggest that IPC may be associated with improved limb salvage, wound healing and pain management. However, in the absence of additional well-designed analytical studies examining the effect of IPC in critical limb ischaemia, this treatment remains unproven.

  20. Effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice.

    PubMed

    Grewal, Amarjot Kaur; Jaggi, Amteshwar Singh; Rana, Avtar Chand; Singh, Nirmal

    2013-12-01

    The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3α HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect. PMID:24381496

  1. Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model

    PubMed Central

    Liman, Suryamin; Cheung, Chi Wai; Wong, Kar Lok; Tai, Wai; Qiu, Qiu; Ng, Kwok Fu; Choi, Siu Wai; Irwin, Michael

    2015-01-01

    Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS). Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP) model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia) in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56%) rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant). Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P < 0.01) and methylprednisolone (P < 0.05) groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P < 0.05). Proinflammatory cytokines TNF-α and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all P < 0.05). In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain. PMID:26161236

  2. [Physical training as an effective way to protect the heart against ischaemia].

    PubMed

    Korzeniowska Kubacka, Iwona

    2011-01-01

    The findings from experimental animal studies show that regular physical trainings can protect via preconditioning the heart against the ischaemia-reperfusion (IR) injury. It is not clear if the cellular mechanism is the same as in the case of ischaemic preconditioning, but the final effect is the same, i.e. a stress stimulus, in this case a repeated effort leaves the heart with the 'memory', which translates into an increased resistance to ischaemia. At present, the precise mechanism responsible for training-induced cardioprotection is not clear. Candidate factors responsible for this cardioprotection are numerous and include collateral circulation development, enhanced ER stress proteins, increased COX-2 activity, increased heat shock protein (HSP-72) levels, increased activity of mitoK-ATP and sarcoK-ATP channels, and increased myocardial antioxidative capacity. The studies performed so far have suggested that MnSOD activity and increased sarcoK-ATP expression did play a role in exercise-induced cardioprotection. There may exist some other mechanisms responsible for this type of cardioprotection, but finding them will be possible only through further relevant studies. The paper presents the up-to-date knowledge in this field.

  3. 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.

  4. 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.

  5. 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. PMID:26436960

  6. Intestinal protozoa.

    PubMed

    Juckett, G

    1996-06-01

    Giardia is the best known cause of protozoal gastrointestinal disease in North America, producing significant but not life-threatening gastrointestinal distress and diarrhea. Although diagnosis of giardiasis may be challenging, treatment is usually successful. Entamoeba histolytica poses a rarer but far more difficult clinical challenge. Dysentery caused by E. histolytica may be the most feared intestinal protozoal infection, although Cryptosporidium parvum, Balantidium coli, Isospora belli, Sarcocystis species and other newly described protozoa also may cause diarrhea in healthy individuals and may result in intractable, life-threatening illness in patients with acquired immunodeficiency syndrome or other immunosuppressive diseases. Certain protozoa once considered relatively unimportant, such as Cryptosporidium, are now recognized as significant causes of morbidity even in the United States, since transmission readily occurs through contaminated water. PMID:8644565

  7. Xanthine oxidase, but not neutrophils, contributes to activation of cardiac sympathetic afferents during myocardial ischaemia in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Longhurst, John C

    2002-01-01

    Activation of cardiac sympathetic afferents during myocardial ischaemia causes angina and induces important cardiovascular reflex responses. Reactive oxygen species (ROS) are important chemical stimuli of cardiac afferents during and after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of production of hydroxyl radicals. Another potential source of these species is xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes (PMNs) also contribute to the production of ROS in some conditions. The present study tested the hypothesis that both xanthine oxidase-catalysed oxidation of purines and neutrophils provide a source of ROS sufficient to activate cardiac afferents during ischaemia. We recorded single-unit activity of cardiac afferents innervating the ventricles recorded from the left thoracic sympathetic chain (T1-5) of anaesthetized cats to identify the afferents' responses to ischaemia. The role of xanthine oxidase in activation of these afferents was determined by infusion of oxypurinol (10 mg kg−1, i.v.), an inhibitor of xanthine oxidase. The importance of neutrophils as a potential source of ROS in the activation of cardiac afferents during ischaemia was assessed by the infusion of a polyclonal antibody (3 mg ml−1 kg−1, i.v.) raised in rabbits immunized with cat PMNs. This antibody decreased the number of circulating PMNs and, to a smaller extent, platelets. Since previous data suggest that platelets release serotonin (5-HT), which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3 receptor) mechanism, before treatment with the antibody in another group, we blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 μg kg−1, i.v.). We observed that oxypurinol significantly decreased the activity of cardiac afferents during myocardial ischaemia from 1.5 ± 0.4 to 0.8 ± 0.4 impulses s−1. Similarly, the polyclonal antibody significantly reduced the discharge frequency of

  8. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde

    PubMed Central

    Ma, Heng; Guo, Rui; Yu, Lu; Zhang, Yingmei; Ren, Jun

    2011-01-01

    Aims The present study was designed to examine the mechanism involved in mitochondrial aldehyde dehydrogenase (ALDH2)-induced cardioprotection against ischaemia/reperfusion (I/R) injury with a focus on autophagy. Methods Wild-type (WT), ALDH2 overexpression, and knockout (KO) mice (n = 4–6 for each index measured) were subjected to I/R, and myocardial function was assessed using echocardiographic, Langendroff, and edge-detection systems. Western blotting was used to evaluate AMP-dependent protein kinase (AMPK), Akt, autophagy, and the AMPK/Akt upstream signalling LKB1 and PTEN. Results ALDH2 overexpression and KO significantly attenuated and accentuated, respectively, infarct size, factional shortening, and recovery of post-ischaemic left ventricular function following I/R as well as hypoxia/reoxygenation-induced cardiomyocyte contractile dysfunction. Autophagy was induced during ischaemia and remained elevated during reperfusion. ALDH2 significantly promoted autophagy during ischaemia, which was accompanied by AMPK activation and mammalian target of rapamycin (mTOR) inhibition. On the contrary, ALDH2 overtly inhibited autophagy during reperfusion accompanied by the activation of Akt and mTOR. Inhibition and induction of autophagy mitigated ALDH2-induced protection against cell death in hypoxia and reoxygenation, respectively. In addition, levels of the endogenous toxic aldehyde 4-hydroxy-2-nonenal (4-HNE) were elevated by ischaemia and reperfusion, which was abrogated by ALDH2. Furthermore, ALDH2 ablated 4-HNE-induced cardiomyocyte dysfunction and protein damage, whereas 4-HNE directly decreased pan and phosphorylated LKB1 and PTEN expression. Conclusion Our data suggest a myocardial protective effect of ALDH2 against I/R injury possibly through detoxification of toxic aldehyde and a differential regulation of autophagy through AMPK- and Akt-mTOR signalling during ischaemia and reperfusion, respectively. PMID:20705694

  9. Modelling ischaemia in vitro: effects of temperature and glucose concentration on dopamine release evoked by oxygen and glucose depletion in a mouse brain slice.

    PubMed

    Davidson, C; Chauhan, N K; Knight, S; Gibson, C L; Young, A M J

    2011-11-15

    Current pharmacological interventions for acute stroke are largely ineffective or confounded by adverse effects, emphasising the need to develop new pharmacological treatments for neuroprotection. We have developed a robust in vitro model previously used in rats to assess dopamine release in mouse caudate nucleus brain slices, measured by fast cyclic voltammetry, during oxygen and glucose deprivation (OGD) as a model for cerebral ischaemia: this model will allow the study of transgenic mouse strains. During the pre-OGD equilibration period we found that a temperature of 33°C, with solution containing 10 mM glucose provided the optimum baseline conditions from which reliable OGD-induced changes in dopamine efflux could be measured, without being susceptible to spontaneous release events. During OGD we found no significant difference in any of the parameters measured between perfusion with glucose-free solution, and perfusion with solution containing 2 mM glucose. We therefore suggest, in agreement with previous work, that using 2 mM glucose during OGD is appropriate, and using these conditions we were able to reliably produce OGD-evoked dopamine release. PMID:21669225

  10. Modelling ischaemia in vitro: effects of temperature and glucose concentration on dopamine release evoked by oxygen and glucose depletion in a mouse brain slice.

    PubMed

    Davidson, C; Chauhan, N K; Knight, S; Gibson, C L; Young, A M J

    2011-11-15

    Current pharmacological interventions for acute stroke are largely ineffective or confounded by adverse effects, emphasising the need to develop new pharmacological treatments for neuroprotection. We have developed a robust in vitro model previously used in rats to assess dopamine release in mouse caudate nucleus brain slices, measured by fast cyclic voltammetry, during oxygen and glucose deprivation (OGD) as a model for cerebral ischaemia: this model will allow the study of transgenic mouse strains. During the pre-OGD equilibration period we found that a temperature of 33°C, with solution containing 10 mM glucose provided the optimum baseline conditions from which reliable OGD-induced changes in dopamine efflux could be measured, without being susceptible to spontaneous release events. During OGD we found no significant difference in any of the parameters measured between perfusion with glucose-free solution, and perfusion with solution containing 2 mM glucose. We therefore suggest, in agreement with previous work, that using 2 mM glucose during OGD is appropriate, and using these conditions we were able to reliably produce OGD-evoked dopamine release.

  11. 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

  12. 3′,4′-Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep

    PubMed Central

    Wang, Sheng; Dusting, Gregory J; May, Clive N; Woodman, Owen L

    2004-01-01

    The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′-dihydroxyflavonol (DiOHF) to scavenge superoxide in post-I/R myocardium and to prevent myocardial I/R injury. Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH-activated superoxide generation and biochemical markers of injury were measured. DiOHF (10−8–10−4 M) incubated in vitro with post-I/R myocardium from the vehicle group suppressed superoxide production dose-dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro. DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post-I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P<0.01) and IPC (1.7±0.5%; P<0.01) than those in corresponding controls (−1.7±0.4; −2.1±0.4%). DiOHF and IPC improved coronary blood flow to the ischaemic area and preserved higher levels of nitric oxide metabolites in the venous outflow from the ischaemic zone. DiOHF attenuated superoxide production in post-I/R myocardium, and significantly reduced infarct size and injury following I/R in anaesthetized sheep. The extent of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has clinical potential for improving recovery from acute myocardial infarction and other ischaemic syndromes. PMID:15148246

  13. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  14. Increase in skin perfusion pressure after maggot debridement therapy for critical limb ischaemia.

    PubMed

    Maeda, T M; Kimura, C K; Takahashi, K T; Ichimura, K I

    2014-12-01

    Skin perfusion pressure (SPP) is the perfusion pressure at the skin level, and it can serve as an index of peripheral circulation in the skin and subcutaneous tissue. We report a 78-year-old man with critical limb ischaemia who, despite having undergone several catheter interventions, still had severe ulcers with exposed bone on his right foot. We performed transmetatarsal amputation. The tissue around the surgical site became necrotic several days later, and did not respond to conservative therapy. Therefore, we opted for maggot debridement therapy (MDT), given that maggots favour necrotic tissue. After the therapy, SPP around the ulcer increased from 12 to 54 mmHg on the dorsal aspect, and from 17 to 44 mmHg on the plantar aspect. Wound healing was successfully activated by MDT, leading to complete healing within 2.5 months after MDT. We believe that MDT probably contributed to increase the blood supply to the ischaemic wound.

  15. Assessment of chemical lumbar sympathectomy in critical limb ischaemia using thermal imaging.

    PubMed

    Greenstein, D; Brown, T F; Kester, R C

    1994-02-01

    Objective assessment of chemical lumbar sympathectomy (CLS) is lacking. Its success is usually judged in terms of the patient's clinical improvement. We have thermographically measured the immediate temperature changes of the lower limb following CLS using a thermal imager (SAN-EI Thermotracer 6T61). Seven patients with critical limb ischaemia and one patient with Raynaud's phenomenon underwent unilateral ablation of the lumbar sympathetic chain using 5% phenol. Four patients were diabetic, two of whom had undergone previous sympathectomy on the same side. Within fifteen minutes of injection, all patients showed a rise in skin temperature in parts of the sock distribution of between 0.8 degrees C and 8.5 degrees C. We conclude that the haemodynamic effects of CLS are immediate and can be objectively measured with thermal imaging. PMID:8195656

  16. Modelling blood flow and metabolism in the piglet brain during hypoxia-ischaemia: simulating brain energetics.

    PubMed

    Moroz, Tracy; Hapuarachchi, Tharindi; Bainbridge, Alan; Price, David; Cady, Ernest; Baer, Ether; Tachtsidis, Ilias; Broad, Kevin; Ezzati, Mojgan; Robertson, Nicola J; Thomas, David; Golay, Xavier; Cooper, Chris E

    2013-01-01

    We have developed a computational model to simulate hypoxia-ischaemia (HI) in the neonatal piglet brain. It has been extended from a previous model by adding the simulation of carotid artery occlusion and including pH changes in the cytoplasm. Here, simulations from the model are compared with near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (MRS) measurements from two piglets during HI and short-term recovery. One of these piglets showed incomplete recovery after HI, and this is modelled by considering some of the cells to be dead. This is consistent with the results from MRS and the redox state of cytochrome-c-oxidase as measured by NIRS. However, the simulations do not match the NIRS haemoglobin measurements. The model therefore predicts that further physiological changes must also be taking place if the hypothesis of dead cells is correct.

  17. 3-Aminopropanal, formed during cerebral ischaemia, is a potent lysosomotropic neurotoxin.

    PubMed Central

    Li, Wei; Yuan, Xi-Ming; Ivanova, Svetlana; Tracey, Kevin J; Eaton, John W; Brunk, Ulf T

    2003-01-01

    Cytotoxic polyamine-derived amino aldehydes, formed during cerebral ischaemia, damage adjacent tissue (the so-called 'penumbra') not subject to the initial ischaemic insult. One such product is 3-aminopropanal (3-AP), a potent cytotoxin that accumulates in ischaemic brain, although the precise mechanisms responsible for its formation are still unclear. More relevant to the present investigations, the mechanisms by which such a small aldehydic compound might be cytotoxic are also not known, but we hypothesized that 3-AP, having the structure of a weak lysosomotropic base, might concentrate within lysosomes, making these organelles a probable focus of initial toxicity. Indeed, 3-AP leads to lysosomal rupture of D384 glioma cells, a process which clearly precedes caspase activation and apoptotic cell death. Immunohistochemistry reveals that 3-AP concentrates in the lysosomal compartment and prevention of this accumulation by the lysosomotropic base ammonia, NH(3), protects against 3-AP cytotoxicity by increasing lysosomal pH. A thiol compound, N-(2-mercaptopropionyl)glycine, reacts with and neutralizes 3-AP and significantly inhibits cytoxocity. Both amino and aldehyde functions of 3-AP are necessary for toxicity: the amino group confers lysosomotropism and the aldehyde is important for additional, presently unknown, reactions. We conclude that 3-AP exerts its toxic effects by accumulating intralysosomally, causing rupture of these organelles and releasing lysosomal enzymes which initiate caspase activation and apoptosis (or necrosis if the lysosomal rupture is extensive). These results may have implications for the development of new therapeutics designed to lessen secondary damage arising from focal cerebral ischaemia. PMID:12513695

  18. [Assessment of surgical risk in patients with lower limb chronic critical ischaemia].

    PubMed

    Kazakov, Iu I; Lukin, I B; Sokolova, N Iu; Strakhov, M A

    2016-01-01

    Analysed herein are both immediate and remote results of surgical treatment of 93 patients presenting with chronic atherosclerotic occlusion of the femoral-popliteal-tibial segment in the stage of critical ischaemia. The patients were subjected to autovenous femoropopliteal bypass grafting to the isolated arterial segment or balloon angioplasty with stenting of the superficial femoral artery. While choosing the method of arterial reconstruction we assessed concomitant diseases, primarily lesions of the coronary and cerebral circulation. In order to objectively evaluate the patient state, we worked out a scale for assessing surgical risk. Survival rate without amputation after three years in patients with low risk amounted to 71.4%, in those with moderate risk to 60.0%, and in high-risk patients to 43.3%. Patients with initially high risk were found to have a high incidence rate of cardiac and cerebrovascular complications, exceeding 40%. It was shown that the worked out system of assessing the level of surgical risk objectively reflects the prognosis of patient survival following a reconstructive operation. This system of assessment may be appropriate while choosing an optimal method of arterial reconstruction (bypassing operation or endovascular intervention) in patients with atherosclerotic lesions of arteries of the femoropopliteal-tibial segment and critical ischaemia accompanied by severe concomitant pathology. Patients with high surgical risk should preferably be subjected to endovascular reconstruction, while those with low surgical risk should better undergo open shunting bypassing operation, and for those with moderate risk it is acceptable to perform both methods of arterial reconstruction. PMID:27626262

  19. Complications of cerebral angiography for patients with mild carotid territory ischaemia being considered for carotid endarterectomy.

    PubMed Central

    Hankey, G J; Warlow, C P; Molyneux, A J

    1990-01-01

    It is essential to image the carotid bifurcation adequately in patients with symptomatic carotid territory ischaemia if they are being considered for carotid endarterectomy. Optimal resolution is achieved by selective intraarterial contrast angiography which is an invasive procedure carrying some risk. The overall risk-benefit of carotid endarterectomy is currently being investigated in several large randomised trials in Europe and North America. Because cerebral angiography is a prerequisite for carotid endarterectomy, the risks of cerebral angiography will need to be added to those of surgery when considering whether carotid endarterectomy is effective in the management of these patients. This study evaluated prospectively 382 patients with symptomatically mild carotid ischaemia who had cerebral angiography to visualise a potentially resectable lesion at the carotid bifurcation. Complications followed 14 cerebral angiograms in 13 patients (3.4%); two complications were local (0.5%), two systemic (0.5%) and 10 were neurological (2.6%). The neurological complications were transient (TIA 1, generalised seizure 1) in two patients (0.5%), reversible (stroke) in three (0.8%) and permanent (stroke) in five patients (1.3%). There were no deaths. The significant risk factors for post angiographic stroke were (1) stroke before angiography compared with transient ischaemic attacks of the eye or brain and (2) the presence of greater than or equal to 50% diameter stenosis of the symptomatic internal carotid artery; unfortunately it may be the latter patients who are most at risk of stroke as part of the natural history of their disease and therefore most in need of prophylactic carotid endarterectomy (which requires cerebral angiography). The absolute risk of post-angiographic stroke of patients for cerebral angiography using clinical evaluation and Duplex carotid ultrasound screening. PMID:2118171

  20. Complications of cerebral angiography in patients with symptomatic carotid territory ischaemia screened by carotid ultrasound.

    PubMed Central

    Davies, K N; Humphrey, P R

    1993-01-01

    After nearly 40 years, carotid endarterectomy has been shown to be of benefit to patients with symptomatic carotid territory ischaemia and greater than 70% stenosis of the relevant internal carotid artery. Cerebral angiography is performed before surgery and is not without risk. These risks must be added to those of surgery before recommending the procedure to patients. The study evaluated the local, systemic and neurological complications following digital subtraction angiography with selective catheterisation of the carotid arteries in 200 patients presenting to a cerebrovascular clinic for assessment of cerebral ischaemia. All patients had carotid ultrasound screening before angiography to screen out those with normal arteries or mild disease (less than 30% stenosis of symptomatic internal carotid artery). Complications occurred in 28 patients. There were six (3%) local, two (1%) systemic and 20 (10%) neurological complications. Seventeen neurological complications occurred within 24 hours and there were three late complications (24-72 hours). Neurological complications occurred more frequently when angiography was performed by a trainee rather than a consultant neuroradiologist (p < 0.01). The neurological complications were transient (resolved within 24 hours) in 10/200 (5%), reversible (resolved within seven days) in two (1%) and permanent in 8/200 (4%). Two patients died after a stroke and two other patients suffered a disabling stroke. At 24 hours post angiography the permanent (persisting beyond seven days) neurological complication rate was 2.5%. The incidence of total neurological complications and post angiographic strokes was higher in patients with greater than 90% stenosis of the symptomatic internal carotid artery (p < 0.001). The increased use of non-invasive Doppler duplex screening will reduced the absolute number of patients put at risk of angiography, yet the rate of post angiographic complications is likely to increase as patients with severe

  1. Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo

    PubMed Central

    Masini, Emanuela; Cuzzocrea, Salvatore; Mazzon, Emanuela; Marzocca, Cosimo; Mannaioni, Pier Francesco; Salvemini, Daniela

    2002-01-01

    Myocardial injury caused by ischaemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, mast cell activation, and peroxidation of cell membrane lipids. These events are followed by myocardial cell alterations resulting eventually in cell necrosis. An enhanced formation of reactive oxygen species is widely accepted as a stimulus for tissue destruction and cardiac failure. In this study, we have investigated the cardioprotective effects of M40403 in myocardial ischaemia-reperfusion injury. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Ischaemia was induced in rat hearts in vivo by ligating the left anterior descending coronary artery. Thirty minutes after the induction of ischaemia, the ligature was removed and reperfusion allowed to occur for at least 60 min. M40403 (0.1–1 mg kg−1) was given intravenously 15 min before ischaemia. The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose-dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post-reperfusion of the ischaemic myocardium was also reduced by M40403. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P-selectin and for anti-intercellular adhesion molecule (ICAM-1) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in these tissues. No staining for nitrotyrosine, P-selectin or ICAM-1 was found in cardiac tissue taken at the end of the

  2. Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo.

    PubMed

    Masini, Emanuela; Cuzzocrea, Salvatore; Mazzon, Emanuela; Marzocca, Cosimo; Mannaioni, Pier Francesco; Salvemini, Daniela

    2002-07-01

    1. Myocardial injury caused by ischaemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, mast cell activation, and peroxidation of cell membrane lipids. These events are followed by myocardial cell alterations resulting eventually in cell necrosis. An enhanced formation of reactive oxygen species is widely accepted as a stimulus for tissue destruction and cardiac failure. 2. In this study, we have investigated the cardioprotective effects of M40403 in myocardial ischaemia-reperfusion injury. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Ischaemia was induced in rat hearts in vivo by ligating the left anterior descending coronary artery. Thirty minutes after the induction of ischaemia, the ligature was removed and reperfusion allowed to occur for at least 60 min. M40403 (0.1-1 mg kg(-1)) was given intravenously 15 min before ischaemia. 3. The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose-dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post-reperfusion of the ischaemic myocardium was also reduced by M40403. 4. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P-selectin and for anti-intercellular adhesion molecule (ICAM-1) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in these tissues. No staining for nitrotyrosine, P-selectin or ICAM-1 was found in cardiac tissue taken at the end of

  3. Cardiac BMIPP imaging in acute myocardial infarction.

    PubMed

    Nakata, T; Hashimoto, A; Eguchi, M

    1999-02-01

    Fatty acid metabolism functions as a major energy-producing system under aerobic conditions, but it is impaired immediately after myocardial ischaemia. This imaging can provide intracellular information which cannot be obtained by angiographical, perfusional or functional analysis. 123I-BMIPP and perfusion imagings in patients with acute myocardial infarction have demonstrated three different correlations between myocardial perfusion and fatty acid metabolism: concordant defects of perfusion and BMIPP which represent scar or non-viable tissue; lower BMIPP uptake relative to perfusion (perfusion-BMIPP mismatch) which implicates metabolically damaged, often dysynergic, but viable myocardium; and equivalently normal uptakes of perfusion and BMIPP in completely salvaged myocardium. Identification of these perfusion-metabolism correlations contributes to the detection of ischaemia-related myocardial injury in viable and non-viable myocardium, to the prediction of post-ischaemic or post-interventional functional recovery and to the identification of patients who have myocardium at ischaemic risk. Further clinical investigations might reveal more clearly the pathophysiological and prognostic implications of cardiac BMIPP imaging in patients with acute myocardial infarction.

  4. Intestinal Infarction Through Arterial Vascular Obstruction - Case Series from 1st and 3rd Surgery Clinics Cluj-Napoca.

    PubMed

    Jeican, Ionuţ Isaia; Mocan, Mihaela; Gheban, Dan

    2016-01-01

    This article presents a case series of intestinal infarction through obstruction of superior mesenteric artery - two cases of acute mesenteric artery embolism, two cases of acute mesenteric artery thrombosis and a case of volvulus.

  5. Small Intestine Disorders

    MedlinePlus

    Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods ...

  6. Intestinal obstruction repair

    MedlinePlus

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  7. Large intestine (colon) (image)

    MedlinePlus

    ... portion of the digestive system most responsible for absorption of water from the indigestible residue of food. The ileocecal valve of the ileum (small intestine) passes material into the large intestine at the ...

  8. Vasoactive intestinal peptide test

    MedlinePlus

    ... medlineplus.gov/ency/article/003508.htm Vasoactive intestinal peptide test To use the sharing features on this page, please enable JavaScript. Vasoactive intestinal peptide (VIP) is a test that measures the amount ...

  9. Endothelial RAGE exacerbates acute postischaemic cardiac inflammation.

    PubMed

    Ziegler, Tilman; Horstkotte, Melanie; Lange, Philipp; Ng, Judy; Bongiovanni, Dario; Hinkel, Rabea; Laugwitz, Karl-Ludwig; Sperandio, Markus; Horstkotte, Jan; Kupatt, Christian

    2016-08-01

    Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion

  10. The effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease

    PubMed Central

    Patterson, Dean; Kloner, Robert; Effron, Mark; Emmick, Jeffrey; Bedding, Alun; Warner, Margaret; Mitchell, Malcolm; Braat, Simon; MacDonald, Thomas

    2005-01-01

    Objective To investigate the effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease (CAD). Background CAD and erectile dysfunction (ED) share similar risk factors. It is important to know the cardiovascular effects of tadalafil in patients with CAD during physical exertion that is comparable with sexual activity. Methods A randomized, placebo-controlled, double-blind, two-period, crossover study comparing the effects of tadalafil 10 mg and placebo on the time to exercise treadmill test (ETT)-induced myocardial ischaemia in subjects with stable CAD (n = 23; age range: 53–75 years, all exhibited ST-segment depression >1.5 mm at screening ETT at >5METS). Haemodynamic responses to sublingual nitroglycerin (NTG) were assessed before and after ETT. Results Compared with placebo, tadalafil did not significantly affect the time to ETT-induced ischaemia (13 min/31 s vs. 13 min/36 s, respectively). Before exercise, NTG evoked decreases in sitting systolic blood pressure (SBP) that were significantly greater when subjects received tadalafil compared with placebo, and after exercise, more subjects experienced a decrease in SBP <85 mmHg in response to NTG after taking tadalafil vs. placebo. When subjects received tadalafil compared with placebo, SBP was lower at rest (−7 mmHg; −12,-2), during ETT (−10 mmHg; −16, −3), and after ETT (−13 mmHg; −19, −7). Conclusion Tadalafil did not significantly alter the time to ETT-induced ischaemia compared with placebo in subjects with CAD. Tadalafil reduced resting and exercise SBP. Due to the potential for hypotension, the concomitant use of nitrates and tadalafil is contraindicated. PMID:16236035

  11. Effects of ischaemic post-conditioning on the early and late testicular damage after experimental testis ischaemia-reperfusion.

    PubMed

    Minutoli, L; Irrera, N; Squadrito, F; Marini, H; Nicotina, P A; Arena, S; Romeo, C; Antonuccio, P; Altavilla, D

    2014-01-01

    Ischaemic post-conditioning (IPostC) might represent an innovative surgical approach to protect organs from ischaemia and reperfusion (I/R) injury. We investigated the molecular mechanisms underlying the contrasting effects of IPostC on the early and late damage induced by testicular I/R injury. Testis I/R was induced by occluding the right testicular vessels using a clip. Male rats were divided into the following groups: sham, I/R and I/R + IPostC. In the I/R group, the clip was removed after 60 min of ischaemia, and reperfusion was allowed for 30 min, 1 and 30 days. In the I/R + IPostC group, three cycles of 30-sec reperfusion and 30-sec ischaemia were performed after 60 min of ischaemia and then reperfusion followed up for 30 min, 1 and 30 days. Following 30-min reperfusion, there was an increase in mitogen-activated protein kinases (MAPKs) in I/R rats; after 1 day of reperfusion, interleukin-6, tumour necrosis factor-α and nuclear factor-κB (NF-κB) expression were significantly increased; IκB-α expression reduced; and a marked damage in both testes was observed. IPostC inhibited MAPKs, cytokines and NF-κB expression, augmented IκB-α expression and decreased histological damage in testes subjected to I/R. After 30 days of reperfusion, I/R injury activated the apoptosis machinery, caused severe histological damage and reduced spermatogenic activity. By contrast, IPostC did not modify the apoptotic markers, the histological alterations as well as spermatogenic activity following 30 days of reperfusion. Our data demonstrate that IPostC protects the testis from the early damage induced by I/R injury, but it does not protect against the late damage.

  12. Spontaneous pre-existing hypoxia does not affect brain damage after global cerebral ischaemia in late-gestation fetal sheep.

    PubMed

    Davidson, Joanne O; Yuill, Caroline A; Wassink, Guido; Bennet, Laura; Gunn, Alistair J

    2015-01-01

    There is considerable evidence that a mild, non-injurious insult can protect (precondition) against a subsequent injurious insult. Typically, protection is seen when the gap between insults is several days to a week. However, the effect of mild but persistent hypoxia is unknown. In this study we examined the hypothesis that mild pre-existing hypoxia (PaO2<17 mm Hg) would reduce neural injury in chronically instrumented late-gestation (0.85 gestation) fetal sheep exposed to 30 min of global cerebral ischaemia induced by bilateral carotid artery occlusion (normoxia: n=9 vs. pre-existing hypoxia: n=9) or normoxia plus sham ischaemia (sham controls: n=9). Histopathology was assessed after 7 days of recovery. Fetuses with pre-existing hypoxia had lower PaO2 values (16.1±0.6 vs. 26.0±1.1 mm Hg) and were lighter at post-mortem (4,033±412 vs. 5,261±238 g) compared to normoxic fetuses. Cerebral ischaemia was associated with secondary cortical oedema and seizures, reduced final EEG power, loss of sleep state cycling, and significant loss of neurons and oligodendrocytes, with no significant effect of pre-existing hypoxia. Pre-existing hypoxia was associated with a significantly attenuated rise in mean arterial pressure between 18 and 36 h and slower resolution of cortical oedema between 96 and 150 h after ischaemia. These data suggest that chronic hypoxia is not associated with a significant preconditioning effect.

  13. 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. PMID:27292534

  14. KATP channel blocker does not abolish the protective effect of NHE1 inhibition against ischaemia/reperfusion in aged myocardium

    PubMed Central

    Liu, Hong; Moore, Peter G

    2010-01-01

    Background and objective Aging is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na+/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate if NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium. Methods Hearts from 24-month old rats were assigned to 4 groups: (1) Control group; (2) APC group perfused with 2.5% sevoflurane before ischemia; (3) HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; (4) HOE+5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury. Results Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEq/kg/dry weight in control group and 55±7 in HOE group (p<0.05). Intracellular Ca++ was 1764±142 nM in control group and 694±213 in HOE group (p<0.05). Infarct size was measured at 28±4% in control group vs. 17±2% in HOE group (p<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared to control (p<0.05). The beneficial effects of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups. Conclusions NHE inhibition was effective in protecting myocardium from I/R injury in aged rats whereas APC was not. 5HD failed to block the protective effect of NHE inhibition. PMID:20216068

  15. Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation.

    PubMed

    Cheon, So Yeong; Cho, Kyoung Joo; Song, Juhyun; Kim, Gyung Whan

    2016-04-01

    Reactive astrocytes play an essential role in determining the tissue response to ischaemia. Formation of a glial scar can block the neuronal outgrowth that is required for restoration of damaged tissue. Therefore, regulation of astrocyte activation is important; however, the mediator of this process has not been fully elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is an early responder to oxidative stress, and plays a pivotal role in the intracellular signalling pathway of apoptosis, inflammation, and differentiation. To confirm whether ASK1 mediates astrocyte activation and leads to glial scar formation after cerebral ischaemia, we conducted in vivo and in vitro experiments. C57BL/6 mice were subjected to occlusion of the middle cerebral artery, and astrocyte cultures were exposed to oxygen-glucose deprivation. After silencing of ASK1 , astrocyte-associated genes were downregulated, as seen with the use of microarrays. The glial fibrillary acidic protein (GFAP) level was decreased, and correlated with the reduction in the ASK1 level. In astrocytes, reduction in the ASK1 level decreased the activity of the p38 pathway, and the levels of transcription factors for GFAP and GFAP transcripts after hypoxia. In the chronic phase, ASK1 depletion reduced glial scar formation and conserved neuronal structure, which may lead to better functional recovery. These data suggest that ASK1 may be an important mediator of ischaemia-induced astrocyte activation and scar formation, and could provide a potential therapeutic target for treatment after ischaemic stroke. PMID:26797817

  16. Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling.

    PubMed

    Fan, Guanwei; Yu, Jiahui; Asare, Patrick Fordjour; Wang, Lingyan; Zhang, Han; Zhang, Boli; Zhu, Yan; Gao, Xiumei

    2016-10-01

    The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre-treatment of DSS significantly improved cell survival and protected against I/R-induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy- and apoptosis-related proteins (including p62, LC3-II, Beclin-1, Bax, and Caspase-3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre-treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation. PMID:27385290

  17. Healing of intestinal inflammation by IL-22

    PubMed Central

    Mizoguchi, Atsushi

    2012-01-01

    An IL-10 family cytokine IL-22 is characterized by several unique biological properties, including 1) the target restricted to innate cells, 2) the distinct expression pattern between large and small intestines, 3) alteration of the cellular source depending on several factors, 4) the dual abilities to serve as protective versus proinflammatory mediators in inflammatory responses, and 5) the close association with some major IBD susceptibility genes. The major functions of IL-22 in the intestine are the stimulation of epithelial cells to produce a wide variety of antibacterial proteins, the reinforcement of mucus barrier through stimulation of mucin 1 production under intestinal inflammatory conditions, and the enhancement of epithelial regeneration with goblet cell restitution. Through these beneficial functions, IL-22 contributes to the improvement of some types of experimental chronic colitis, which are mediated by Th1 or Th2 responses. Most importantly, studies using both loss-of-function and gain-of-function approaches have clearly demonstrated the ability of IL-22 to promote intestinal wound healing from acute intestinal injury. These findings highlight IL-22 as an attractive and promising target for future IBD therapy. Alternatively, the enormous progress in the field of IL-22 biology has also suggested more complicated mechanism with IL-22 pathway than previously predicted. This review article briefly summarizes previous and current knowledge on IL-22 particularly associated with intestinal inflammation. PMID:22359410

  18. Exercise, intestinal barrier dysfunction and probiotic supplementation.

    PubMed

    Lamprecht, Manfred; Frauwallner, Anita

    2012-01-01

    Athletes exposed to high-intensity exercise show an increased occurrence of gastrointestinal (GI) symptoms like cramps, diarrhea, bloating, nausea, and bleeding. These problems have been associated with alterations in intestinal permeability and decreased gut barrier function. The increased GI permeability, a so-called 'leaky gut', also leads to endotoxemia, and results in increased susceptibility to infectious and autoimmune diseases, due to absorption of pathogens/toxins into tissue and the bloodstream. Key components that determine intestinal barrier function and GI permeability are tight junctions, protein structures located in the paracellular channels between epithelial cells of the intestinal wall. The integrity of tight junctions depends on sophisticated interactions between the gut residents and their expressed substances, the intestinal epithelial cell metabolism and the activities of the gut-associated lymphoid tissue. Probiotic supplements are an upcoming group of nutraceuticals that could offer positive effects on athlete's gut and entire health. Some results demonstrate promising benefits for probiotic use on the athlete's immune system. There is also evidence that probiotic supplementation can beneficially influence intestinal barrier integrity in acute diseases. With regard to exercise-induced GI permeability problems, there is still a lack of studies with appropriate data and a gap to understand the underlying mechanisms to support such health beneficial statements implicitly. This article refers (i) to exercise-induced intestinal barrier dysfunction, (ii) provides suggestions to estimate increased gut barrier permeability in athletes, and (iii) discusses the potential of probiotic supplementation to counteract an exercise-induced leaky gut. PMID:23075554

  19. Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy.

    PubMed

    Hodges, H; Nelson, A; Virley, D; Kershaw, T R; Sinden, J D

    1997-04-01

    Global ischaemia induced by interruption of cerebral blood flow results in damage to vulnerable cells, notably in the CA1 and hilar hippocampal fields, and is frequently associated with memory deficits. This review examines cognitive deficits that occur in animal models of global ischaemia in rats and monkeys, the extent to which these deficits are associated with CA1 cell loss, and the evidence for functional recovery following transplants of foetal CA1 cells and grafts of conditionally immortalised precursor cells. In rats, impairments are seen most consistently in tasks of spatial learning and spatial working memory dependent on use of allocentric environmental cues. In monkeys, ischaemic deficits have been shown to a moderate extent in delayed object recognition tasks, but animals with a selective excitotoxic CA1 lesion show a profound impairment in conditional discrimination tasks, suggesting that these may be a more sensitive measure of ischaemic impairments. Several studies have reported correlational links between the extent of CA1 cell loss following two or four vessel occlusion (2 VO, 4 VO) in rats and behavioural impairments, but recent findings indicate that at intermediate levels of damage these relationships are weak and variable, and emerge clearly only when animals with maximal CA1 cell loss are included, suggesting that the deficits involve more than damage to the CA1 field. Nevertheless, ischaemic rats and CA1-lesioned marmosets with grafts of foetal CA1 cells show substantial improvements; in rats these are not found with grafts from other hippocampal fields. Conditionally immortalised cell lines and trophic grafts are currently being assessed for their functional potential in animal models, because clinical use of foetal cells will not be practicable. Recent findings suggest that an expanded population of neuroepithelial cells derived from the conditionally immortalised H-2Kb-tsA58 transgenic mouse improve spatial learning as effectively as CA1

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

    PubMed Central

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

    2016-01-01

    Background/Aims 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. Methods 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. Results 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. Conclusions DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway. PMID:27114435

  1. Vertebrate Intestinal Endoderm Development

    PubMed Central

    Spence, Jason R.; Lauf, Ryan; Shroyer, Noah F.

    2010-01-01

    The endoderm gives rise to the lining of the esophagus, stomach and intestines, as well as associated organs. To generate a functional intestine, a series of highly orchestrated developmental processes must occur. In this review, we attempt to cover major events during intestinal development from gastrulation to birth, including endoderm formation, gut tube growth and patterning, intestinal morphogenesis, epithelial reorganization, villus emergence as well as proliferation and cytodifferentiation. Our discussion includes morphological and anatomical changes during intestinal development as well as molecular mechanisms regulating these processes. PMID:21246663

  2. Pre-Analytical Determination of the Effect of Extended Warm or Cold Ischaemia on RNA Stability in the Human Ileum Mucosa.

    PubMed

    Lee, Serene M L; Schelcher, Celine; Thasler, Reinhard; Schiergens, Tobias S; Thasler, Wolfgang E

    2015-01-01

    The use of banked human tissue, obtained with informed consent after elective surgical procedures, represents a powerful model for understanding underlying mechanisms of diseases or therapeutic interventions and for establishing prognostic markers. However, donated tissues typically have varying times of warm ischaemia in situ due to blood arrest or cold ischaemia due to procurement and transportation. Hence, before using these tissues, it is important to carry out pre-analytical studies to ensure that they are representative of the in vivo state. In particular, tissues of the gastrointestinal tract have been thought to have low RNA stability. Therefore, this study aimed to determine if extended warm or cold ischaemia times and snap-freezing or banking in RNA stabilization solution affects RNA integrity or gene expression in human ileum mucosa. In short, ileum mucosa was collected for up to 1.5 h and 6 h of simulated warm or cold ischaemia respectively. Subsequently, RNA integrity and gene expressions were determined. It was found that RNA integrity remained high over the course of warm and cold ischaemia examined and there were in general no significant differences between snap-freezing and banking in RNA stabilization solution. Following the same trend, there were in general no significant changes in gene expressions measured (MYC, HIF1α, CDX, HMOX1 and IL1β). In conclusion, RNA in the ileum mucosa is maintained at a high integrity and has stable gene expression over the examined time course of warm or cold ischaemia when banked in RNA stabilization solution or snap-frozen in liquid nitrogen. As the average warm and cold ischaemia times imposed by surgery and the process of tissue banking are shorter than the time period examined in this study, human ileum mucosa samples collected after surgeries could be used for gene expression studies. PMID:26371767

  3. Nicotinamide-rich diet protects the heart against ischaemia-reperfusion in mice: a crucial role for cardiac SUR2A.

    PubMed

    Sukhodub, Andriy; Du, Qingyou; Jovanović, Sofija; Jovanović, Aleksandar

    2010-06-01

    It is a consensus view that a strategy to increase heart resistance to ischaemia-reperfusion is a warranted. Here, based on our previous study, we have hypothesized that a nicotinamide-rich diet could increase myocardial resistance to ischaemia-reperfusion. Therefore, the purpose of this study was to determine whether nicotinamide-rich diet would increase heart resistance to ischaemia-reperfusion and what is the underlying mechanism. Experiments have been done on mice on control and nicotinamide-rich diet (mice were a week on nicotinamide-rich diet) as well as on transgenic mice overexpressing SUR2A (SUR2A mice), a regulatory subunit of cardioprotective ATP-sensitive K(+) (K(ATP)) channels and their littermate controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR, whole heart and single cell resistance to ischaemia-reperfusion and severe hypoxia was measured by TTC staining and laser confocal microscopy, respectively. Nicotinamide-rich diet significantly decreased the size of myocardial infarction induced by ischaemia-reperfusion (from 42.5+/-4.6% of the area at risk zone in mice on control diet to 26.8+/-1.8% in mice on nicotinamide-rich diet, n=6-12, P=0.031). The cardioprotective effect of nicotinamide-rich diet was associated with 11.46+/-1.22 times (n=6) increased mRNA levels of SUR2A in the heart. HMR1098, a selective inhibitor of the sarcolemmal K(ATP) channels opening, abolished cardioprotection afforded by nicotinamide-rich diet. Transgenic mice with a sole increase in SUR2A expression had also increased cardiac resistance to ischaemia-reperfusion. We conclude that nicotinamide-rich diet up-regulate SUR2A and increases heart resistance to ischaemia-reperfusion.

  4. Pre-Analytical Determination of the Effect of Extended Warm or Cold Ischaemia on RNA Stability in the Human Ileum Mucosa

    PubMed Central

    Thasler, Reinhard; Schiergens, Tobias S.; Thasler, Wolfgang E.

    2015-01-01

    The use of banked human tissue, obtained with informed consent after elective surgical procedures, represents a powerful model for understanding underlying mechanisms of diseases or therapeutic interventions and for establishing prognostic markers. However, donated tissues typically have varying times of warm ischaemia in situ due to blood arrest or cold ischaemia due to procurement and transportation. Hence, before using these tissues, it is important to carry out pre-analytical studies to ensure that they are representative of the in vivo state. In particular, tissues of the gastrointestinal tract have been thought to have low RNA stability. Therefore, this study aimed to determine if extended warm or cold ischaemia times and snap-freezing or banking in RNA stabilization solution affects RNA integrity or gene expression in human ileum mucosa. In short, ileum mucosa was collected for up to 1.5 h and 6 h of simulated warm or cold ischaemia respectively. Subsequently, RNA integrity and gene expressions were determined. It was found that RNA integrity remained high over the course of warm and cold ischaemia examined and there were in general no significant differences between snap-freezing and banking in RNA stabilization solution. Following the same trend, there were in general no significant changes in gene expressions measured (MYC, HIF1α, CDX, HMOX1 and IL1β). In conclusion, RNA in the ileum mucosa is maintained at a high integrity and has stable gene expression over the examined time course of warm or cold ischaemia when banked in RNA stabilization solution or snap-frozen in liquid nitrogen. As the average warm and cold ischaemia times imposed by surgery and the process of tissue banking are shorter than the time period examined in this study, human ileum mucosa samples collected after surgeries could be used for gene expression studies. PMID:26371767

  5. Establishment of Intestinal Bacteriology

    PubMed Central

    MITSUOKA, Tomotari

    2014-01-01

    Research on intestinal bacteria began around the end of the 19th century. During the last 5 decades of the 20th century, research on the intestinal microbiota made rapid progress. At first, in my work, I first developed a method of comprehensive analysis of the intestinal microbiota, and then I established classification and identification methods for intestinal anaerobes. Using these methods I discovered a number of ecological rules governing the intestinal microbiota and the role of the intestinl microbiota in health and disease. Moreover, using germfree animals, it was proven that the intestinal microbiota has a role in carcinogenesis and aging in the host. Thus, a new interdisciplinary field, “intestinal bacteriology” was established. PMID:25032084

  6. Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism.

    PubMed

    van den Brom, Charissa E; Bulte, Carolien Se; Loer, Stephan A; Bouwman, R Arthur; Boer, Christa

    2013-01-01

    Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury. However, there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus. A strong predictor of postoperative cardiac function is myocardial substrate metabolism. In the type 2 diabetic heart, substrate metabolism is shifted from glucose utilisation to fatty acid oxidation, resulting in metabolic inflexibility and cardiac dysfunction. The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state, which may deteriorate cardiac function even further in case of type 2 diabetes mellitus.Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism. Interventions that target at restoration of metabolic derangements, like lifestyle and pharmacological interventions, may therefore be an interesting candidate to reduce perioperative complications. This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia. PMID:23452502

  7. Subintimal angioplasty for superficial femoral artery occlusion: poor patency in critical ischaemia.

    PubMed Central

    Smith, B. M.; Stechman, M.; Gibson, M.; Torrie, E. P. H.; Magee, T. R.; Galland, R. B.

    2005-01-01

    INTRODUCTION: Subintimal angioplasty has been proposed for the treatment of long segment occlusive disease and for patients with critical limb ischaemia (CLI) with significant co-morbidity. There is no consensus as to short- and long-term patency. We present our experience with this technique. METHODS: Between 1995 and 2000, 43 consecutive patients (48 limbs) underwent subintimal angioplasty for superficial femoral artery occlusions. Outcome measures were haemodynamic and/or symptomatic patency. RESULTS: Technical success was achieved in 14/17 limbs with CLI (82%) and 30/31 (97%) with intermittent claudication (IC). There were 7 complications (15%), 6 occurring in the claudicant group. The median occlusion length was 10 cm for CLI and 6 cm for IC. Patency at 12 and 36 months, on an intention-to-treat basis, was 69% and 58% for claudicants and 25% and 25% for patients with CLI (P = 0.0005 and P = 0.0044, respectively). Following only technically successful procedures, 12-month patency was 72% (IC) and 31% (CLI) (P = 0.009). Patients with occlusions > or = 10 cm were more likely to re-occlude than those < 10 cm (12-month patency 60% versus 25%;P = 0.037). CONCLUSIONS: In this series, short- and long-term patency in patients with CLI is poor. Subintimal angioplasty in the treatment of CLI should be reserved for those patients not fit for surgical bypass. PMID:16176697

  8. Outcomes of kidney paired donation transplants in relation to shipping and cold ischaemia time.

    PubMed

    Allen, Richard; Pleass, Henry; Clayton, Phil A; Woodroffe, Claudia; Ferrari, Paolo

    2016-04-01

    To assess the impact of shipping distance and cold ischaemia time (CIT) of shipped organs in a kidney paired donation (KPD) programme, we evaluated the outcomes of the initial 100 kidney transplants performed in the Australian KPD programme. In a 44-month period, 12 centres were involved in fifteen 2-way, twenty 3-way, one 4-way and one 6-way exchanges. Sixteen kidneys were transplanted at the same hospital (CIT 2.6 ± 0.6 h) and 84 required transport to the recipient hospital (CIT 6.8 ± 2.8 h). A spontaneous fall in serum creatinine by at least 10% within 24 h was observed in 85% of recipients, with no difference between nonshipped and shipped kidneys. There were two cases of transient delayed graft function requiring dialysis and patient and graft survival at 1 year were 99% and 97%, respectively. There was no difference in recipients of nonshipped compared with shipped kidneys with regard to serum creatinine at 1 month (mean difference (MD) 7.3 μmol/l, 95% CI -20.2 to 34.8, P = 0.59), 1-year graft survival (MD 3.9%, 95% CI -5.4 to 13.2, P = 0.41) or patient survival (MD -2.4%, 95% CI -10.0 to 5.2, P = 0.54). Despite prolonged CIT for interstate exchanges, the programme's decision to ship donor kidneys rather than the donor appears to be safe.

  9. Cardiac CT for myocardial ischaemia detection and characterization—comparative analysis

    PubMed Central

    Bucher, A M; De Cecco, C N; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

    2014-01-01

    The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials. PMID:25135617

  10. Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36

    PubMed Central

    Li, Shiguo; Liu, Chao; Gu, Lei; Wang, Lina; Shang, Yongliang; Liu, Qiong; Wan, Junyi; Shi, Jian; Wang, Fang; Xu, Zhiliang; Ji, Guangju

    2016-01-01

    Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart. PMID:27512143

  11. Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia

    PubMed Central

    Bainbridge, Alan; Robertson, Nicola J.; Cooper, Chris E.

    2015-01-01

    Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. PMID:26445281

  12. Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state.

    PubMed

    Collins, P; Ford, I; Greaves, M; Macaulay, E; Brittenden, J

    2006-08-01

    Platelet and coagulation activation are implicated in the increased incidence of ischaemic events seen in patients with peripheral arterial disease. This study aimed to assess the effect of surgical revascularisation on platelet aggregation and coagulation in patients with severe limb ischaemia (SLI). Twenty-two patients had blood samples taken: prior to surgery, on reperfusion, 2, 24 and 48 h post-surgery. Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system. Thrombin-antithrombin III Complex (TAT) and D-dimer were measured by ELISA. COX-mediated aggregation increased significantly at reperfusion and remained elevated at 24 h [median increase from baseline of 9% (range -16 to 33%) P = 0.011]. TRAP-stimulated aggregation increased significantly at reperfusion and remained elevated at 2 h post-surgery [median increase 18% (range -71 to 45%); P = 0.007]. TAT levels were significantly elevated from reperfusion and remained so at 48 h (P < 0.003), whereas D-dimer only increased at 24 h (P = 0.014). For the first time, we have demonstrated that in patients with SLI, platelet aggregation is increased following surgery and there is a mismatch in the balance between the coagulation and fibrinolytic pathways despite the use of aspirin and heparin. Thus in the early post-operative these patients exhibit a pro-thrombotic state. PMID:16928603

  13. Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia

    PubMed Central

    Carlucci, Annalisa; Adornetto, Annagrazia; Scorziello, Antonella; Viggiano, Davide; Foca, Mariapaola; Cuomo, Ornella; Annunziato, Lucio; Gottesman, Max; Feliciello, Antonio

    2008-01-01

    A-kinase anchor protein 121 (AKAP121) assembles a multivalent signalling complex on the outer mitochondrial membrane that controls persistence and amplitude of cAMP and src signalling to mitochondria, and plays an essential role in oxidative metabolism and cell survival. Here, we show that AKAP121 levels are regulated post-translationally by the ubiquitin/proteasome pathway. Seven In-Absentia Homolog 2 (Siah2), an E3–ubiquitin ligase whose expression is induced in hypoxic conditions, formed a complex and degraded AKAP121. In addition, we show that overexpression of Siah2 or oxygen and glucose deprivation (OGD) promotes Siah2-mediated ubiquitination and proteolysis of AKAP121. Upregulation of Siah2, by modulation of the cellular levels of AKAP121, significantly affects mitochondrial activity assessed as mitochondrial membrane potential and oxidative capacity. Also during cerebral ischaemia, AKAP121 is degraded in a Siah2-dependent manner. These findings reveal a novel mechanism of attenuation of cAMP/PKA signaling, which occurs at the distal sites of signal generation mediated by proteolysis of an AKAP scaffold protein. By regulating the stability of AKAP121-signalling complex at mitochondria, cells efficiently and rapidly adapt oxidative metabolism to fluctuations in oxygen availability. PMID:18323779

  14. The effect of concentration and duration of normobaric oxygen in reducing caspase-3 and -9 expression in a rat-model of focal cerebral ischaemia.

    PubMed

    Chen, Suyan; Peng, Huizhen; Rowat, Anne; Gao, Feng; Zhang, Zhenxiang; Wang, Peng; Zhang, Weihong; Wang, Xianyuan; Qu, Lixia

    2015-08-27

    The aim of this study was to determine the effect of different concentrations of normobaric oxygen (NBO) on neurological function and the expression of caspase-3 and -9 in a rat model of acute cerebral ischaemia. Sprague-Dawley rats (n=120) were randomly divided into four groups (n=30 per group), including 3 groups given NBO at concentrations of 33%, 45% or 61% and one control group given air (21% oxygen). After 2h of ischaemic occlusion, each group was further subdivided into six subgroups (n=5) during reperfusion according to the duration (3, 6, 12, 24, 48 or 72h) and concentration of NBO (33%, 45% or 61%) or air treatment. The Fluorescence Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to detect caspase-3 and -9 mRNA and protein relative expression respectively. The Neurologic Impairment Score (NIS) was significantly lower in rats given 61% NBO ≥3h after reperfusion when compared to the control group (P<0.05, Mann-Whitney U). NBO significantly reduced caspase-3 and -9 mRNA and protein expression when compared to the control group at all NBO concentrations and time points (P<0.05, ANOVA). The expression of caspase-3 and -9 was lower in the group given 61% NBO compared any other group, and this difference was statistically significant when compared to the group given 33% NBO for ≥48h and the control group (both P<0.05, ANOVA). These findings indicate that NBO may inhibit the apoptotic pathway by reducing caspase-3 and -9 expression, thereby promoting neurological functional recovery after stroke.

  15. Intestinal aGVHD and infection after hematopoietic stem cell transplantation

    PubMed Central

    Hou, Cai-yan; Xu, Li-li; Chen, Hu; Liu, Na; Jiang, Ming; Wang, Guo-quan; Zhang, Linlin; Wang, Xiao-hong; Zeng, Yan-jun

    2013-01-01

    Background We aimed to guide clinical nursing by studying the relationship between intestinal acute graft-versus-host disease and intestinal infection after hematopoietic stem cell transplantation. Material/Methods We present an effective nursing method by comparing and analyzing the degree, duration time, and volume of diarrhea, and the distribution of pathogens in 44 patients who developed intestinal aGVHD after hematopoietic stem cell transplantation (24 patients with no intestinal infection). Results 21.4% of patients with grade I–II intestinal aGVHD developed into intestinal infection and 87.5% of patients with grade III–IV intestinal aGVHD developed into intestinal infection (P<0.05). Higher mortality was found in the grade III–IV intestinal aGVHD patients with intestinal infection. Patient age had no effect on the incidence of GVHD according to our data (P<0.05). We found remarkable differences in the amount and duration of diarrhea between patients with and without intestinal infection (P<0.05). The most common pathogens cultivated were Candida glabrata (24%) and Candida albicans (22.67%). Conclusions The incidence of intestinal infection increased remarkably after intestinal aGVHD occurred. Severe aGVHD can easily lead to fungus infection. Nursing care can decrease the incidence of intestinal infection in aGVHD. PMID:24077343

  16. Malathion-induced sublethal toxicity on the intestine of cricket frog (Fejervarya limnocharis).

    PubMed

    Kundu, Chayya Roy; Roychoudhury, Shubhadeep; Capcarova, Marcela

    2011-01-01

    The effect of malathion [diethyl(dimethoxythiophosphorylthio)succinate] at sublethal concentration (0.006 ppm) on intestinal parameters of cricket frog (Fejervarya limnocharis) was studied for 24 hrs to 240 hrs of exposure and remarkable histopathological alterations were observed. The study on intestinal parameters revealed acute pathological conditions in the intestinal wall. The toxic effect became evident as the cytoplasm of the cells disintegrated and the cells became empty and vacuolated. The cell membranes were also ruptured. Degenerative changes of the absorptive surface (villi) of the intestine in the different periods of exposure were pronounced. Severe atrophic nature (necrotic mucosa) of the intestine began from 48 hrs onwards to 96 hrs of exposure.

  17. Effects of systemic non-steroidal anti-inflammatory drugs on nociception during tail ischaemia and on reperfusion hyperalgesia in rats.

    PubMed Central

    Gelgor, L.; Butkow, N.; Mitchell, D.

    1992-01-01

    1. We have investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) on nociception during ischaemia and on reperfusion hyperalgesia in rats. 2. We induced tail ischaemia in conscious rats by applying a tourniquet at the base of the tail until the rats exhibited co-ordinated escape behaviour when we released the tourniquet. 3. We assessed hyperalgesia by measuring the tail flick latency following tail immersion in water at 49 degrees C, before applying and immediately after releasing the tourniquet, and then at 30 min intervals for 2 h. 4. Intraperitoneal injection of NSAIDs prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia, nor on tail flick latency in the absence of prior ischaemia. However all the drugs attenuated reperfusion hyperalgesia in a log dose-dependent manner. Doses required to abolish hyperalgesia, were indomethacin 5 mg kg-1, diclofenac sodium 42 mg kg-1, ibuprofen 54 mg kg-1, dipyrone 168 mg kg-1 and paracetamol 170 mg kg-1. 5. We conclude that the mechanisms underlying nociception during ischaemia are not the same as those underlying reperfusion hyperalgesia. Moreover our procedure provides a rapid and more humane method for measuring the antinociceptive potency of NSAIDs. PMID:1559131

  18. Small intestinal obstruction caused by anisakiasis.

    PubMed

    Takano, Yuichi; Gomi, Kuniyo; Endo, Toshiyuki; Suzuki, Reika; Hayashi, Masashi; Nakanishi, Toru; Tateno, Ayumi; Yamamura, Eiichi; Asonuma, Kunio; Ino, Satoshi; Kuroki, Yuichiro; Nagahama, Masatsugu; Inoue, Kazuaki; Takahashi, Hiroshi

    2013-01-01

    Small intestinal anisakiasis is a rare disease that is very difficult to diagnose, and its initial diagnosis is often surgical. However, it is typically a benign disease that resolves with conservative treatment, and unnecessary surgery can be avoided if it is appropriately diagnosed. This case report is an example of small intestinal obstruction caused by anisakiasis that resolved with conservative treatment. A 63-year-old man admitted to our department with acute abdominal pain. A history of raw fish (sushi) ingestion was recorded. Abdominal CT demonstrated small intestinal dilatation with wall thickening and contrast enhancement. Ascitic fluid was found on the liver surface and in the Douglas pouch. His IgE (RIST) was elevated, and he tested positive for the anti-Anisakis antibodies IgG and IgA. Small intestinal obstruction by anisakiasis was highly suspected and conservative treatment was performed, ileus tube, fasting, and fluid replacement. Symptoms quickly resolved, and he was discharged on the seventh day of admission. Small intestinal anisakiasis is a relatively uncommon disease, the diagnosis of which may be difficult. Because it is a self-limiting disease that usually resolves in 1-2 weeks, a conservative approach is advisable to avoid unnecessary surgery. PMID:24455340

  19. Reduced antioxidant level and increased oxidative damage in intact liver lobes during ischaemia-reperfusion

    PubMed Central

    Váli, László; Taba, Gabriella; Szentmihályi, Klára; Fébel, Hedvig; Kurucz, Tímea; Pallai, Zsolt; Kupcsulik, Péter; Blázovics, Anna

    2006-01-01

    AIM: To determine whether increased blood flow of the liver can cause oxidative stress and hepatocyte damage, and to elaborate methods suitable for measuring the antioxidant defence during hepatic surgery on rat model. METHODS: In nembutal narcosis, the left lateral and the medial lobes of the liver were clipped for 45 min to make the total blood supply flow through the other lobes. Total antioxidant status, glutathione peroxidase and superoxide dysmutase activity, as well as the concentrations of diene conjugates and free sulphydril groups, H-donating ability and reducing power of the liver samples were determined. Chemiluminescent intensity of the liver was also measured. Metal ions (Al, Ca, Cu, Fe, Mg, Mn, Zn) and P and S concentrations of the liver were determined with an inductively coupled plasma optical emission spectrometer and Se content was measured by cathodic stripping voltammetry. RESULTS: Glutathione peroxidase and superoxide dysmutase activities of the liver decreased significantly in the hyperemia group compared to those observed in the sham operated group. The level of total antioxidant status was also significantly lower in the hyperemia group. H-donating ability, reducing power and free sulphydril group concentration showed the same tendency. A significant correlation (P<0.05) was found between the changes in non-specific antioxidant activities. This pointed to simultaneous activity of the antioxidant defence system. Al, Cu, Mn, Zn, and S were lower in the hyperemia group than in the sham operated group when the levels of Ca, Fe, Mg, Se and P ions were higher during hyperemia. CONCLUSION: Oxidative stress is one of the main factors for the injury of intact liver lobes during ischaemia-reperfusion. PMID:16534850

  20. Alleviation of myocardial ischaemia after administration of the cardioselective beta adrenoceptor antagonist bevantolol.

    PubMed

    Hartog, J M; Verdouw, P D

    1986-04-01

    A 15 min reduction in blood flow in the left anterior descending coronary artery to 35% of baseline in open chest anaesthetised pigs produced a 25% decrease in cardiac output and a similar fall in maximum left ventricular dP/dt, whereas left ventricular filling pressure increased from 10(1) to 14(1) mmHg. The decrease in perfusion of the myocardial area nourished by the left anterior descending coronary artery was not evenly distributed since the endocardial to epicardial flow ratio decreased from 0.93(0.07) to 0.48(0.06). Regional myocardial wall thickening of the ischaemic segment decreased from 0.36(0.03) to 0.14(0.03), whereas the arterial-coronary venous differences in pH and PCO2 tripled. Subsequently, eight animals received 1.5 mg X kg-1 of the cardioselective beta adrenoceptor antagonist bevantolol, whereas seven other animals were treated with the solvent. In the following 15 min the cardiovascular performance of the solvent treated animals did not change appreciably, although there was a tendency to further deterioration. Bevantolol did not improve transmural myocardial blood flow to the ischaemic zone but caused a redistribution in favour of the endocardial layers since the endocardial to epicardial flow ratio almost returned to baseline. These changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and PCO2, but regional myocardial function did not improve. In another series of experiments, however, bevantolol (1.5 mg X kg-1) decreased the velocity of regional wall thickening of normal myocardium by 22(2)% as a result of its negative inotropic properties. Thus bevantolol appears to alleviate ischaemia, and the increase in diastolic perfusion time (17%) may be one of the major mechanisms.

  1. Correction of biochemical and functional disorders in brain ischaemia with laser therapy

    NASA Astrophysics Data System (ADS)

    Musienko, Julia I.; Nechipurenko, Natalia I.; Vasilevskaya, Ludmila A.

    2005-08-01

    Application of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with red helium-neon laser (HNL) with 630 nm wavelength and different powers on blood oxygen transport (BOT), cerebral and dermal microhaemodynamics (MGD), hydro-ion balance in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of BOT disturbance, ionic disbalance and edema in the ischemic brain region. Microcirculation disturbances with worsening of the cerebral and dermal MHD were revealed. ILIB with HNL radiation of 2.5 and 4.5 mW powers provokes dehydratation of brain structure alone with the K+, Na+ concentration decreasing and hemoglobin-oxygen affinity increasing in intact group of animals. There was not revealed marked changes of cerebral MHD condition here. Using of ILIB in rabbits after LIB contributes for improving function of BOT, normalizing of water content in all cerebral structures compared to operated animals. Preventive ILIB provoked improvement of speckl-optical parameters and marked protective effect on microhaemodynamics processes in superficial brain structures. HNL radiation with 1.0 mW power results in worsening of oxygen transport, cerebral and skin MHD, hydro-ion homeostasis in animals with LIB modeling. Thus, laser haemotherapy contributes for improving of hydro-ion status, blood oxygen transport and cerebral microcirculation in brain ischemia, what allows considering that helium-neon radiation with the pointed regimen is substantiated pathogenetically in brain ischaemia.

  2. Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia

    PubMed Central

    Hadoke, Patrick W. F.; Takov, Kaloyan; Korczak, Agnieszka; Denvir, Martin A.; Smith, Lee B.

    2016-01-01

    Aims Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall. Methods and Results Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10−10–10-7M; 6 days). Conclusion These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis. PMID:27159530

  3. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    PubMed Central

    Yilmaz, Tonguç Utku; Yazihan, Nuray; Dalgic, Aydın; Kaya, Ezgi Ermis; Salman, Bulent; Kocak, Mehtap; Akcil, Ethem

    2015-01-01

    Background & objectives: Erythropoietin (EPO) has cytoprotective and anti-apoptotic effects in pathological conditions, including hypoxia and ischaemia-reperfusion injury. One of the targets to protect against injury is ATP-dependent potassium (KATP) channels. These channels could be involved in EPO induced ischaemic preconditoning like a protective effect. We evaluated the cell cytoprotective effects of EPO in relation to KATP channel activation in the renal tubular cell culture model under hypoxic/normoxic conditions. Methods: Dose and time dependent effects of EPO, KATP channel blocker glibenclamide and KATP channel opener diazoxide on cellular proliferation were evaluated by colorimetric assay MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] under normoxic and hypoxic conditions in human renal proximal tubular cell line (CRL-2830). Evaluation of the dose and time dependent effects of EPO, glibenclamide and diazoxide on apoptosis was done by caspase-3 activity levels. Hypoxia inducible factor-1 alpha (HIF-1 α) mRNA levels were measured by semi-quantative reverse transcription polymerase chain reaction (RT)-PCR. Kir 6.1 protein expresion was evalutaed by Western blot. Results: Glibenclamide treatment decreased the number of living cells in a time and dose dependent manner, whereas EPO and diazoxide treatments increased. Glibenclamide (100 μM) treatment significantly blocked the anti-apoptotic effects of EPO (10 IU/ml) under both normoxic and hypoxic conditions. EPO (10 IU/ml) and diazoxide (100 μM) treatments significantly increased (P<0.01) whereas glibenclamide decreased (P<0.05) HIF-1 α mRNA expression. Glibenclamide significantly (P<0.01) decreased EPO induced HIF-1 α mRNA expression when compared with the EPO alone group. Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic

  4. 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

  5. Opposite roles of bradykinin B1 and B2 receptors during cerebral ischaemia-reperfusion injury in experimental diabetic rats.

    PubMed

    Sang, Hongfei; Liu, Ling; Wang, Liumin; Qiu, Zhongming; Li, Min; Yu, Linjie; Zhang, Hao; Shi, Ruifeng; Yu, Shuhong; Guo, Ruibing; Ye, Ruidong; Liu, Xinfeng; Zhang, Renliang

    2016-01-01

    Bradykinin receptors play important roles in cerebral ischaemia-reperfusion (I/R) injury of non-diabetics. Their functions in diabetics, however, have not been studied. In this study, we hypothesized that bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R) would be upregulated and participate in the regulation of diabetic ischaemic stroke. To investigate this, we first evaluated B1R and B2R expression at different time points after I/R in non-diabetic and diabetic rats (Sprague-Dawley) by using real-time quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. Then, pharmacological inhibitors were separately administered via the tail vein to analyse their effects on cerebral ischaemia in diabetics. Both receptors were significantly upregulated after cerebral I/R in non-diabetic and diabetic rats. B1R expression in diabetic rats increased in a sharper manner than in non-diabetic rats, whereas B2R expression increased to the same level during the early stage of reperfusion but later became lower. Interestingly, the upregulated B1R was expressed in astrocytes, whereas B2R was mainly located in neurons in the ischaemic penumbra. Functional studies showed that inhibition of B1R significantly reduced infarct volume, neurological deficits, cell apoptosis, and neuron degeneration, probably by attenuating blood-brain barrier (BBB) disruption and post-ischaemic inflammation, at 24 h after reperfusion. In contrast, B2R antagonist had opposite effects, and exacerbated BBB penetrability and tissue inflammation. These findings suggest that B1R and B2R have detrimental and beneficial effects, respectively in diabetic cerebral ischaemia, which might open new avenues for the treatment of ischaemic stroke in diabetic patients through selective pharmacological blockade or activation.

  6. Comparison between superficial femoral artery stenting and bypass surgery in severe lower-limb ischaemia: a retrospective study

    PubMed Central

    Islam, J; Robbs, JV

    2015-01-01

    Summary Background Symptomatic femoro-popliteal disease is treated by bypass surgery or angioplasty with or without stenting. The aim of this study was to compare the results of stenting and bypass surgery with regard to limb salvage in patients with severe leg ischaemia. Methods A total of 213 patients with femoro-popliteal disease presenting with severe claudication or critical limb ischaemia between January 2009 and December 2013 were evaluated; 118 patients (139 limbs) had stents placed and 95 patients (104 limbs) had bypass surgery. Most (60%) presented with critical limb ischaemia (rest pain 40%, tissue necrosis 20%), and the remainder with severe claudication. The treatment groups had matching risk factors. Results The average age was 66 years and 73% were male. Tissue necrosis was found in 26% of the stent group and 12% of the bypass group (p = 0.009). In the stent group 26% had adjunctive procedures, compared to 16% in the bypass group (p = 0.138). During the one-year follow up, there were 30 stent occlusions (22%) and 18 graft occlusions (17%) (p = 0.42). There were 14 major amputations (10%) in the stent group, and 13 (13%) in the bypass group (p = 0.68). Limb salvage rate was 90% in the stent group, and 88% in the bypass group (p = 0.68). There were no peri-operative deaths in the stent group, but one in the bypass group (1%). One-year mortality rate was equal (8%) in both groups (p = 1.00). Conclusion One-year outcome was comparable in both groups with regard to mortality, stent or graft patency and limb salvage rates. PMID:25784315

  7. Effects of polydeoxyribonucleotide on the histological damage and the altered spermatogenesis induced by testicular ischaemia and reperfusion in rats.

    PubMed

    Minutoli, L; Antonuccio, P; Squadrito, F; Bitto, A; Nicotina, P A; Fazzari, C; Polito, F; Marini, H; Bonvissuto, G; Arena, S; Morgia, G; Romeo, C; Caputi, A P; Altavilla, D

    2012-04-01

    The effects of polydeoxyribonucleotide (PDRN), an agonist of the A2A adenosine receptors which when activated positively influences sperm activity, were tested in an experimental testicular ischaemia/reperfusion injury model. Anaesthetized male Sprague-Dawley rats were subjected to testicular torsion-induced ischaemia, followed by reperfusion (TI/R). Immediately after detorsion, randomized animals, including SHAM, received intraperitoneal injections of: (i) vehicle (1 mL/kg 0.9% NaCl solution); (ii) PDRN (8 mg/kg); (iii) DMPX (3,7-dimethyl-1-propargilxanthine, 0.1 mg/kg); or (iv) PDRN (8 mg/kg) + DMPX (0.1 mg/kg). Animals were euthanized at 1, 7 and 30 days following reperfusion. Vascular endothelial growth factor (VEGF) expression is normally associated with adenosine A2A receptor stimulation. After treatment, VEGF mRNA/protein expression quantified by qPCR and Western blot, vascular endothelial growth factor receptor-1 (VEGFR1) and endothelial nitric oxide synthase (eNOS) mRNA measured by qPCR, VEGF and VEGFR1 assessed using immunohistochemical methods, histological staining and spermatogenic activity were all analysed. Testis ischaemia-reperfusion (TI/R) injury caused increases in VEGF mRNA and protein, VEGFR1 and eNOS mRNA, histological damage and reduced spermatogenic activity. Immunostaining showed a lower expression of VEGF in germinal epithelial cells and a strong expression of VEGFR1 in Leydig cells after TI/R. PDRN administration increased significantly VEGF message/protein, VEGFR1 and eNOS message, decreased histological damage and ameliorated spermatogenic activity. PDRN might be useful in the management of testicular torsion.

  8. Anti-apoptotic effect of succinyl gelatine in a liver ischaemia-reperfusion injury model (Bcl-2, Bax, Caspase 3)?

    PubMed

    Altunkan, Ali; Aydin, Ozlem; Ozer, Zeliha; Colak, Tahsin; Bilgin, Egemen; Oral, Uğur

    2002-06-01

    Apoptosis of tissues may contribute to ischaemia-reperfusion injury. The aim of the present study was to determine whether administration of a colloid solution would prevent apoptosis after liver ischaemia-reperfusion. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either 4% SG (20 ml kg (-1)h(-1) ) by 30 min of intravenous (i.v.) infusion (Group I, n= 7) or equivalent volumes of 0.9% sodium chloride (Group II, n= 6) i.v. before a 45 min interruption of the portal vein blood flow and then 45 min of reperfusion. The animals were killed following the reperfusion period. Their livers were processed for histopathological examination and paraffin sections of these tissues were examined. The expression of Bcl-2, Bax and caspase 3 were analysed by immunohistochemistry. ANOVA and the Wilcoxon W -test were used for statistical analysis, and mean values were expressed +/-sd. Histologically, the foci of ischaemic necrosis were observed in liver specimens of the periportal area in one of the animals in Group I and in two in Group II. Immunhistochemical analysis demonstrated an increase in Bcl-2 protein levels in Group I compared to Group II ( P< 0.05). Bax expression was lower in Group I than in Group II. Immunoreactivity for caspase 3 did not differ significantly between the two groups (47.0 +/- 35.93 in Group I, 32.83 +/- 23.63 in Group II). Our results indicate that gelofusine did not protect the liver tissue against ischaemia-reperfusion-induced apoptosis.

  9. Acute colonic pseudo-obstruction (Ogilvie's syndrome) with caecal perforation after caesarean section

    PubMed Central

    Khajehnoori, Masoomeh; Nagra, Sonal

    2016-01-01

    Ogilvie syndrome or acute colonic pseudo-obstruction is characterized by acute dilatation of the colon usually involving caecum and right hemi-colon in the absence of any mechanical obstruction. It is usually associated with an underlying severe illness/infection or surgery, mostly caesarean section and rarely occurs spontaneously. Identification of this condition is important due to the increased risk of bowel ischaemia and perforation particularly with caecal diameter >9 cm. This is a case report of bowel perforation following caesarean section leading to urgent laparotomy. PMID:27554827

  10. Acute colonic pseudo-obstruction (Ogilvie's syndrome) with caecal perforation after caesarean section.

    PubMed

    Khajehnoori, Masoomeh; Nagra, Sonal

    2016-01-01

    Ogilvie syndrome or acute colonic pseudo-obstruction is characterized by acute dilatation of the colon usually involving caecum and right hemi-colon in the absence of any mechanical obstruction. It is usually associated with an underlying severe illness/infection or surgery, mostly caesarean section and rarely occurs spontaneously. Identification of this condition is important due to the increased risk of bowel ischaemia and perforation particularly with caecal diameter >9 cm. This is a case report of bowel perforation following caesarean section leading to urgent laparotomy. PMID:27554827

  11. 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

  12. 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.

  13. Effects of hypoxia and ischaemia on coronary vascular resistance, A-V node conduction and S-A node excitation.

    PubMed

    Berne, R M; Belardinelli, L

    1985-01-01

    Hypoxia and ischaemia produce relaxation of the vascular smooth muscle of the resistance vessels in the myocardium. A low pH may contribute to the arteriolar dilatation but cannot account for the major response. In all likelihood the reduced pO2 acts indirectly by release of a vasodilator mediator rather than by a direct effect on the vascular muscle. Potassium release may account for a transient component of the vasodilation, but it appears that a major factor is the release of adenosine from the ischaemic tissue. Adenosine also appears to be responsible for slowing of the sinus rate and impaired A-V conduction in myocardial ischaemia. These observations are of clinical significance because hypoxia-induced A-V block, such as may occur in inferior myocardial infarction, can be abolished by an adenosine antagonist such as aminophylline. In contrast, adenosine is also useful in the treatment of some cardiac arrhythmias. Supraventricular tachycardia, in which the A-V node is involved in the re-entrant pathway, is readily abolished in humans by the intravenous administration of small doses of adenosine.

  14. Impact of caloric restriction on myocardial ischaemia/reperfusion injury and new therapeutic options to mimic its effects

    PubMed Central

    Rohrbach, Susanne; Aslam, Muhammad; Niemann, Bernd; Schulz, Rainer

    2014-01-01

    Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. Short- and long-term CR confers cardio protection against ischaemia/reperfusion injury in young and even in aged rodents. A few human trials suggest that CR has the potential to mediate improvement of cardiac or vascular function and induce retardation of cardiac senescence also in humans. The underlying mechanisms are diverse and have not yet been clearly defined. Among the known mediators for the benefits of CR are NO, the AMP-activated PK, sirtuins and adiponectin. Mitochondria, which play a central role in such complex processes within the cell as apoptosis, ATP-production or oxidative stress, are centrally involved in many aspects of CR-induced protection against ischaemic injury. Here, we discuss the relevant literature regarding the protection against myocardial ischaemia/reperfusion injury conferred by CR. Furthermore, we will discuss drug targets to mimic CR and the possible role of calorie restriction in preserving cardiovascular function in humans. PMID:24611611

  15. Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia

    PubMed Central

    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

    2015-01-01

    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. PMID:26656460

  16. Multidetector CT in emergency radiology: acute and generalized non-traumatic abdominal pain.

    PubMed

    Paolantonio, Pasquale; Rengo, Marco; Ferrari, Riccardo; Laghi, Andrea

    2016-01-01

    Multidetector CT (MDCT) is an imaging technique that provides otherwise unobtainable information in the diagnostic work-up of patients presenting with acute abdominal pain. A correct working diagnosis depends essentially on understanding the individual patient's clinical data and laboratory findings. In haemodynamically stable patients with acute severe and generalized abdominal pain, MDCT is now the preferred imaging test and gives invaluable diagnostic information, also in unstable patients after stabilization. In this descriptive review, we focus our attention on acute, severe and generalized or undifferentiated non-traumatic abdominal pain. The main differential diagnoses are acute pancreatitis, gastrointestinal perforation, ruptured abdominal aneurysm and acute mesenteric ischaemia. We will provide radiologist readers with a technical guide to optimize MDCT imaging protocols and list the major CT signs essential to reach a correct diagnosis and guide the best treatment. PMID:26689097

  17. Intestinal adaptation after massive intestinal resection

    PubMed Central

    Weale, A; Edwards, A; Bailey, M; Lear, P

    2005-01-01

    Patients with short bowel syndrome require long term parenteral nutrition support. However, after massive intestinal resection the intestine undergoes adaptation and nutritional autonomy may be obtained. Given that the complications of parenteral nutrition may be life threatening or result in treatment failure and the need for intestinal transplantation, a more attractive option is to wean patients off nutrition support by optimising the adaptive process. The article examines the evidence that after extensive small bowel resection adaptation occurs in humans and focuses on the factors that influence adaptation and the strategies that have been used to optimise this process. The review is based on an English language Medline search with secondary references obtained from key articles. There is evidence that adaptation occurs in humans. Adaptation is a complex process that results in response to nutrient and non-nutrient stimuli. Successful and reproducible strategies to improve adaptation remain elusive despite an abundance of experimental data. Nevertheless given the low patient survival and quality of life associated with other treatments for irreversible intestinal failure it is imperative that clinical research continues into the optimisation of the adaptation. PMID:15749794

  18. Effects of ischaemia and hypoxia on the development of the nervous system in acardiac foetus.

    PubMed

    Laure-Kamionowska, Milena; Maślińska, Danuta; Deregowski, Krzysztof; Piekarski, Paweł; Raczkowska, Barbara

    2004-01-01

    cerebrovasculosa area. The effect of ischaemia in the presented case is the anomalous formation of the cerebral structures. The morphological features imply that the failure occurred after neurulation and before the prosencephalic began to grow. The failure of neural tube formation occurred on the 22nd-25th day of gestation. The malformed formation of the nervous system might be caused by impaired induction due to altered gene expression or to the interference of exogenous agents that interrupt normal development. The haemodynamic abnormal placental circulation, which induced lack of oxygen supply and nutritional deficiency, implies the morphological pattern of the anomaly.

  19. Intestinal colonization resistance

    PubMed Central

    Lawley, Trevor D; Walker, Alan W

    2013-01-01

    Dense, complex microbial communities, collectively termed the microbiota, occupy a diverse array of niches along the length of the mammalian intestinal tract. During health and in the absence of antibiotic exposure the microbiota can effectively inhibit colonization and overgrowth by invading microbes such as pathogens. This phenomenon is called ‘colonization resistance’ and is associated with a stable and diverse microbiota in tandem with a controlled lack of inflammation, and involves specific interactions between the mucosal immune system and the microbiota. Here we overview the microbial ecology of the healthy mammalian intestinal tract and highlight the microbe–microbe and microbe–host interactions that promote colonization resistance. Emerging themes highlight immunological (T helper type 17/regulatory T-cell balance), microbiota (diverse and abundant) and metabolic (short-chain fatty acid) signatures of intestinal health and colonization resistance. Intestinal pathogens use specific virulence factors or exploit antibiotic use to subvert colonization resistance for their own benefit by triggering inflammation to disrupt the harmony of the intestinal ecosystem. A holistic view that incorporates immunological and microbiological facets of the intestinal ecosystem should facilitate the development of immunomodulatory and microbe-modulatory therapies that promote intestinal homeostasis and colonization resistance. PMID:23240815

  20. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  1. Early management of acute pancreatitis.

    PubMed

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  2. Pediatric intestinal motility disorders

    PubMed Central

    Gfroerer, Stefan; Rolle, Udo

    2015-01-01

    Pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected patient. Furthermore, some of these conditions might also have implications for adulthood. Pediatric intestinal motility disorders frequently present as chronic constipation in toddler age children. Most of these conditions are functional, meaning that constipation does not have an organic etiology, but in 5% of the cases, an underlying, clearly organic disorder can be identified. Patients with organic causes for intestinal motility disorders usually present in early infancy or even right after birth. The most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn period. This sign is highly indicative of the presence of Hirschsprung disease (HD), which is the most frequent congenital disorder of intestinal motility. HD is a rare but important congenital disease and the most significant entity of pediatric intestinal motility disorders. The etiology and pathogenesis of HD have been extensively studied over the last several decades. A defect in neural crest derived cell migration has been proven as an underlying cause of HD, leading to an aganglionic distal end of the gut. Numerous basic science and clinical research related studies have been conducted to better diagnose and treat HD. Resection of the aganglionic bowel remains the gold standard for treatment of HD. Most recent studies show, at least experimentally, the possibility of a stem cell based therapy for HD. This editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis, dysganglionosis, chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine metaplasia. Underlying organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as

  3. In vivo 31P NMR OSIRIS of bioenergetic changes in rabbit kidneys during and after ischaemia: effect of pretreatment with an indeno-indole compound.

    PubMed

    Sørensen, V; Jonsson, O; Pettersson, S; Scherstén, T; Soussi, B

    1998-04-01

    Changes in energy phosphates of rabbit kidneys subjected to ischaemia-reperfusion have been measured in vivo with volume selective 31P NMR spectroscopy. The effects of pretreatment with a new lipid peroxidation inhibitor (indeno-indol derivate--code name H290/51) on the bioenergetic changes were analysed. The left kidney was moved to a subcutaneous pocket to facilitate exact positioning over the surface coil. A 1H NMR image was acquired and a 3.5-mL cube selected for 31P NMR spectra. 31P NMR spectra were recorded before occlusion of the left renal artery, during 1 h of ischaemia and 2 hours of reperfusion. Ischaemia induced drastic changes in the levels of inorganic phosphates and ATP as well as intracellular acidosis. A normalization was observed during reperfusion. Two hours after reperfusion significantly higher values for beta-ATP/Pi and intracellular pH were recorded in the animals pretreated with H290/51. The present technique allows quantitative analyses of changes in kidney bioenergetics in vivo during different experimental conditions. The importance of ischaemia-reperfusion induced lipid peroxidation for mitochondrial function is emphasized.

  4. Identification of regulated genes during permanent focal cerebral ischaemia: characterization of the protein kinase 9b5/MARKL1/MARK4.

    PubMed

    Schneider, Armin; Laage, Rico; von Ahsen, Oliver; Fischer, Achim; Rossner, Moritz; Scheek, Sigrid; Grünewald, Sylvia; Kuner, Rohini; Weber, Daniela; Krüger, Carola; Klaussner, Bettina; Götz, Bernhard; Hiemisch, Holger; Newrzella, Dieter; Martin-Villalba, Ana; Bach, Alfred; Schwaninger, Markus

    2004-03-01

    Cerebral ischaemia induces transcriptional changes in a number of pathophysiologically important genes. Here we have systematically studied gene expression changes after 90 min and 24 h of permanent focal ischaemia in the mouse by an advanced fragment display technique (restriction-mediated differential display). We identified 56 transcriptionally altered genes, many of which provide novel hints to ischaemic pathophysiology. Particularly interesting were two pro-apoptotic genes (Grim19 and Tdag51), whose role in cerebral ischaemia and neuronal cell death has not been recognized so far. Among the unknown sequences, we identified a gene that was rapidly and transiently up-regulated. The encoded protein displayed high homology to the MARK family of serine-threonine protein kinases and has recently been described as MARKL1/MARK4. Here we demonstrate that this protein is a functional protein kinase with the ability to specifically phosphorylate a cognate peptide substrate for the AMP-kinase family. Upon overexpression in heterologous cells, the functional wild-type protein, but not its kinase-dead mutant, led to decreased cell viability. We conclude that the up-regulation of this kinase during focal ischaemia may represent an interesting new target for pharmacological intervention. PMID:15009667

  5. 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…

  6. A fine structural modification of glycosaminoglycans is correlated with the progression of muscle regeneration after ischaemia: towards a matrix-based therapy?

    PubMed

    Chevalier, F; Arnaud, D; Henault, E; Guillevic, O; Siñeriz, F; Ponsen, A C; Papy-Garcia, D; Barritault, D; Letourneur, D; Uzan, G; Meddahi-Pellé, A; Hlawaty, H; Albanese, P

    2015-09-04

    Critical limb ischaemia often leads to amputation of the limb and potential mortality. Moreover, there are still significant problems with current therapeutic treatments, according to poor revascularisation of degenerated tissue probably due to modifications within the microenvironment. This study is focused on the changes of structure and bioactivity of glycosaminoglycans (GAGs), especially heparan sulphate (HS) and chondroitin sulphate (CS) in rat Extensor Digitorum Longus (EDL) muscle after ischaemia. Male Wistar rats were subjected to ischaemic-injury by ligation of the neurovascular trunk accompanying EDL-tendon. After 4, 8, 15, 21, 60 and 90 d, the rats were sacrificed and the muscles were collected and submitted to histological, biochemical and gene expression assays. We demonstrated that ischaemia induced modification of expression of enzymes involved in GAG biosynthesis which correlated with significant changes in HS and CS structural features such as size and sulphation pattern. These major structural changes are associated to modifications of GAG abilities to bind growth factors and to modulate cell activity. Moreover, a CS hallmark of injury is maintained as well after the regeneration process. Finally, we showed the relevance of the role of this glycanic matrix remodelling, since a GAG mimetic treatment accelerated muscle repair after ischaemia.

  7. l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro.

    PubMed

    Banerjee, Aditi; Ghatak, Swagata; Sikdar, Sujit Kumar

    2016-07-01

    Brain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus. We show that 15-30 mmol/L l-lactate increases functional TREK1 protein expression by 1.5-3-fold in hippocampal astrocytes using immunostaining and electrophysiology. Studies with transcription blocker actinomycin-D and quantitative PCR indicate that the increase in TREK1 expression is due to enhanced TREK1 mRNA transcription. We further report that l-lactate-mediated increase in TREK1 expression is via protein kinase A (PKA)-dependent pathway. This is the first report of an ischaemic metabolite affecting functional expression of an ion channel. Our studies in an in vitro model of ischaemia using oxygen glucose deprivation show that 30 mmol/L l-lactate fails to reduce cell death in rat hippocampal slices treated with TREK1 blockers, PKA inhibitors and gliotoxin. The above effects were specific to l-lactate as pyruvate failed to increase TREK1 expression and reduce cell death. l-Lactate-induced TREK1 upregulation is a novel finding of physiological significance as TREK1 channels contribute to neuroprotection by enhancing potassium buffering and glutamate clearance capacity of astrocytes. We propose that l-lactate promotes neuronal survival in hippocampus by increasing TREK1 channel expression via PKA pathway in astrocytes during ischaemia. Insufficient blood supply to the brain leads to cerebral ischaemia and increase in extracellular lactate concentrations. We incubated hippocampal astrocytes in lactate and observed increase in TREK1 channel expression via

  8. l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro.

    PubMed

    Banerjee, Aditi; Ghatak, Swagata; Sikdar, Sujit Kumar

    2016-07-01

    Brain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus. We show that 15-30 mmol/L l-lactate increases functional TREK1 protein expression by 1.5-3-fold in hippocampal astrocytes using immunostaining and electrophysiology. Studies with transcription blocker actinomycin-D and quantitative PCR indicate that the increase in TREK1 expression is due to enhanced TREK1 mRNA transcription. We further report that l-lactate-mediated increase in TREK1 expression is via protein kinase A (PKA)-dependent pathway. This is the first report of an ischaemic metabolite affecting functional expression of an ion channel. Our studies in an in vitro model of ischaemia using oxygen glucose deprivation show that 30 mmol/L l-lactate fails to reduce cell death in rat hippocampal slices treated with TREK1 blockers, PKA inhibitors and gliotoxin. The above effects were specific to l-lactate as pyruvate failed to increase TREK1 expression and reduce cell death. l-Lactate-induced TREK1 upregulation is a novel finding of physiological significance as TREK1 channels contribute to neuroprotection by enhancing potassium buffering and glutamate clearance capacity of astrocytes. We propose that l-lactate promotes neuronal survival in hippocampus by increasing TREK1 channel expression via PKA pathway in astrocytes during ischaemia. Insufficient blood supply to the brain leads to cerebral ischaemia and increase in extracellular lactate concentrations. We incubated hippocampal astrocytes in lactate and observed increase in TREK1 channel expression via

  9. Heat Stress Reduces Intestinal Barrier Integrity and Favors Intestinal Glucose Transport in Growing Pigs

    PubMed Central

    Pearce, Sarah C.; Mani, Venkatesh; Boddicker, Rebecca L.; Johnson, Jay S.; Weber, Thomas E.; Ross, Jason W.; Rhoads, Robert P.; Baumgard, Lance H.; Gabler, Nicholas K.

    2013-01-01

    Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na+/K+ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport. PMID:23936392

  10. Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs.

    PubMed

    Pearce, Sarah C; Mani, Venkatesh; Boddicker, Rebecca L; Johnson, Jay S; Weber, Thomas E; Ross, Jason W; Rhoads, Robert P; Baumgard, Lance H; Gabler, Nicholas K

    2013-01-01

    Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35-50% humidity; n=8) or HS conditions (35°C; 24-43% humidity; n=8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P=0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P=0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na(+)/K(+) ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P=0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.

  11. Regulation of intestinal lipid absorption by clock genes.

    PubMed

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders. PMID:25033063

  12. Regulation of intestinal lipid absorption by clock genes.

    PubMed

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

  13. Intestinal pseudo-obstruction

    MedlinePlus

    ... Taking drugs that slow intestinal movements. These include narcotic (pain) medicines and drugs used when you are ... that may have caused the problem (such as narcotic drugs) may help. In severe cases, surgery may ...

  14. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the bloodstream. The pyloric sphincter governs the passage of partly digested food ...

  15. Selective IK blockade as an antiarrhythmic mechanism: effects of UK66,914 on ischaemia and reperfusion arrhythmias in rat and rabbit hearts.

    PubMed Central

    Rees, S. A.; Curtis, M. J.

    1993-01-01

    1. UK66,914 is a specific and selective blocker of the delayed rectifying potassium current (IK). The effectiveness of IK block as a mechanism for prevention of ischaemia- and reperfusion-induced arrhythmias was tested by use of UK66,914: its actions in rat, a species deficient in cardiac IK were compared with its actions in rabbit, a species possessing functional cardiac IK. Antiarrhythmic actions in rabbit but none in rat is the only outcome possible if selective IK blockade is responsible for the antiarrhythmic actions of the drug during ischaemia and/or reperfusion. 2. During 30 min regional ischaemia, 0.3 and 1 microM UK66,914 had no influence on the incidence of ventricular fibrillation (VF) in rat (n = 9/group), values being 78% in controls, 100% in 0.3 microM-treated hearts and 78% in 1.0 microM-treated hearts (NS). UK66,914 also had no effect on reperfusion-induced VF incidence (100% in each group), nor on the latency to onset of ischaemia- or reperfusion-induced arrhythmias. In contrast, in rabbit (n = 13/group), similar concentrations of drug reduced the incidence of reperfusion-induced VF from 77% in controls, to 38% and 31% (P < 0.05) respectively. The incidence of ischaemia-induced arrhythmias was too low in controls to permit detection of an antiarrhythmic effect in rabbit; however no drug-induced proarrhythmia was seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8428204

  16. Neuroprotective effects of preconditioning ischaemia on ischaemic brain injury through inhibition of mixed-lineage kinase 3 via NMDA receptor-mediated Akt1 activation.

    PubMed

    Yin, Xiao-Hui; Zhang, Quan-Guang; Miao, Bei; Zhang, Guang-Yi

    2005-05-01

    A number of works show that the mitogen-activated protein kinase (MAPK) signalling pathway responds actively in cerebral ischaemia and reperfusion. We undertook our present studies to clarify the role of mixed-lineage kinase 3 (MLK3), a MAPK kinase kinase (MAPKKK) in MAPK cascades, in global ischaemia and ischaemic tolerance. The mechanism concerning NMDA receptor-mediated Akt1 activation underlying ischaemic tolerance, was also investigated. Sprague-Dawley rats were subjected to 6 min of ischaemia and differing times of reperfusion. Our results showed MLK3 was activated in the hippocampal CA1 region with two peaks occurring at 30 min and 6 h, respectively. This activation returned to base level 3 days later. Both preconditioning with 3 min of sublethal ischaemia and NMDA pretreatment inhibited the 6-h peak of activation. However, pretreatment of ketamine before preconditioning reversed the inhibiting effect of preconditioning on MLK3 activation at 6 h of reperfusion. In the case of Akt1, however, preconditioning and NMDA pretreatment enhanced Akt1 activation at 10 min of reperfusion. Furthermore, ketamine pretreatment reversed preconditioning-induced increase of Akt1 activation. We also noted that pretreatment of LY294002 before preconditioning reversed both the inhibition of MLK3 activation at 6 h of reperfusion and the increase in Akt1 activation at 10 min of reperfusion. The above-mentioned results lead us to conclude that, in the hippocampal CA1 region, preconditioning inhibits MLK3 activation after lethal ischaemia and reperfusion and, furthermore, this effect is mediated by Akt1 activation through NMDA receptor stimulation.

  17. Lower limb ischaemia in patients with diabetic foot ulcers and gangrene: recognition, anatomic patterns and revascularization strategies.

    PubMed

    Mills, Joseph L

    2016-01-01

    The confluence of several chronic conditions--in particular ageing, peripheral artery disease, diabetes, and chronic kidney disease--has created a global wave of lower limbs at risk for major amputation. While frequently asymptomatic or not lifestyle limiting, at least 1% of the population has peripheral artery disease of sufficient severity to be limb threatening. To avoid the critical error of failing to diagnose ischaemia, all patients with diabetic foot ulcers and gangrene should routinely undergo physiologic evaluation of foot perfusion. Ankle brachial index is useful when measurable, but may be falsely elevated or not obtainable in as many as 30% of patients with diabetic foot ulcers primarily because of medial calcinosis. Toe pressures and skin perfusion pressures are applicable to such patients.

  18. Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

    PubMed Central

    Watts, Ryan P.; Thom, Ogilvie; Fraser, John F.

    2013-01-01

    Brain death is associated with dramatic and serious pathophysiologic changes that adversely affect both the quantity and quality of organs available for transplant. To fully optimise the donor pool necessitates a more complete understanding of the underlying pathophysiology of organ dysfunction associated with transplantation. These injurious processes are initially triggered by catastrophic brain injury and are further enhanced during both brain death and graft transplantation. The activated inflammatory systems then contribute to graft dysfunction in the recipient. Inflammatory mediators drive this process in concert with the innate and adaptive immune systems. Activation of deleterious immunological pathways in organ grafts occurs, priming them for further inflammation after engraftment. Finally, posttransplantation ischaemia reperfusion injury leads to further generation of inflammatory mediators and consequent activation of the recipient's immune system. Ongoing research has identified key mediators that contribute to the inflammatory milieu inherent in brain dead organ donation. This has seen the development of novel therapies that directly target the inflammatory cascade. PMID:23691272

  19. Early myocardial ischaemia: evaluation of the histochemical haematoxylin-basic fuchsin-picric acid (HBFP) staining technique.

    PubMed

    Van Reempts, J; Borgers, M; Reneman, R S

    1976-03-01

    A series of experiments, carried out to evaluate the histochemical method for the morphological diagnosis of early stages of myocardial ischaemis (HBFP) is reported. The experiments were performed on dog hearts in which ischaemia was induced by coronary artery ligation for different periods of time. The original procedure or modifications of the HBFP-technique, including different staining, rinsing, and differentiation times, the use of different commercial brands of chemicals and preparatory changes of routine histological procedures such as fixation, embedding, cutting, and mounting, did not give satisfactory results. False positive and negative staining was frequent. Very equivocal results were obtained on serial sections of ischaemic tissue samples. Therefore this method was regarded as unreliable and non-reproducible.

  20. [Endovascular correction of a multi-level arterial lesion in an elderly patient with lower-limb critical ischaemia].

    PubMed

    Ol'shanskiĭ, M S; Esipenko, V V; Ivanov, A A; Moshurov, I P; Kazanskiĭ, D V

    2007-01-01

    Presented herein is a clinical case report showing possibilities of endovascular surgery in comprehensive treatment of a multi-level stenosing lesion in an elderly male patient presenting with pyo-necrotic alterations of the crus and foot. A 67-year-old male patient suffering from diabetes mellitus, lower-limb vessels atherosclerosis, critical ischaemia, indolent wound of the left foot following amputation of the toes was subjected to collaterally approached balloon-mediated angioplasty of critical stenoses of the left common iliac artery and deep femoral artery. During the operation, we used elements of coronary interventions technique. The wound healed completely. Two years after the operation, a good result persists, with the patient being capable of moving unassisted, completely serving himself, and the distance of pain-free walking amounts to more than 150 metres.

  1. Acute rectal obstruction after PPH stapled haemorrhoidectomy.

    PubMed

    Cipriani, S.; Pescatori, M.

    2002-09-01

    An unusual case of acute intestinal obstruction following a PPH stapled haemorrhoidectomy is reported: the complication was due to an almost complete interruption of the rectal lumen tightened by a purse-string suture anchored by staples. The stricture was dilated and the suture released thus restoring intestinal continuity. Surgeons should be aware that such troublesome complication may occur and can be treated successfully by a transanal approach.

  2. 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.

  3. 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.

  4. Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia

    PubMed Central

    White, Robin E; Palm, Curtis; Xu, Lijun; Ling, Evelyn; Ginsburg, Mitchell; Daigle, Bernie J; Han, Ruquan; Patterson, Andrew; Altman, Russ B; Giffard, Rona G

    2012-01-01

    The role of the β2AR (β2 adrenergic receptor) after stroke is unclear as pharmacological manipulations of the β2AR have produced contradictory results. We previously showed that mice deficient in the β2AR (β2KO) had smaller infarcts compared with WT (wild-type) mice (FVB) after MCAO (middle cerebral artery occlusion), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell deaths were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischaemia (Ccl9, Gem and Prg4). In addition to networks that were similar between genotypes, one network with a central core of GPCR (G-protein-coupled receptor) and including biological functions such as carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in β2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype both before and after ischaemia. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice in both sham and MCAO conditions. As both genes are implicated in NF-κB (nuclear factor κB) signalling, we measured p65 activity and TNFα (tumour necrosis factor α) levels 24 h after MCAO. MCAO-induced p65 activation and post-ischaemic TNFα production were both greater in FVB compared with β2KO mice. These results suggest that loss of β2AR signalling results in a neuroprotective phenotype in part due to decreased NF-κB signalling, decreased inflammation and decreased apoptotic signalling in the brain. PMID:22867428

  5. [Use of drug-free methods of treatment in comprehensive therapy of patients with stage II chronic lower limb ischaemia].

    PubMed

    Makarov, I V; Lukashova, A V

    2016-01-01

    Analysed herein are the results of treating a total of 139 patients presenting with stage II chronic lower limb ischaemia. The patients were subdivided into three groups, depending on the variant of treatment performed. Group One patients (n=57) received standard conservative therapy combined with ozone therapy, with the Group being further subdivided into two subgroups: patients of subgroup 1a (n=28) were subjected to intravenous administration of ozonated physiological solution (OPS), subgroup 1b patients (n=29) were given big autohemoozonetherapy (BAT). Group Two patients (n=62) underwent complex treatment including beside medical ozone gravitation therapy (GT). Group Two patients were also subdivided into two subgroups: subgroup 2a patients (n=31) received standard conservative therapy combined with OPS and GT, subgroup 2b patients (n=31) received standard conservative therapy in combination with BAT and GT. Group Three (Control Group) was composed of 20 patients receiving standard conservative therapy alone. The highest efficacy was observed in the subgroup of patients receiving OPS and GT, with the patients of this subgroup showing a statistically significant increase in the pain-free walking distance by 116.5% and in the ankle-brachial index by 49.2%, also demonstrating the most pronounced positive dynamics of lipid metabolism parameters: a decrease in total cholesterol by 21.3%, low density lipoproteins by 25.4%, very low density lipoproteins by 24.2% and triglycerides by 18.5%. Besides, a tendency was observed towards normalization of the haemostasis system indices: fibrinogen decreased by 21.8%, prothrombin index by 13%, fibrin monomer complexes retraction by 18.2%, and the clotting time increased by 20.7%. Hence, combined use of ozonated physiological solution and gravitation therapy in treatment of patients with stage II chronic lower limb ischaemia promotes a considerable increase in the pain-free walking distance and ankle-brachial index, as well as

  6. [Use of drug-free methods of treatment in comprehensive therapy of patients with stage II chronic lower limb ischaemia].

    PubMed

    Makarov, I V; Lukashova, A V

    2016-01-01

    Analysed herein are the results of treating a total of 139 patients presenting with stage II chronic lower limb ischaemia. The patients were subdivided into three groups, depending on the variant of treatment performed. Group One patients (n=57) received standard conservative therapy combined with ozone therapy, with the Group being further subdivided into two subgroups: patients of subgroup 1a (n=28) were subjected to intravenous administration of ozonated physiological solution (OPS), subgroup 1b patients (n=29) were given big autohemoozonetherapy (BAT). Group Two patients (n=62) underwent complex treatment including beside medical ozone gravitation therapy (GT). Group Two patients were also subdivided into two subgroups: subgroup 2a patients (n=31) received standard conservative therapy combined with OPS and GT, subgroup 2b patients (n=31) received standard conservative therapy in combination with BAT and GT. Group Three (Control Group) was composed of 20 patients receiving standard conservative therapy alone. The highest efficacy was observed in the subgroup of patients receiving OPS and GT, with the patients of this subgroup showing a statistically significant increase in the pain-free walking distance by 116.5% and in the ankle-brachial index by 49.2%, also demonstrating the most pronounced positive dynamics of lipid metabolism parameters: a decrease in total cholesterol by 21.3%, low density lipoproteins by 25.4%, very low density lipoproteins by 24.2% and triglycerides by 18.5%. Besides, a tendency was observed towards normalization of the haemostasis system indices: fibrinogen decreased by 21.8%, prothrombin index by 13%, fibrin monomer complexes retraction by 18.2%, and the clotting time increased by 20.7%. Hence, combined use of ozonated physiological solution and gravitation therapy in treatment of patients with stage II chronic lower limb ischaemia promotes a considerable increase in the pain-free walking distance and ankle-brachial index, as well as

  7. Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism, tolerance to ischaemia and preconditioning protection

    PubMed Central

    Rodríguez-Sinovas, Antonio; Sánchez, Jose A; González-Loyola, Alejandra; Barba, Ignasi; Morente, Miriam; Aguilar, Rio; Agulló, Esperanza; Miró-Casas, Elisatet; Esquerda, Neus; Ruiz-Meana, Marisol; García-Dorado, David

    2010-01-01

    Connexin 43 (Cx43) plays an important role in cardioprotective signalling by mechanisms at least in part independent of gap junctional communication. To investigate whether this role is related to specific properties of this connexin isoform, we used a knock-in mouse model in which the coding region of Cx43 is replaced by that of Cx32. Homozygous Cx43KI32 mice showed reduced cell-to-cell Lucifer Yellow transfer (P < 0.01), but QRS duration and left ventricular fractional shortening (echocardiography) were similar to those in wild-type animals. NMR spectroscopy detected reduced ATP and increased lactate content in myocardium from homozygous Cx43KI32 animals (P < 0.05). Despite this, isolated homozygous Cx43KI32 hearts showed smaller infarcts after ischaemia–reperfusion (40 min/60 min) as compared to hearts from heterozygous and wild-type animals (13 and 31% reduction, respectively, P < 0.05). Cardiac myocytes isolated from Cx43KI32 mouse hearts also showed a reduced rate of cell death after simulated ischaemia–reperfusion. In a separate series of experiments, both ischaemic (4 cycles of 3.5 min of ischaemia and 5 min of reperfusion) and pharmacological (50 μmol l−1 diazoxide, 10 min) preconditioning reduced infarct size in hearts from wild-type mice (by 24.84 and 26.63%, respectively, P < 0.05), but only ischaemic preconditioning was effective in hearts from heterozygous animals and both preconditioning strategies failed to protect Cx43KI32 homozygous hearts. These results demonstrate that Cx43 has an important and previously unknown modulatory effect in myocardial energy metabolism and tolerance to ischaemia, and plays a critical role in preconditioning protection, by mechanisms that are specific for this connexin isoform. PMID:20156849

  8. 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.

  9. Current concepts in acute knee dislocation: the missed diagnosis?

    PubMed

    McKee, Lesley; Ibrahim, Mazin S; Lawrence, Trevor; Pengas, Ioannis P; Khan, Wasim S

    2014-01-01

    Traumatic knee dislocation is a serious and potentially limb threatening injury that can be easily missed if meticulous history and examination have not been employed. Neurovascular injuries are common in this condition, and due diligence should be given to their thorough evaluation at time of secondary survey so as to avoid complications such as ischaemia, compartment syndrome and eventual amputation. There is growing evidence in the literature that morbid obesity is associated with low energy knee dislocation, therefore this should be considered when assessing this cohort of patients presenting with an acute knee injury. Early operative intervention especially with multi ligaments involvement is the preferable strategy in the management of this acute injury. Controversy exists whether to reconstruct or repair damaged structures, and whether to adopt a one stage or two stage reconstruction of the cruciate ligaments. Early rehabilitation is important and essential to achieve satisfactory outcomes. This article is an evidence-based overview of this rare but devastating injury.

  10. Walking unsteadily: a case of acute cerebellar ataxia.

    PubMed

    Simonetta, Federico; Christou, Fotini; Vandoni, Riccardo E; Nierle, Thomas

    2013-01-01

    Acute cerebellar ataxia is an infrequent neurological syndrome in adults especially if complicated by additional neurological deficits. We report the case of a 69-year-old woman who presented with sudden onset of left facial droop, dizziness, slurred speech and impaired balance. Her medical history included paroxysmal atrial fibrillation and a sigmoid diverticular abscess treated with ciprofloxacin and metronidazole. Cranial computed tomographic angiography and MRI showed no signs of acute ischaemia or haemorrhage but demonstrated symmetrically distributed lesions in the cerebellar dentate nuclei. A diagnosis of metronidazole-induced encephalopathy was suspected. Metronidazole was stopped and the patient completely recovered. Metronidazole is a commonly prescribed medication. Clinicians should be aware of the clinical and radiological presentation of metronidazole-induced encephalopathy so that this serious but completely reversible condition can be promptly diagnosed. PMID:23283615

  11. Curious case of calciphylaxis leading to acute mitral regurgitation

    PubMed Central

    Gallimore, Grant Gardner; Curtis, Blair; Smith, Andria; Benca, Michael

    2014-01-01

    Calciphylaxis is uncommon and typically seen in patients with end-stage renal disease. It has been defined as a vasculopathic disorder characterised by cutaneous ischaemia and necrosis due to calcification, intimal fibroplasia and thrombosis of pannicular arterioles. We present the case of a 74-year-old woman with chronic kidney disease stage III who developed calciphylaxis leading to mitral valve calcification, chordae tendineae rupture and acute mitral regurgitation. Although an alternative explanation can typically be found for non-uraemic calciphylaxis, her evaluation did not reveal any usual non-uraemic causes including elevated calcium–phosphorus product, hyperparathyroidism, or evidence of connective tissue disease. Her wounds improved with sodium thiosulfate, pamidronate, penicillin and hyperbaric oxygen therapies but she ultimately decompensated with the onset of acute mitral regurgitation attributed to rupture of a previously calcified chordae tendineae. This case highlights an unusual case of calciphylaxis without clear precipitant as well as a novel manifestation of the disease. PMID:24789150

  12. Singing magnets ingestion: a rare cause of intestinal obstruction in children.

    PubMed

    Soomro, Sirajuddin; Mughal, Sikandar Ali

    2014-09-01

    Foreign body ingestion is a common problem in children. Ingested foreign bodies include coins, needles, pins and button batteries. Ingestion of multiple magnets is very rare and poses a unique hazard of intestinal obstruction in children. The ingested magnets may reside in different loops of intestine and attract each other causing necrosis of the intervening wall of intestine. We present the case of a 7-year old child who presented with acute intestinal obstruction due to ingestion of multiple magnets. Patient underwent laparotomy. The loops of small intestine with necrotic walls were found to contain three oblong shaped magnets. Removal of magnets along with resection and anastomosis of affected segment of intestine was performed.

  13. Dai Huang Fu Zi Tang could ameliorate intestinal injury in a rat model of hemorrhagic shock by regulating intestinal blood flow and intestinal expression of p-VASP and ZO-1

    PubMed Central

    2014-01-01

    Background Dai Huang Fu Zi Tang (DHFZT), an oriental herbal formula, has long been used clinically in treatment of intestinal obstruction, acute pancreatitis, cholecystalgia and chronic diarrhea for thousands of years. Recent studies have demonstrated that DHFZT can reduce intestinal pathological injury and the concentration of enterogenous endotoxin in an animal model. But the underlying mechanism has not been fully elucidated. Methods SD male rats in adult were used to model HS and treated with DHFZT. The serum concentration of endotoxin were analyzed by dynamic turbidimetric method. In addition, the blood flow of small intestine were measured using laser speckle technique. Phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) and zonula occludens (ZO)-1 protein, intestinal fatty acid binding protein (IFABP) were measured by Western Blotting, RT-PCR, ELISA respectively. Results Present study showed that DHFZT markedly elevated the blood flow of small intestine, protected the intestinal barrier function by up-regulating the expression of ZO-1 protein and down-regulating expression of p-VASP, and notely decreased serum concentration of IFABP and endotoxin in HS. Conclusions These results reveal that DHFZT improves intestinal blood flow, protects the intestinal barrier function, and ameliorates intestinal endotoxaemia in rats with HS. PMID:24580804

  14. Role of endothelium in ischaemia-induced myocardial dysfunction of isolated working hearts: cardioprotection by activation of adenosine A(2A) receptors.

    PubMed

    Maddock, H L; Broadley, K J; Bril, A; Khandoudi, N

    2001-01-01

    1 This study aimed to determine the role of the vascular endothelium on recovery of contractile function following global low-flow ischaemia of guinea-pig isolated working hearts and the effects of adenosine analogues on this recovery. 2 Guinea-pig isolated spontaneously beating or paced working hearts were set up and coronary flow (CF), aortic output (AO) (as an index of cardiac function), heart rate (HR), left ventricular pressure (LVP) and dP/dt max recorded. The endothelium was either intact or removed by a blast of oxygen. 3 In spontaneously beating hearts, low-flow ischaemia for 30 min reduced CF and cardiac contractility (LVP, dP/dt max) but not AO. On reperfusion, CF, LVP and dP/dt max recovered, while AO fell precipitously followed by a gradual recovery, indicative of myocardial stunning. The effects of ischaemia did not differ between endothelium-intact and -denuded hearts, indicating no role of the endothelium in the changes observed. 4 The adenosine analogues, N6-cyclopentyladenosine (CPA, A1 selective), 5'-N-ethylcarboxamidoadenosine (NECA, two-fold A2 selective over A1) and 2-p-((carboxyethyl)-phenethylamino)-5'carboxamidoadenosine (CGS21680, A2A selective) were infused (3 x 10-7 M) from 10 min into the 30-min low-flow ischaemia of denuded hearts and during reperfusion. 5 CGS21680 increased CF and improved the postischaemic functional recovery, as measured by the AO. NECA and CPA were not cardioprotective. The A2A selective antagonist, ZM241385, attenuated the coronary vasodilatation by CGS21680 and abolished the improved recovery of AO on reperfusion. 6 Reperfusion of paced working hearts caused a dramatic fall in AO which failed to recover. Infusion of CGS21680 from 15 min into the ischaemic period produced vasodilatation but failed to restore AO, presumably because the ischaemic damage was irreversible. 7 Thus, the endothelium plays no role in myocardial dysfunction following low-flow global ischaemia and reperfusion of guinea-pig working hearts

  15. Small Intestinal Infections.

    PubMed

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections. PMID:27168147

  16. Intestinal Rotation Anomalies.

    PubMed

    Pelayo, Juan Carlos; Lo, Andrea

    2016-07-01

    Intestinal rotation abnormality (IRA) predisposes to lethal midgut volvulus. An understanding of intestinal development illustrates the process of normal intestinal rotation and fixation. An appreciation of the clinical presentation and consequences of missed IRA will enhance clinical suspicion and timely evaluation. Selecting the appropriate imaging modality to diagnose IRA requires an understanding of the benefits and limitations of each. The Ladd's procedure continues to be the appropriate surgical treatment for IRA with or without volvulus. Laparoscopy has emerged as an option for the diagnosis and treatment of IRA. Populations in which IRA is always associated, but a Ladd's procedure rarely required, include patients with congenital diaphragmatic hernia and abdominal wall defects. Prevalence of IRA is higher in children with congenital heart disease and heterotaxy syndrome; asymptomatic patients require multidisciplinary consideration of the risks and benefits of screening for IRA, whether a Ladd's procedure is required, and the timing thereof. [Pediatr Ann. 2016;45(7):e247-e250.]. PMID:27403672

  17. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  18. Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development.

    PubMed

    Giammanco, Antonina; Blanc, Valerie; Montenegro, Grace; Klos, Coen; Xie, Yan; Kennedy, Susan; Luo, Jianyang; Chang, Sung-Hee; Hla, Timothy; Nalbantoglu, Ilke; Dharmarajan, Sekhar; Davidson, Nicholas O

    2014-09-15

    HuR is a ubiquitous nucleocytoplasmic RNA-binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur (IKO) mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of Apc(min/+) mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a three-fold decrease in tumor burden characterized by reduced proliferation, increased apoptosis, and decreased expression of transcripts encoding antiapoptotic HuR target RNAs. Similarly, Hur(IKO) mice subjected to an inflammatory colon carcinogenesis protocol [azoxymethane and dextran sodium sulfate (AOM-DSS) administration] exhibited a two-fold decrease in tumor burden. Hur(IKO) mice showed no change in ileal Asbt expression, fecal bile acid excretion, or enterohepatic pool size that might explain the phenotype. Moreover, none of the HuR targets identified in Apc(min/+)Hur(IKO) were altered in AOM-DSS-treated Hur(IKO) mice, the latter of which exhibited increased apoptosis of colonic epithelial cells, where elevation of a unique set of HuR-targeted proapoptotic factors was documented. Taken together, our results promote the concept of epithelial HuR as a contextual modifier of proapoptotic gene expression in intestinal cancers, acting independently of bile acid metabolism to promote cancer. In the small intestine, epithelial HuR promotes expression of prosurvival transcripts that support Wnt-dependent tumorigenesis, whereas in the large intestine epithelial HuR indirectly downregulates certain proapoptotic RNAs to attenuate colitis-associated cancer. Cancer Res; 74(18); 5322-35. ©2014 AACR.

  19. Intestinal β-galactosidases

    PubMed Central

    Gray, Gary M.; Santiago, Nilda A.; Colver, Eugene H.; Genel, Myron

    1969-01-01

    Despite the high prevalence of intestinal lactase deficiency in some racial groups and in patients with intestinal disease, the biochemical defect has not been characterized. In the preceding paper normal intestine was found to have two lactases with distinctly different pH optima. Therefore, pH activity curves of homogenates from lactase-deficient intestine were studied, and the pH optimum was found to be shifted from the normal of 5.8 to 4.8. Density gradient ultracentrifugation of intestinal material from five lactase-deficient patients demonstrated absence of a lactase with pH optimum 6.0 and molecular weight 280,000. A second lactase with pH optimum 4.5 and molecular weights of 156,000 and 660,000 remained at normal levels accounting for the shift in the pH optimum in whole intestinal homogenates. In addition, three of the five patients had absence of a smaller β-galactosidase (molecular weight 80,000) that had specificity only for synthetic substrates. Although not a lactase, this enzyme had a pH optimum identical with the missing lactase, and its activity was inhibited by lactose in a partially competitive manner suggesting that it is capable of binding lactose. It is possible that this enzyme is a precursor or fragment of the missing lactase. The residual lactase activity provided by the lactase with low pH optimum represents 20-70% of the activity of the missing enzyme, and yet these patients are not able to digest dietary lactose. Thus it appears that the residual enzyme plays no significant role in the hydrolysis of ingested lactose. PMID:5774110

  20. Small Intestinal Bacterial Overgrowth

    PubMed Central

    Dukowicz, Andrew C.; Levine, Gary M.

    2007-01-01

    Small intestinal bacterial overgrowth (SIBO), defined as excessive bacteria in the small intestine, remains a poorly understood disease. Initially thought to occur in only a small number of patients, it is now apparent that this disorder is more prevalent than previously thought. Patients with SIBO vary in presentation, from being only mildly symptomatic to suffering from chronic diarrhea, weight loss, and malabsorption. A number of diagnostic tests are currently available, although the optimal treatment regimen remains elusive. Recently there has been renewed interest in SIBO and its putative association with irritable bowel syndrome. In this comprehensive review, we will discuss the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of SIBO. PMID:21960820

  1. Assessment of intestinal malabsorption.

    PubMed

    Nikaki, K; Gupte, G L

    2016-04-01

    Significant efforts have been made in the last decade to either standardize the available tests for intestinal malabsorption or to develop new, more simple and reliable techniques. The quest is still on and, unfortunately, clinical practice has not dramatically changed. The investigation of intestinal malabsorption is directed by the patient's history and baseline tests. Endoscopy and small bowel biopsies play a major role although non-invasive tests are favored and often performed early on the diagnostic algorithm, especially in paediatric and fragile elderly patients. The current clinically available methods and research tools are summarized in this review article.

  2. Assessment of intestinal malabsorption.

    PubMed

    Nikaki, K; Gupte, G L

    2016-04-01

    Significant efforts have been made in the last decade to either standardize the available tests for intestinal malabsorption or to develop new, more simple and reliable techniques. The quest is still on and, unfortunately, clinical practice has not dramatically changed. The investigation of intestinal malabsorption is directed by the patient's history and baseline tests. Endoscopy and small bowel biopsies play a major role although non-invasive tests are favored and often performed early on the diagnostic algorithm, especially in paediatric and fragile elderly patients. The current clinically available methods and research tools are summarized in this review article. PMID:27086887

  3. Intestinal microbiota and ulcerative colitis.

    PubMed

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  4. Small intestine aspirate and culture

    MedlinePlus

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  5. Small intestine contrast injection (image)

    MedlinePlus

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  6. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  7. Updates on antibody-mediated rejection in intestinal transplantation.

    PubMed

    Wu, Guo-Sheng

    2016-09-24

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  8. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.

  9. Successful treatment of a young woman with acute complicated myocardial infarction

    PubMed Central

    Serpytis, Pranas; Kibarskis, Aleksandras; Katkus, Rimgaudas; Samalavicius, Robertas; Glaveskaite, Sigita; Rackauskas, Gediminas

    2013-01-01

    Therapeutic hypothermia is method used to improve the neurological status of patients who are at risk of ischaemia after myocardial infarction. We report a case of a 28-year-old woman who suffered acute myocardial infarction complicated by ventricular fibrillation. The patient was successfully resuscitated. Invasive and non-invasive medical treatment was applied including therapeutic hypothermia. Success was achieved due to adequate public reaction, fast transportation, blood vessel revascularization and application of therapeutic hypothermia. The patient was successfully discharged after one week of treatment, and just minor changes in heart function were present. PMID:24570755

  10. Experience with 123I-iomazenil SPECT in acute cerebral infarction.

    PubMed

    Müller, V; Saur, D; Klutmann, S; Weiller, C; Röther, J; Clausen, M

    2002-12-01

    Neuronal cells are susceptible to cerebral ischaemia. As gamma-aminobutyric acid(A) (GABA(A)) receptors are specific for neurones, functional receptor imaging using I-iomazenil (IMZ), a ligand to the GABA benzodiazepine receptor, has been proposed as an imaging modality for the assessment of neuronal integrity. However, there is only limited experience with IMZ in patients with acute cerebral infarction. Therefore, the aim of this study was to evaluate IMZ single photon emission computed tomography (SPECT) in patients with acute cerebral ischaemia. IMZ SPECT was performed in 21 patients with acute cerebral infarction 7-10 days after stroke onset. Eleven patients underwent systemic thrombolysis within 6 h after symptom onset (group 1), whereas 10 patients were treated conservatively (group 2). IMZ (150-200 MBq) was injected intravenously and imaging was performed using a dedicated four-head SPECT camera at 5 min (perfusion) and 90 min (receptor distribution) post-injection, with an acquisition time of 50 min each. Images were analysed by visual inspection. Four patients showed normal IMZ distribution, and 17 patients showed abnormalities of IMZ uptake on both early and late images. In six patients with regional uptake deficits, a crossed cerebellar diaschisis was observed on early images. Cerebellar inhomogeneity of tracer uptake was absent at the time of late images in all six patients. In eight patients, areas of hypoperfusion corresponded exactly to the regions of receptor deficiency (match). In five patients, preserved neuronal integrity was present in hypoperfused areas (mismatch). In four patients, normally or even hyperperfused areas exhibited regional receptor deficiency (inverse mismatch). In conclusion, IMZ SPECT demonstrated differences between regional perfusion and receptor distribution in about one-half of patients 7-10 days after acute cerebral ischaemia. Interesting patterns between the early phase (perfusion) and the late phase (receptor

  11. 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.

  12. Small Intestine Cancer Treatment

    MedlinePlus

    ... small intestine cancer include unexplained weight loss and abdominal pain. These and other signs and symptoms may be ... doctor if you have any of the following: Pain or cramps in the middle of the abdomen. Weight loss with no known reason. A lump ...

  13. Small intestinal fungal overgrowth.

    PubMed

    Erdogan, Askin; Rao, Satish S C

    2015-04-01

    Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear but small intestinal dysmotility and use of proton pump inhibitors has been implicated. However, further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth, both in healthy subjects and in patients with otherwise unexplained GI symptoms. Importantly, whether eradication or its treatment leads to resolution of symptoms remains unclear; at present, a 2-3-week course of antifungal therapy is recommended and may be effective in improving symptoms, but evidence for eradication is lacking. PMID:25786900

  14. Aging and the intestine

    PubMed Central

    Drozdowski, Laurie; Thomson, Alan BR

    2006-01-01

    Over the lifetime of the animal, there are many changes in the function of the body’s organ systems. In the gastrointestinal tract there is a general modest decline in the function of the esophagus, stomach, colon, pancreas and liver. In the small intestine, there may be subtle alterations in the intestinal morphology, as well as a decline in the uptake of fatty acids and sugars. The malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2) or dexamethasone. Modifications in the type of lipids in the diet will influence the intestinal absorption of nutrients: for example, in mature rats a diet enriched with saturated as compared with polysaturated fatty acids will enhance lipid and sugar uptake, whereas in older animals the opposite effect is observed. Thus, the results of studies of the intestinal adaptation performed in mature rats does not necessarily apply in older animals. The age-associated malabsorption of nutrients that occurs with aging may be one of the several factors which contribute to the malnutrition that occurs with aging. PMID:17171784

  15. Hepatic and Intestinal Schistosomiasis: Review

    PubMed Central

    Elbaz, Tamer; Esmat, Gamal

    2013-01-01

    Schistosomiasis is an endemic disease in Egypt caused by the trematode Schistosoma which has different species. Hepatic schistosomiasis represents the best known form of chronic disease with a wide range of clinical manifestations. The pathogenesis of schistosomiasis is related to the host cellular immune response. This leads to granuloma formation and neo angiogenesis with subsequent periportal fibrosis manifested as portal hypertension, splenomegaly and esophageal varices. Intestinal schistosomiasis is another well identified form of chronic schistosomal affection. Egg deposition and granuloma formation eventually leads to acute then chronic schistosomal colitis and is commonly associated with polyp formation. It frequently presents as abdominal pain, diarrhea, tenesmus and anal pain. Definite diagnosis of schistosomiasis disease depends on microscopy and egg identification. Marked progress regarding serologic diagnosis occurred with development of recent PCR techniques that can confirm schistosomal affection at any stage. Many antischistosomal drugs have been described for treatment, praziquantel being the most safe and efficient drug. Still ongoing studies try to develop effective vaccines with identification of many target antigens. Preventive programs are highly needed to control the disease morbidity and to break the cycle of transmission. PMID:25685451

  16. The role of small intestinal bacterial overgrowth in Parkinson's disease.

    PubMed

    Fasano, Alfonso; Bove, Francesco; Gabrielli, Maurizio; Petracca, Martina; Zocco, Maria Assunta; Ragazzoni, Enzo; Barbaro, Federico; Piano, Carla; Fortuna, Serena; Tortora, Annalisa; Di Giacopo, Raffaella; Campanale, Mariachiara; Gigante, Giovanni; Lauritano, Ernesto Cristiano; Navarra, Pierluigi; Marconi, Stefano; Gasbarrini, Antonio; Bentivoglio, Anna Rita

    2013-08-01

    Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society. PMID:23712625

  17. The role of small intestinal bacterial overgrowth in Parkinson's disease.

    PubMed

    Fasano, Alfonso; Bove, Francesco; Gabrielli, Maurizio; Petracca, Martina; Zocco, Maria Assunta; Ragazzoni, Enzo; Barbaro, Federico; Piano, Carla; Fortuna, Serena; Tortora, Annalisa; Di Giacopo, Raffaella; Campanale, Mariachiara; Gigante, Giovanni; Lauritano, Ernesto Cristiano; Navarra, Pierluigi; Marconi, Stefano; Gasbarrini, Antonio; Bentivoglio, Anna Rita

    2013-08-01

    Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

  18. Measurement of small intestinal damage.

    PubMed

    Takeuchi, Koji; Satoh, Hiroshi

    2010-08-01

    Many animal models have been devised for investigating the pathogenesis of intestinal lesions and for screening drugs for the treatment of intestinal ulcers in humans. Recently, particular attention has been focused on NSAID-induced intestinal lesions as a result of the development of the capsule endoscope and double-balloon endoscope. Ischemic enteritis, one of the most dramatic abdominal emergencies, is known to cause severe damage to the small intestine by a significant decrease of arterial blood flow in the small intestine. In this unit, two animal models for small intestinal damage induced by NSAIDs or intestinal ischemia are described. Also included are methods for lesion induction and evaluation of the damage as well as the measurement of pathogenic functional and biochemical changes.

  19. A rare cause of mechanical obstruction: Intestinal myeloid sarcoma

    PubMed Central

    Yoldaş, Tayfun; Erol, Varlık; Demir, Batuhan; Hoşcoşkun, Cüneyt

    2014-01-01

    Myeloid sarcoma is a rare aggressive tumour that originates from immature extramedullary myeloid cells. It can be seen as a relapse in patients with acute myeloid leukaemia. Sometimes it can be seen in the form of a solid tumour without any evidence of leukaemia. A case of a 44-year-old male patient who was admitted with symptoms and signs of mechanical intestinal bowel obstruction was operated on. The operation findings showed small bowel obstruction due to a mass. The mass was then resected with end-to-end intestinal anastomosis. The resected mass pathology results were consistent with myeloid sarcoma. The post-operative period was uneventful and adjuvant therapy was applied. In this case report we aimed to evaluate the clinical signs and treatment modalities of small intestinal myeloid sarcoma. PMID:25931908

  20. Multiple targets of carbon monoxide gas in the intestinal inflammation.

    PubMed

    Naito, Yuji; Takagi, Tomohisa; Uchiyama, Kazuhiko; Katada, Kazuhiro; Yoshikawa, Toshikazu

    2016-04-01

    Inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease are chronic relapsing and remitting inflammatory disorders of the intestinal tract. It is important to investigate the precise pathogenesis of IBD, to evaluate new anti-inflammatory agents, and to develop novel drugs. Carbon monoxide (CO) has emerged as an important regulator of acute and chronic inflammation of the gastrointestinal tract. The mechanism underlying its anti-inflammatory effects is only partially understood. Recent reports have demonstrated that CO could play a role in the functional modulation of epithelial and immunological cells in the intestine. In this short review, we have highlighted the recent findings that CO stimulates the epithelial cell restitution and FGF production from myofibroblasts. CO was also shown to regulate T cell activation and differentiation, and to activate macrophages. Finally, we have discussed the direction of translational research with respect to launching a novel agent for releasing CO in the intestine.

  1. [Acute pancreatitis and pregnancy].

    PubMed

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery.

  2. Crohn's disease and acute pancreatitis. A review of literature.

    PubMed

    Jasdanwala, Sarfaraz; Babyatsky, Mark

    2015-03-01

    Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  3. Plasma exchange in small intestinal transplantation between ABO-incompatible individuals: A case report

    PubMed Central

    ZHANG, QIUHUI; HU, XINGBIN; XIA, AIJUN; YI, JING; AN, QUNXING; ZHANG, XIANQING

    2014-01-01

    The aim of this study was to investigate the application of plasma exchange in small intestinal transplantation between ABO blood type-incompatible patients. A small intestinal transplantation case between ABO-incompatible individuals is hereby presented and analyzed. The main treatment included plasma exchange, splenectomy and immunosuppression. The patient undergoing small intestinal transplantation exhibited stable vital signs. A mild acute rejection reaction developed ~2 weeks after the surgery, which the patient successfully overcame. The subsequent colonoscopy and pathological examination revealed no signs of acute rejection. In conclusion, plasma exchange in combination with anti-immune rejection therapy proved to be an effective scheme for the management of small intestinal transplantation between ABO-incompatible patients. PMID:24649066

  4. Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway.

    PubMed

    Ghadernezhad, Negar; Khalaj, Leila; Pazoki-Toroudi, Hamidreza; Mirmasoumi, Masoumeh; Ashabi, Ghorbangol

    2016-10-01

    Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia. Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory. Materials and methods Rats were pretreated with metformin (200 mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured. Results Pretreatment with metformin (met) in the met + ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p < 0.001) and increased latency time compared with the I/R group (p < 0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R + met group (p < 0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p < 0.001) but increased that compared with the sham group (p < 0.001). The level of pro-BDNF decreased in the met + CC + I/R group compared with the met + I/R group (p < 0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p < 0.001). Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.

  5. 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.

  6. Intestinal sensing of nutrients.

    PubMed

    Tolhurst, Gwen; Reimann, Frank; Gribble, Fiona M

    2012-01-01

    Ingestion of a meal triggers a range of physiological responses both within and outside the gut, and results in the remote modulation of appetite and glucose homeostasis. Luminal contents are sensed by specialised chemosensitive cells scattered throughout the intestinal epithelium. These enteroendocrine and tuft cells make direct contact with the gut lumen and release a range of chemical mediators, which can either act in a paracrine fashion interacting with neighbouring cells and nerve endings or as classical circulating hormones. At the molecular level, the chemosensory machinery involves multiple and complex signalling pathways including activation of G-protein-coupled receptors and solute carrier transporters. This chapter will discuss our current knowledge of the molecular mechanisms underlying intestinal chemosensation with a particular focus on the relatively well-characterised nutrient-triggered secretion from the enteroendocrine system. PMID:22249821

  7. Elenoside increases intestinal motility

    PubMed Central

    Navarro, E; Alonso, SJ; Navarro, R; Trujillo, J; Jorge, E

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10-4, 6.4 x 10-4 and 1.2 x 10-3 mol/L, and cisapride at 10-6 mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain. PMID:17131476

  8. A human model of platelet–leucocyte adhesive interactions during controlled ischaemia in patients with peripheral vascular disease

    PubMed Central

    Pasqualini, L; Pirro, M; Lombardini, R; Ciuffetti, G; Dragani, P; Mannarino, E

    2002-01-01

    Aims: In humans, little is known about the effects of platelet–leucocyte interactions on blood viscosity and microvascular perfusion. This study tested the hypotheses that (1) activation and interactions between platelets and leucocytes may have an impact on microvascular blood viscosity and perfusion in patients with stage II peripheral arterial occlusive disease, and (2) a powerful antiplatelet drug such as Clopidogrel might help to improve microvascular perfusion by reducing platelet–leucocyte activation and blood viscosity. Methods: Plasma concentrations of certain markers of leucocyte and platelet activation, in addition to low and high shear rate blood viscosity, were measured before and after a repeated exercise treadmill test. Functional parameters including maximum walking time, transcutaneous oxygen pressure, and half recovery time were also measured. Results: Blocking platelet activation only with a single dose of Clopidogrel (300 mg) did not improve microvascular blood viscosity and perfusion after repeated exercise, but a significant improvement in microvascular perfusion during controlled ischaemia and a lack of post exercise increase in low shear rate blood viscosity was achieved when both platelet and leucocyte activation were suppressed by a relatively longer treatment with Clopidogrel (four days). Conclusions: Clopidogrel, by inhibiting platelet activation and aggregation, might also block the vicious cycle of leucocyte–platelet activation, thus improving the functioning of the microcirculation. PMID:12461065

  9. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.

    PubMed

    Lopes, Rosana S; Cardoso, Marcelo M; Sampaio, Arthur O; Barbosa, Mario Santos; Souza, Celice C; DA Silva, Michelle C; Ferreira, Elane Magno N; Freire, Marco Aurelio M; Lima, Rafael Rodrigues; Gomes-Leal, Walace

    2016-09-01

    Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke. PMID:27581930

  10. Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia

    PubMed Central

    Deng, Yuxiao; Yang, Zhongwei; Terry, Toya; Pan, Su; Woodside, Darren G.; Wang, Jingxiong; Ruan, Kehe; Willerson, James T.; Dixon, Richard A. F.; Liu, Qi

    2016-01-01

    Promoting the paracrine effects of human mesenchymal stem cell (hMSC) therapy may contribute to improvements in patient outcomes. Here we develop an innovative strategy to enhance the paracrine effects of hMSCs. In a mouse hindlimb ischaemia model, we examine the effects of hMSCs in which a novel triple-catalytic enzyme is introduced to stably produce prostacyclin (PGI2-hMSCs). We show that PGI2-hMSCs facilitate perfusion recovery and enhance running capability as compared with control hMSCs or iloprost (a stable PGI2 analogue). Transplanted PGI2-hMSCs do not incorporate long term into host tissue, but rather they mediate host regeneration and muscle mass gain in a paracrine manner. Mechanistically, this involves long noncoding RNA H19 in promoting PGI2-hMSC-associated survival and proliferation of host progenitor cells under hypoxic conditions. Together, our data reveal the novel ability of PGI2-hMSCs to stimulate host regenerative processes and improve physical function by regulating long noncoding RNA in resident progenitor cells. PMID:27080438

  11. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  12. Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation

    PubMed Central

    Bourke, Lauren; McCormick, James; Taylor, Valerie; Pericleous, Charis; Blanchet, Benoit; Costedoat-Chalumeau, Nathalie; Stuckey, Daniel; Lythgoe, Mark F.; Stephanou, Anastasis; Ioannou, Yiannis

    2015-01-01

    An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R) injury. This study investigated the role of hydroxychloroquine (HCQ) in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2. PMID:26636577

  13. Suppression of ischaemia-induced injuries in rat brain by protease-activated receptor-1 (PAR-1) activating peptide.

    PubMed

    Zhen, Xia; Ng, Ethel Sau Kuen; Lam, Francis Fu Yuen

    2016-09-01

    Ischaemic stroke has become one of the leading causes of death and disability worldwide. The role of protease activated receptor-1 (PAR-1) in this disease is uncertain. In the present study, the actions of a protease activated receptor-1 activating peptide (PAR-1 AP) SFLLRN-NH2 were investigated in an in vivo rat model of ischaemic stroke induced by middle cerebral artery occlusion (MCAO) and in an in vitro model induced by oxygen and glucose deprivation (OGD) in primary cultured rat embryonic cortical neurones. Rats subjected to MCAO exhibited increased brain infarct volume, oedema, and neurological deficit. Rat cortical neurones subjected to OGD showed increased lactate dehydrogenase, caspase-3 activity and TUNEL positive cells, whereas, mitochondrial membrane potential and cell viability were decreased. Furthermore, both models had elevated levels of reactive oxygen species, nitrite, and malondialdehyde, while anti-oxidant enzymes and bcl-2/bax ratio were decreased. These detrimental changes were suppressed by SFLLRN-NH2, and its protective actions were inhibited by a PAR-1 antagonist (BMS-200261). In summary, SFLLRN-NH2 was found to possess anti-oxidant and anti-apoptotic properties, and it produced marked inhibition on the detrimental effects of ischaemia in in vivo and in vitro models of ischaemic stroke. The present findings suggest PAR-1 is a promising target for development of novel treatments of ischaemic brain disease. PMID:27238976

  14. The allometry of rodent intestines.

    PubMed

    Lovegrove, Barry G

    2010-06-01

    This study examined the allometry of the small intestine, caecum, colon and large intestine of rodents (n = 51) using a phylogenetically informed approach. Strong phylogenetic signal was detected in the data for the caecum, colon and large intestine, but not for the small intestine. Most of the phylogenetic signal could be attributed to clade effects associated with herbivorous versus omnivorous rodents. The herbivorous rodents have longer caecums, colons and large intestines, but their small intestines, with the exception of the desert otomyine rodents, are no different to those of omnivorous rodents. Desert otomyine rodents have significantly shorter small intestines than all other rodents, reflecting a possible habitat effect and providing a partial explanation for the low basal metabolic rates of small desert mammals. However, the desert otomyines do not have shorter colons or large intestines, challenging claims for adaptation to water retention in arid environments. Data for the Arvicolidae revealed significantly larger caecums and colons, and hence longer large intestines, with no compensatory reduction in the length of the small intestine, which may explain how the smallest mammalian herbivores manage to meet the demands of a very high mass-specific metabolic rate. This study provides phylogenetically corrected allometries suitable for future prediction testing.

  15. Alcohol and the Intestine.

    PubMed

    Patel, Sheena; Behara, Rama; Swanson, Garth R; Forsyth, Christopher B; Voigt, Robin M; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches.

  16. Alcohol and the Intestine

    PubMed Central

    Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

  17. Alcohol and the Intestine.

    PubMed

    Patel, Sheena; Behara, Rama; Swanson, Garth R; Forsyth, Christopher B; Voigt, Robin M; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

  18. Intestinal bacteria and ageing.

    PubMed

    Woodmansey, E J

    2007-05-01

    Advancements in science and medicine, as well as improved living standards, have led to a steady increase in life expectancy, and subsequently a rise in the elderly population. The intestinal microbiota is important for maintenance of host health, providing energy, nutrients and protection against invading organisms. Although the colonic microbiota is relatively stable throughout adult life, age-related changes in the gastrointestinal (GI) tract, as well as changes in diet and host immune system reactivity, inevitably affect population composition. Recent studies indicate shifts in the composition of the intestinal microbiota, which may lead to detrimental effects for the elderly host. Increased numbers of facultative anaerobes, in conjunction with a decrease in beneficial organisms such as the anaerobic lactobacilli and bifidobacteria, amongst other anaerobes, have been reported. These changes, along with a general reduction in species diversity in most bacterial groups, and changes to diet and digestive physiology such as intestinal transit time, may result in increased putrefaction in the colon and a greater susceptibility to disease. Therapeutic strategies to counteract these changes have been suggested in ageing people. These include dietary supplements containing prebiotics, probiotics and a combination of both of these, synbiotics. Limited feeding trials show promising results with these supplements, although further longer-term investigations are required to substantiate their use in elderly healthcare fields. PMID:17448153

  19. [Maintenance of intestinal barrier function in patients with chronic critical illness].

    PubMed

    Wu, Xiuwen; Ren, Jianan; Li, Jieshou

    2016-07-01

    The syndrome known as chronic critical illness (CCI) is defined as that critically ill patients survive their initial acute illness but go on to experience persistent organ failures necessitating prolonged intensive care. Intestinal barrier is the physical barrier that separates the internal and external environments and prevents the invasion of pathogenic antigens. Due to its pathogenesis, many CCI patients have injured intestinal barrier. Gut is the motor organ of stress responses, and gut-associated infections may initiate multiple organ dysfunction. In this way, it is important to maintain intestinal barrier of such patients. Apart from treatment for underlying diseases, resuscitation aiming at improving tissue perfusion, appropriate nutritional support, protection of normal intestinal flora, and provision of probiotics can maintain intestinal barrier of CCI patients. The maintenance and support of barrier function requires attention. PMID:27452748

  20. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells

    PubMed Central

    Benakis, Corinne; Brea, David; Caballero, Silvia; Faraco, Giuseppe; Moore, Jamie; Murphy, Michelle; Sita, Giulia; Racchumi, Gianfranco; Ling, Lilan; Pamer, Eric G.; Iadecola, Costantino; Anrather, Josef

    2016-01-01

    Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduces ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine leading to an increase in regulatory T cells and a reduction in IL-17+ γδ T cells, through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Interleukin-10 (IL-10) and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and the impact of the intestinal flora and meningeal IL-17+ γδ T cells on ischemic injury. PMID:27019327

  1. Programmed necrosis in acute kidney injury.

    PubMed

    Linkermann, Andreas; De Zen, Federica; Weinberg, Joel; Kunzendorf, Ulrich; Krautwald, Stefan

    2012-09-01

    Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-dependent necroptosis causes organ failure following stroke, myocardial infarction and renal ischaemia/reperfusion injury. Necroptosis can be mediated either by a large intracellular caspase-8-containing signalling complex called the ripoptosome or by the RIP1-/RIP3-containing necroptosome and is controlled by a caspase-8/FLICE inhibitory protein(long) heterodimer at least in the latter case. Second, mitochondrial permeability transition mediates apoptotic or necrotic stimuli and depends on the mitochondrial protein cyclophilin D. The third PN pathway involves the poly(ADP-ribose) polymerase-calpain axis that contributes to acute kidney injury (AKI). Preclinical interference with the PN pathways therefore raises expectations for the future treatment of ischaemic conditions. In this brief review, we aim to summarize the clinically relevant PCD pathways and to transfer the basic science data to settings of AKI. We conclude that pathologists were quite right to refer to ischaemic kidney injury as 'acute tubular necrosis'. PMID:22942173

  2. Microbes, intestinal inflammation and probiotics.

    PubMed

    Khan, Mohammad W; Kale, Amod A; Bere, Praveen; Vajjala, Sriharsha; Gounaris, Elias; Pakanati, Krishna Chaitanya

    2012-02-01

    Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic balance among the intestinal immune compartment, epithelium and microbiota. Owing to the emergence of IBD as a major cause of morbidity and mortality, great efforts have been put into understanding the sequence of intestinal inflammatory events. Intestinal macrophages and dendritic cells act in a synergistic fashion with intestinal epithelial cells and microbiota to initiate the triad that governs the intestinal immune responses (whether inflammatory or regulatory). In this review, we will discuss the interplay of intestinal epithelial cells, bacteria and the innate immune component. Moreover, whether or not genetic intervention of probiotic bacteria is a valid approach for attenuating/mitigating exaggerated inflammation and IBD will also be discussed.

  3. [Surgical treatment of primary multiple tumoral lesions of the large intestine].

    PubMed

    Todurov, I M; Belianskiĭ, L S; Perekhrestenko, A V

    2008-03-01

    Experience of treatment of 37 patients, suffering primarily-multiple cancer of large intestine, including 17--with synchronous and 20--metachronous tumors, and an acute obturational ileus of large intestine, is presented. There was conducted the analysis and peculiarities of surgical tactics suggested as well as various methods of such patients treatment were determined. The investigation results trust the necessity of application of individual perioperative tactics in patients, suffering primarily-multiple tumors of large intestine leading to achieve better outcomes of their surgical treatment.

  4. A Case of Idiopathic Mesenteric Phlebosclerosis with Progressive Intestinal Necrosis.

    PubMed

    Kayano, Hajime; Nomura, Eiji; Hiraiwa, Shinichiro; Kuramoto, Toru; Yatabe, Kentaro; Machida, Takashi; Tajiri, Takuma; Mukai, Masaya; Makuuchi, Hiroyasu

    2016-01-01

    The patient was a 39-year-old woman who was referred to our department from her previous doctor with a 2-day history of right abdominal pain. Abdominal computed tomography showed wall thickening associated with calcification in the ascending colon. Contrast enhancement in the same portion of the intestinal wall was rather poor. Fluid accumulation was also seen around the intestine, so emergency surgery was performed under a provisional diagnosis of intestinal necrosis. Intestinal necrosis due to idiopathic mesenteric phlebosclerosis was diagnosed from postoperative histopathological tests. Idiopathic mesenteric phlebosclerosis displays a chronic course and in most cases conservative treatment is indicated. Bowel obstruction is common among patients who require surgical treatment, but rare cases such as the present one are also seen in which intestinal necrosis occurs. In recent years, an association with herbal medicine has been indicated as one potential cause of this disease, and this entity should be kept in mind when patients with acute abdomen and a history of taking herbal medicines are encountered. PMID:27344996

  5. Intestinal Pseudoobstruction Caused by Chronic Lyme Neuroborreliosis. A Case Report.

    PubMed

    Schefte, David F; Nordentoft, Tyge

    2015-07-30

    Chronic intestinal pseudoobstruction is often classified as idiopathic. The condition is associated with poor quality of life and high morbidity, and treatment options are often unsatisfactory. A case of chronic intestinal pseudoobstruction in a 66-year-old woman, presenting with back and abdominal pain, urinary retention and severe constipation is described. The patient lived in an area in which Lyme disease is endemic and had been bitten by ixodes ticks. Intrathecal synthesis of anti-borrelia IgM and IgG and lymphocytosis in the cerebrospinal fluid was found, consistent with chronic Lyme neuroborreliosis since symptoms had lasted for more than six months. The patient's gastrointestinal function recovered and the pain subsided significantly following treatment with antibiotics. Lyme neuroborreliosis (LNB) often results in palsy, but rarely affects the autonomic nervous system. Three patients have been described with intestinal pseudoobstruction due to acute LNB. However, this is the first described case of intestinal pseudoobstruction due to chronic Lyme neuroborreliosis. LNB must be suspected in patients with intestinal pseudoobstruction, in particular in patients who have been bitten by an ixodes tick and in patients living in an endemic area. PMID:26130639

  6. Myocardial ischaemia and the inflammatory response: release of heat shock protein 70 after myocardial infarction

    PubMed Central

    Dybdahl, B; Slørdahl, S A; Waage, A; Kierulf, P; Espevik, T; Sundan, A

    2005-01-01

    Objectives: To test the hypothesis that heat shock protein (Hsp) 70 may be released into the circulation after acute myocardial infarction (AMI) by exploring the kinetics of Hsp70 release and the relations between Hsp70 and markers of inflammation and myocardial damage in AMI. Design: Blood samples from 24 patients were prospectively collected through to the first day after AMI. Hsp70, interleukin (IL) 6, IL-8, and IL-10 in serum were measured by enzyme linked immunosorbent assay (ELISA). Results: Median Hsp70 concentrations in AMI patients measured at arrival, six hours thereafter, and the following morning were 686, 868, and 607 pg/ml, respectively. These concentrations were all significantly different from those of the control patients with angina with a median serum Hsp70 concentration of 306 pg/ml. Peak Hsp70 correlated with creatine kinase (CK) MB (r  =  0.62, p < 0.01) and cardiac troponin T (r  =  0.58, p < 0.01). Furthermore, serum Hsp70 correlated with IL-6 and IL-8 at six hours (r  =  0.60, p < 0.01 and r  =  0.59, p < 0.01, respectively). Conclusions: In this study, Hsp70 was rapidly released into the circulation after AMI. Circulating Hsp70 is suggested as a marker of myocardial damage. In addition, Hsp70 may have a role in the inflammatory response after AMI. PMID:15710705

  7. Focal cerebral ischaemia induces a decrease in activity and a shift in ouabain affinity of Na+, K+-ATPase isoforms without modifications in mRNA and protein expression.

    PubMed

    Jamme, I; Barbey, O; Trouvé, P; Charlemagne, D; Maixent, J M; MacKenzie, E T; Pellerin, L; Nouvelot, A

    1999-02-20

    In a mouse model of focal cerebral ischaemia, we observed after 1 h of ischaemia, that the total Na+, K+-ATPase activity was decreased by 39.4%, and then did not vary significantly up to 6 h post-occlusion. In the sham group, the dose-response curves for ouabain disclosed three inhibitory sites of low (LA), high (HA) and very high (VHA) affinity. In ischaemic animals, we detected the presence of only two inhibitory sites for ouabain. After 1 h of permanent occlusion, the first site exhibited a low affinity while the second site presented an affinity intermediate between those of HA and VHA sites, which evolved after 3 h and 6 h of occlusion towards that of the VHA site. The presence of only two ouabain sites for Na+, K+-ATPase after ischaemia could result from a change in ouabain affinity of both HA and VHA sites (alpha2 and alpha3 isoforms, respectively) to form a unique component. Irrespective of the duration of ischaemia, the smaller activity of this second site accounted entirely for the loss in total activity. Surprisingly, no modifications in protein and mRNA expression of any alpha or beta isoforms of the enzyme were observed, thus suggesting that ischaemia could induce intrinsic modifications of the Na+, K+-ATPase. PMID:10082868

  8. Microcirculatory detection of Toll-like receptor 4 in rat pancreas and intestine.

    PubMed

    Li, Yuan; Zhou, Zong-Guang; Zhang, Jie; Chen, You-Dai; Li, Hong-Guang; Gao, Hong-Kai; Wang, Rong; Hu, Ting-Ze

    2006-01-01

    This paper was aimed to detect Toll-like receptor 4 (TLR4) microcirculatory expression and localization in rat pancreas and intestine. Acute pancreatitis (AP) was induced by twice injections of cerulein (20 mug in total) and acute necrotizing pancreatitis (ANP) was induced by intraductal injection of 5% taurocholate (1 ml/kg.bw). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to detect and localize TLR4 in the pancreas and intestine. Results showed that RT-PCR of RNA isolated from pancreatic and intestinal tissue yielded the predicted amplicon for TLR4; IHC analysis localized TLR4 expression to the endothelium of pancreatic arteriole, venule, acinar capillary network and sinusoidal capillary of endocrine islet; TLR4 expression in intestine was principally in the microvascular endothelium and leucocytes within the mucosa lamina propria. TLR4 staining in intestine was more intense in taurocholate-induced pancreatitis (TIP) than that in cerulein-induced pancreatitis (CIP). In conclusion, TLR4 could be detected in the pancreatic and intestinal microcirculation, suggesting TLR4 involved in the microcirculatory impairment in AP; the more intense intestinal TLR4 expression in TIP suggests a potential risk for secondary infection.

  9. Paneth cell-mediated multiorgan dysfunction after acute kidney injury

    PubMed Central

    Park, Sang Won; Kim, Mihwa; Kim, Joo Yun; Ham, Ahrom; Brown, Kevin M.; Mori-Akiyama, Yuko; Ouellette, André J.; D’Agati, Vivette D.; Lee, H. Thomas

    2012-01-01

    Acute kidney injury (AKI) is frequently complicated by extra-renal multi-organ injury including intestinal and hepatic dysfunction. In this study, we hypothesized that a discrete intestinal source of pro-inflammatory mediators drives multi-organ injury in response to AKI. After induction of AKI in mice by renal ischemia-reperfusion or bilateral nephrectomy, small intestinal Paneth cells increased the synthesis and release of IL-17A in conjunction with severe intestinal apoptosis and inflammation. We also detected significantly increased IL-17A in portal and systemic circulation after AKI. Intestinal macrophages appear to transport released Paneth cell granule constituents induced by AKI, away from the base of the crypts into the liver. Genetic or pharmacologic depletion of Paneth cells decreased small intestinal IL-17A secretion and plasma IL-17A levels significantly and attenuated intestinal, hepatic, and renal injury after AKI. Similarly, portal delivery of IL-17A in macrophage depleted mice decreased markedly, and intestinal, hepatic, and renal injury following AKI was attenuated without affecting intestinal IL-17A generation. In conclusion, AKI induces IL-17A synthesis and secretion by Paneth cells to initiate intestinal and hepatic injury by hepatic and systemic delivery of IL-17A by macrophages. Modulation of Paneth cell dysregulation may have therapeutic implications by reducing systemic complications arising from AKI. PMID:23109723

  10. Targeting Iron Homeostasis in Acute Kidney Injury.

    PubMed

    Walker, Vyvyca J; Agarwal, Anupam

    2016-01-01

    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

  11. Acute Anteroseptal Myocardial Infarction after a Negative Exercise Stress Test.

    PubMed

    Al-Alawi, Abdullah M; Janardan, Jyotsna; Peck, Kah Y; Soward, Alan

    2016-05-01

    A myocardial infarction is a rare complication which can occur after an exercise stress test. We report a 48-year-old male who was referred to the Mildura Cardiology Practice, Victoria, Australia, in August 2014 with left-sided chest pain. He underwent an exercise stress test which was negative for myocardial ischaemia. However, the patient presented to the Emergency Department of the Mildura Base Hospital 30 minutes after the test with severe retrosternal chest pain. An acute anteroseptal ST segment elevation myocardial infarction was observed on electrocardiography. After thrombolysis, he was transferred to a tertiary hospital where coronary angiography subsequently revealed significant left anterior descending coronary artery stenosis. Thrombus aspiration and a balloon angioplasty were performed. The patient was discharged three days after the surgical procedure in good health.

  12. Management of cardiogenic shock complicating acute myocardial infarction.

    PubMed

    Van Herck, Jozef L; Claeys, Marc J; De Paep, Rudi; Van Herck, Paul L; Vrints, Christiaan J; Jorens, Philippe G

    2015-06-01

    Cardiogenic shock complicates approximately 5-10% of cases with acute myocardial infarction and carries a poor prognosis. Early revascularization remains the cornerstone treatment of cardiogenic shock complicating myocardial infarction. Inotropic and/or vasopressor agents can be used for haemodynamic stabilization, although this comes at the expense of increased myocardial oxygen consumption and extended myocardial ischaemia. In recent years, the use of mechanical circulatory support has significantly increased. However, there is only limited data available from randomized trials evaluating the different percutaneous support systems. This review summarizes the available literature concerning the management of cardiogenic shock and gives an overview of the recommendations of the European and German-Austrian guidelines on cardiogenic shock.

  13. Avicenna’s View on the Etiologies of Intestinal Obstruction

    PubMed Central

    Moradi, Zahra; Besharat, Mehdi; Minaiee, Bagher; Aliasl, Jale; Parsa Yekta, Zohreh; Nasiri Toosi, Mohsen

    2016-01-01

    Context: Bowel obstruction is one of the most common causes of acute abdomen. Because of heterogeneity of patients’ population and variety of causes, therapeutic strategies are not standardized, so treatment of intestinal obstruction is a surgical challenge in many cases. A traditional medicine approach could help detect some issues that were ignored by modern medicine. One of the major schools of medicine, with a history of several thousand years, is Iranian traditional medicine. In this regard, Avicenna, who lived in the medieval period, has had a great influence on the medical knowledge of the world by writing an encyclopedia of medicine entitled “Qanun of Medicine.” Evidence Acquisition: The aim of this study was to investigate Avicenna’s views on the causes of intestinal obstruction and comparing them to modern medicine views. This is a review study on an Iranian traditional textbook of medicine by Avicenna, entitled “Qanun of Medicine” (in short “Qanun”). We used Qanun in its original language (Arabic) along with its Persian translation. It consists of 5 books. Part 16 of the third book talks about intestinal anatomy and introduces some intestinal diseases such as “qoolinj” and “ilavos.” Intestinal obstruction can be a kind of “qoolinj” or “ilavos” disease. All intestinal obstruction etiologies in Qanun are searched in international and Iranian databases (Scopus, ISI, SID, and Iranmedex) and similar causes in modern medicine will be discussed in this article. Results: According to Qanun, 16 causes are involved in intestinal etiologies of bowel obstruction such as “reeh,” mucoid phlegm, abdominal hot and dry distemperament, decreased bile secretion, job, and so on while modern medicine considers some of them, for instance, volvulus, intestinal herniation, worm, intestinal pseudo-obstruction, and opiate. Conclusions: Attention to the similar causes of intestinal obstruction in modern medicine and traditional medicine is the

  14. Mucosal Immunity and acute viral gastroenteritis.

    PubMed

    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.

  15. Intestinal transplantation in children with chronic intestinal pseudo-obstruction

    PubMed Central

    Sigurdsson, L; Reyes, J; Kocoshis, S; Mazariegos, G; Abu-Elmagd, K; Bueno, J; Di, L

    1999-01-01

    BACKGROUND—Children with chronic intestinal pseudo-obstruction (CIPO) often require total parenteral nutrition (TPN) which puts them at risk of liver failure and recurrent line infections. Intestinal transplantation has become a therapeutic option for TPN dependent children with intestinal failure who are failing management with TPN.
AIMS—To investigate the outcome of children with CIPO referred for intestinal transplantation.
METHODS—A retrospective review was carried out of records and diagnostic studies from 27 patients with CIPO referred for intestinal transplantation.
RESULTS—Five children were not listed for transplantation: two because of parental decision, two because of suspicion of Munchausen syndrome by proxy, and one because he tolerated enteral nutrition. Six are still TPN dependent and awaiting transplantation. Eight children died awaiting transplantation. Eight children underwent transplantation. Three died (two months, seven months, and four years after transplant). Five children are alive with a median follow up of 2.6 years (range two months to six years). All transplanted children were able to tolerate full enteral feedings. The postoperative course was complicated by dumping syndrome, Munchausen syndrome by proxy, narcotic withdrawal, and uncovering of achalasia. Conclusion—Intestinal transplantation may be a life saving procedure in children with CIPO. Early referral and thorough pretransplant evaluation are keys to successful transplantation.


Keywords: intestinal transplantation; small bowel transplantation; children; chronic intestinal pseudo-obstruction; small bowel motility; total parenteral nutrition PMID:10486367

  16. Synthetic Small Intestinal Scaffolds for Improved Studies of Intestinal Differentiation

    PubMed Central

    Costello, Cait M.; Hongpeng, Jia; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David

    2014-01-01

    In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models. PMID:24390638

  17. Small intestinal bacterial overgrowth.

    PubMed

    Johnston, K L

    1999-03-01

    It is clear that the exact definition of small intestinal bacterial overgrowth (SIBO) needs to be reappraised in veterinary medicine. Antibiotic responsive enteropathies due to SIBO must be distinguished from those that are not associated with SIBO, such as those caused by a lack of immune tolerance. Once appropriate definitions and criteria for diagnosis are in place, the wide variety of diagnostic procedures that may facilitate the diagnosis can be evaluated with respect to their sensitivity and specificity, and statements about the prevalence and significance of this disorder can be made.

  18. [Intestinal hemorrhage due to multiple phlebectasias of the small intestine].

    PubMed

    Hammentgen, R; Kober, R; Beckmann, W; Lützeler, J

    1987-03-13

    A 37-year-old man had recurrent intestinal bleeding and resulting chronic anemia from multiple phlebectasias of the small intestine. Contrast medium studies and endoscopy of the intestine were negative. Abdominal angiography, however, demonstrated phlebectasias in the region supplied by the jejunal arteries. At operation and on examination of a resected portion of the jejunum, these multiple phlebectasias were demonstrated. Resection of the worst affected portion of the jejunum with end-to-end anastomosis was without complications postoperatively, the benzidine test on faeces was negative, and the blood-hemoglobin level gradually rose. Since radiological examination with contrast media and endoscopy are often negative in bleedings from vascular malformations of the intestine, abdominal angiography should be performed in case of intestinal bleedings not diagnosed by other methods.

  19. Monomeric C-reactive protein--a key molecule driving development of Alzheimer's disease associated with brain ischaemia?

    PubMed

    Slevin, M; Matou, S; Zeinolabediny, Y; Corpas, R; Weston, R; Liu, D; Boras, E; Di Napoli, M; Petcu, E; Sarroca, S; Popa-Wagner, A; Love, S; Font, M A; Potempa, L A; Al-Baradie, R; Sanfeliu, C; Revilla, S; Badimon, L; Krupinski, J

    2015-01-01

    Alzheimer's disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aβ, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244-372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aβ plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aβ/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia. PMID:26335098

  20. Piceatannol, a derivative of resveratrol, moderately slows INa inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts

    PubMed Central

    Chen, Wen-Pin; Hung, Li-Man; Hsueh, Chia-Hsiang; Lai, Ling-Ping; Su, Ming-Jai

    2009-01-01

    Background and purpose: Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts. Experimental approach: Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts. Key results: In rat ventricular cells, piceatannol (3–30 µmol·L−1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (Vmax) without altering Ca2+ transients. Piceatannol decreased peak INa and slowed INa inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 µmol·L−1) decreased peak INa without slowing INa inactivation. The inhibition of peak INa or Vmax was associated with a negative shift of the voltage-dependent steady-state INa inactivation curve without altering the activation threshold. At the concentrations more than 30 µmol·L−1, piceatannol could inhibit ICa,L, Ito, IKr, Ca2+ transients and Na+-Ca2+ exchange except IK1. Piceatannol (1–10 µmol·L−1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury. Conclusions and implications: The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in INa inhibition and uniquely slowing INa inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 µmol·L−1. PMID:19371352

  1. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    NASA Astrophysics Data System (ADS)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  2. Ischaemia-related cell damage in extracorporeal preserved tissue – new findings with a novel perfusion model

    PubMed Central

    Taeger, Christian D; Müller-Seubert, Wibke; Horch, Raymund E; Präbst, Konstantin; Münch, Frank; Geppert, Carol I; Birkholz, Torsten; Dragu, Adrian

    2014-01-01

    Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia-related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)-1-α as marker for hypoxia and of the pro-apoptotic protein Caspase-3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty-four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase-3 and HIF-1-α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase-3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF-1-α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase-3 and HIF-1-α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air. PMID:24636195

  3. Monomeric C-reactive protein-a key molecule driving development of Alzheimer’s disease associated with brain ischaemia?

    PubMed Central

    Slevin, M.; Matou, S.; Zeinolabediny, Y.; Corpas, R.; Weston, R.; Liu, D.; Boras, E.; Di Napoli, M.; Petcu, E.; Sarroca, S.; Popa-Wagner, A.; Love, S.; Font, M. A.; Potempa, L. A.; Al-baradie, R.; Sanfeliu, C.; Revilla, S.; Badimon, L.; Krupinski, J.

    2015-01-01

    Alzheimer’s disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aβ, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244–372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aβ plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aβ/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia. PMID:26335098

  4. Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery.

    PubMed

    Rogers, M L; Brennan, P A; Leong, C L; Gowers, S A N; Aldridge, T; Mellor, T K; Boutelle, M G

    2013-04-01

    We describe an enzyme-based electroanalysis system for real-time analysis of a clinical microdialysis sampling stream during surgery. Free flap tissue transfer is used widely in reconstructive surgery after resection of tumours or in other situations such as following major trauma. However, there is a risk of flap failure, due to thrombosis in the flap pedicle, leading to tissue ischaemia. Conventional clinical assessment is particularly difficult in such 'buried' flaps where access to the tissue is limited. Rapid sampling microdialysis (rsMD) is an enzyme-based electrochemical detection method, which is particularly suited to monitoring metabolism. This online flow injection system analyses a dialysate flow stream from an implanted microdialysis probe every 30 s for levels of glucose and lactate. Here, we report its first use in the monitoring of free flap reconstructive surgery, from flap detachment to re-vascularisation and overnight in the intensive care unit. The on-set of ischaemia by both arterial clamping and failure of venous drainage was seen as an increase in lactate and decrease in glucose levels. Glucose levels returned to normal within 10 min of successful arterial anastomosis, whilst lactate took longer to clear. The use of the lactate/glucose ratio provides a clear predictor of ischaemia on-set and subsequent recovery, as it is insensitive to changes in blood flow such as those caused by topical vasodilators, like papaverine. The use of storage tubing to preserve the time course of dialysate, when technical difficulties arise, until offline analysis can occur, is also shown. The potential use of rsMD in free flap surgery and tissue monitoring is highly promising.

  5. Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart.

    PubMed

    Wang, Ningyuan; Minatoguchi, Shinya; Chen, Xuehai; Uno, Yoshihiro; Arai, Masazumi; Lu, ChuanJiang; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi

    2004-07-01

    1 We examined whether antidiabetic drug miglitol could reduce ischaemia/reperfusion-induced myocardial apoptosis by attenuating production. 2 Japanese white rabbits were subjected to 30-min coronary occlusion followed by 4-h reperfusion with miglitol (10 mg kg(-1), i.v., n=20) or saline (n=20). The infarct area was determined by myoglobin staining, and the infarct size (IS) was expressed as a percentage of the area at risk. DNA fragmentation was assessed by TUNEL method and DNA ladder formation. The expression of Bcl-XL and Bax was detected by immunohistochemical analysis and Western blot analysis. Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, were measured during 30-min ischaemia and 30-min reperfusion in the absence (n=10) or presence of miglitol (10 mg kg(-1), i.v., n=10) using a microdialysis technique. 3 The IS was significantly reduced in the miglitol group (22.4+/-3.4%, n=10) compared to the control group (52.8+/-3.5%, n=10). Miglitol significantly decreased the 2,5-DHBA level during ischaemia and reperfusion and suppressed the incidence of TUNEL-positive myocytes in the ischaemic region (from 10.7+/-3.4 to 4.1+/-3.0%) and the intensity of DNA ladder formation. Miglitol significantly decreased the incidence of Bax-positive myocytes in the ischaemic region (7.4+/-1.7 vs 13.7+/-1.9% of the control) and significantly attenuated the upregulation of Bax protein in the ischaemic regions (from 179+/-17 to 90+/-12% of sham). There was no difference in the expression of Bcl-XL between the two groups. 4 These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein.

  6. A Case of Myeloid Sarcoma of Intestine.

    PubMed

    Lim, Sung Won; Lee, Hang Lak; Lee, Kang Nyeong; Jun, Dae Won; Kim, In Young; Kim, Eunjin; Ahn, Hyein; Park, Chan Kum

    2016-09-25

    Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year. Several studies recommend the same regimens of chemotherapy as used for circulating AML to treat isolated MS. We focused on the diagnosis of MS in this study. The correct diagnosis of MS is important for adequate treatment. In conclusion, MS should be considered in the differential diagnosis of intestinal tumor. PMID:27646584

  7. Intestinal microbiota and obesity.

    PubMed

    Blaut, Michael; Klaus, Susanne

    2012-01-01

    The human gut harbors a highly diverse microbial ecosystem of approximately 400 different species, which is characterized by a high interindividual variability. The intestinal microbiota has recently been suggested to contribute to the development of obesity and the metabolic syndrome. Transplantation of gut microbiota from obese mice to nonobese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient. Proposed mechanisms for the role of gut microbiota include the provision of additional energy by the conversion of dietary fiber to short-chain fatty acids, effects on gut-hormone production, and increased intestinal permeability causing elevated systemic levels of lipopolysaccharides (LPS). This metabolic endotoxemia is suggested to contribute to low-grade inflammation, a characteristic trait of obesity and the metabolic syndrome. Finally, activation of the endocannabinoid system by LPS and/or high-fat diets is discussed as another causal factor. In conclusion, there is ample evidence for a role of gut microbiota in the development of obesity in rodents. However, the magnitude of its contribution to human obesity is still unknown.

  8. [INTESTINAL TRANSPLANTATION IN PEDIATRICS

    PubMed

    Alarcón M, Pedro; Alarcón M, Jorge

    1997-01-01

    Intestinal Transplantation used to be an utopia in Medicine, and this was mainly due to the factor that the surgical technique was not the best at the beginning. When this was perfectioned, the next obstacle for the adequate progress of this surgery was the limited availability of anti-rejection drugs due to the fact that Ciclosporine has been and still is a drug of relative effectiveness. With the discovery of new anti-rejection drugs and with a best knowledge of the concomitant liver transplantation roll on the prognosis of these patients, it was possible to get in this decade, specifically in the last 2 years, extraordinary results; for example, from 170 pacients who underwent intestinal transplantation around the world, more than half were done by the University of Pittsburg. This university reported a survival of 62%. But, this percentage has been improved even more, the University of Miami reported a survival of 70% through the use of corticoides and two powerful anti-rejection drugs: FK-506 and Mycophelate.

  9. 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.

  10. 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.

  11. Campylobacter concisus – A New Player in Intestinal Disease

    PubMed Central

    Kaakoush, Nadeem Omar; Mitchell, Hazel Marjory

    2012-01-01

    Over the last decade Campylobacter concisus, a highly fastidious member of the Campylobacter genus has been described as an emergent pathogen of the human intestinal tract. Historically, C. concisus was associated with the human oral cavity and has been linked with periodontal lesions, including gingivitis and periodontitis, although currently its role as an oral pathogen remains contentious. Evidence to support the role of C. concisus in acute intestinal disease has come from studies that have detected or isolated C. concisus as sole pathogen in fecal samples from diarrheic patients. C. concisus has also been associated with chronic intestinal disease, its prevalence being significantly higher in children with newly diagnosed Crohn’s disease (CD) and adults with ulcerative colitis than in controls. Further C. concisus has been isolated from biopsy specimens of patients with CD. While such studies support the role of C. concisus as an intestinal pathogen, its isolation from healthy individuals, and failure of some studies to show a significant difference in C. concisus prevalence in subjects with diarrhea and healthy controls has raised contention as to its role in intestinal disease. Such findings could argue against the role of C. concisus in intestinal disease, however, the fact that C. concisus strains are genetically diverse raises the possibility that differences exist in their pathogenic potential. Evidence to support this view comes from studies showing strain specific differences in the ability of C. concisus to attach to and invade cells and produce virulence factors, including toxins and hemolytic phospholipase A. Further, sequencing of the genome of a C. concisus strain isolated from a child with CD (UNSWCD) and comparison of this with the only other fully sequenced strain (BAA-1457) would suggest that major differences exist in the genetic make-up of this species which could explain different outcomes of C. concisus infection. PMID:22919596

  12. [Malaria and intestinal protozoa].

    PubMed

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. PMID:26832999

  13. [Malaria and intestinal protozoa].

    PubMed

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately.

  14. Acute Diarrhea in Children.

    PubMed

    Radlović, Nedeljko; Leković, Zoran; Vuletić, Biljana; Radlović, Vladimir; Simić, Dušica

    2015-01-01

    Acute diarrhea (AD) is the most frequent gastroenterological disorder, and the main cause of dehydration in childhood. It is manifested by a sudden occurrence of three or more watery or loose stools per day lasting for seven to 10 days, 14 days at most. It mainly occurs in children until five years of age and particularly in neonates in the second half-year and children until the age of three years. Its primary causes are gastrointestinal infections, viral and bacterial, and more rarely alimentary intoxications and other factors. As dehydration and negative nutritive balance are the main complications of AD, it is clear that the compensation of lost body fluids and adequate diet form the basis of the child's treatment. Other therapeutic measures, except antipyretics in high febrility, antiparasitic drugs for intestinal lambliasis, anti-amebiasis and probiotics are rarely necessary. This primarily regards uncritical use of antibiotics and intestinal antiseptics in the therapy of bacterial diarrhea.The use of antiemetics, antidiarrhetics and spasmolytics is unnecessary and potentially risky, so that it is not recommended for children with AD. PMID:26946776

  15. Intestinal Folate Absorption

    PubMed Central

    Olinger, Edward J.; Bertino, Joseph R.; Binder, Henry J.

    1973-01-01

    These studies were designed to determine whether pteroylmonoglutamic acid (PGA) at physiologic concentrations is transported across the small intestine unaltered or is reduced and methylated to the circulating folate form (5-methyltetrahydrofolate [5-MeFH4]) during absorption. [3H]PGA was incubated in vitro on the mucosal side of rat jejunum. Of the folate transferred to the serosal side, the percent identified as 5-MeFH4 by DEAE-Sephadex chromtography was inversely related to the initial mucosa PGA concentration: at 7, 20, and 2,000 nM, 44%, 34%, and 2%, respectively, was converted to 5-MeFH4. In contrast, less than 4% of the folate transferred across ileal mucosa was 5-MeFH4 when the initial mucosa concentration was 20 nM. Specific activity of dihydrofolate (DHF) reductase, the enzyme responsible for converting PGA to tetrahydrofolic acid, was measured in villus homogenates and was significantly greater in the jejunum than in the ileum. 1,000 nM methotrexate (MTX), a DHF reductase inhibitor, markedly inhibited PGA conversion to 5-MeFH4 by the jejunum. Studies of transmural flux, initial rate of mucosal entry (influx) and mucosal accumulation (uptake) of folate were also performed. Although MTX did not alter the influx of PGA, MTX decreased jejunal mucosal uptake but increased transmural movement. Transmural folate movement across ileal mucosa was greater than across jejunal mucosa although mucosal uptake was greater in the jejunum than in the ileum. These results could explain previous studies which have failed to identify conversion of PGA to 5-MeFH4 when intestinal preparations have been exposed to higher and less physiologic concentrations of PGA. Further, these studies suggest that 5-MeFH4 may be retained by the jejunal mucosa. PMID:4727453

  16. [Results of comprehensive management of patients with chronic lower limb ischaemia using gene-engineering technologies of angiogenesis stimulation (Part 2)].

    PubMed

    Gavrilenko, A V; Voronov, D A

    2015-01-01

    Presented herein are the results of clinical use of gene engineering methods of stimulating angiogenesis in patients with lower limb chronic ischaemia. An open prospective controlled clinical study included a total of 160 patients with lower limb chronic ischaemia. Gene engineering technologies of angiogenesis stimulation were used both as an independent method of treatment in comprehensive conservative therapy (80 patients) and as comprehensive treatment in combination with revascularizing operations (80 patients). Part Two of the article deals with the results of using the above technologies in the composition of comprehensive treatment. It was shown that gene-engineering technologies of angiogenesis stimulation may successfully be used in comprehensive conservative treatment in patients with stage IIB CLLI, as well as stage III. Clinically meaningful improvement is confirmed by objective factors, including better parameters of regional haemodynamics, perfusion, functional reserve of blood flow, etc. Gene-engineering methods of angiogenesis stimulation were found demonstrated were associated with good tolerance and an admissible rate of adverse events in patients with CLLI. All undesirable events turned out transitory during the immediate follow-up period.

  17. Antioxidant/restorative effects of calcined gold preparations used in Indian systems of medicine against global and focal models of ischaemia.

    PubMed

    Shah, Zahoor Ahmad; Vohora, Shashi Bharat

    2002-05-01

    Stroke, or ischaemic brain damage, is of great geriatric importance being the third most common cause of death after cancer and heart diseases in developed countries. Despite such high frequency, its management has received inadequate attention. Many studies have shown the role of free radicals in the pathogenesis of ischaemic brain damage. Search for safe and effective antioxidant and free radial scavenger agents, therefore, appear to be a promising approach for stroke therapy. Gold, widely used in modern medicine for the treatment of rheumatoid arthritis, is highly valued for various medicinal uses in Indian systems of medicine. Traditional gold preparations are attributed with tonic/rejuvenating and antioxidant properties. Our earlier studies revealed interesting analgesic, immunostimulant, adaptogenic and glycogen sparing properties in these preparations, but their effects in cerebral ischaemia have not been investigated. This prompted us to initiate the present study using global and focal models of ischaemia in albino rats. Enzymatic parameters (lipid peroxidase, reduced glutathione, catalase, glutathione reductase, glutathione-S-transferase, glutatione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase) were employed to assess ischaemic brain damage and its modulation. Significant restoration of altered values to near normal levels by Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan (25 mg/kg, orally for 10 days), suggest potentials for gold preparations in cerebrovascular diseases. The preparations deserve more scientific attention for possible therapeutic exploitation.

  18. Intestinal protozoan infections in Malaysia.

    PubMed

    Lai, K P

    1992-12-01

    Intestinal protozoa are found in all communities in Malaysia and among all ethnic groups. Prevalence of intestinal protozoa is not affected by ethnicity but by living conditions. Communities with both basic amenities of safe water supply and proper toilets have lower prevalence than those with one or none of the amenity. Cryptosporidium is an important intestinal protozoon in Malaysia and should be included in future field and laboratory studies and also in laboratory diagnosis for pathogens. Much interest will be centered on Blastocystis hominis in future studies in view that it may be a cause of diarrhea. PMID:1298065

  19. Intestinal protozoan infections in Malaysia.

    PubMed

    Lai, K P

    1992-12-01

    Intestinal protozoa are found in all communities in Malaysia and among all ethnic groups. Prevalence of intestinal protozoa is not affected by ethnicity but by living conditions. Communities with both basic amenities of safe water supply and proper toilets have lower prevalence than those with one or none of the amenity. Cryptosporidium is an important intestinal protozoon in Malaysia and should be included in future field and laboratory studies and also in laboratory diagnosis for pathogens. Much interest will be centered on Blastocystis hominis in future studies in view that it may be a cause of diarrhea.

  20. Amebiasis and "nonpathogenic" intestinal protozoa.

    PubMed

    Aucott, J N; Ravdin, J I

    1993-09-01

    Infection with single or multiple species of intestinal protozoa is common in humans and can result in either asymptomatic colonization or symptoms of intestinal disease. Entamoeba histolytica serves as a paradigm for invasive colonic protozoal infection. The key to diagnosis and treatment of amebiasis is knowledge of the epidemiologic risk factors and clinical manifestations, a rational approach to diagnosis, and an understanding of the sites of action and uses of anti-amebic drugs. This knowledge of treatment provides a context for consideration of intestinal infection with less common protozoan pathogens such as Dientamoeba fragilis and Balantidium coli and 'nonpathogenic' protozoa such as Blastocystis hominis and Entamoeba coli. PMID:8254155

  1. Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction.

    PubMed

    Zhou, Mi; Bao, Yuqian; Li, Haobo; Pan, Yong; Shu, Lingling; Xia, Zhengyuan; Wu, Donghai; Lam, Karen S L; Vanhoutte, Paul M; Xu, Aimin; Jia, Weiping; Hoo, Ruby L-C

    2015-10-01

    Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.

  2. Magnetic resonance markers of ischaemia: their correlation with vasodilatory reserve in patients with carotid artery stenosis and occlusion

    PubMed Central

    Lythgoe, D; Simmons, A; Pereira, A; Cullinane, M; Williams, S; Markus, H

    2001-01-01

    OBJECTIVES—Better methods of identifying patients with asymptomatic carotid artery stenosis who are at high risk of stroke are required. It has been suggested that proton magnetic resonance spectroscopy (MRS) may allow the identification of ongoing ischaemia in this patient group by the detection of a potentially reversible reduction of N-acetyl aspartate (NAA), a presumed marker of neuronal integrity, and the presence of lactate, a marker of anaerobic metabolism. Previous studies have reported metabolite ratios rather than absolute concentrations. This study was performed to determine if NAA was reduced ipsilateral to carotid stenosis or occlusion, and if its concentration was related to carbon dioxide reactivity, a marker of cerebrovascular reserve.
METHODS— Twenty one patients with unilateral carotid stenosis (>70%) or occlusion were studied. Single voxel proton MRS was performed in the ipsilateral and contralateral hemispheres, with the voxel positioned in the arterial borderzone region between the middle and anterior cerebral artery territories. Absolute quantification of metabolite concentrations was performed. Cerebrovascular reactivity to 6% carbon dioxide was determined in both middle cerebral artery territories using transcranial Doppler ultrasonography.
RESULTS—Mean (SD) cerebrovascular reactivity was significantly lower in the stenosed compared with the contralateral hemisphere (13.3(7.7) v 19.2 (8.2)%/kPa, p=0.002). There were no significant differences in the absolute concentrations of NAA, choline, or creatine between the ipsilateral and contralateral hemispheres (for example, NAA 10.1 (1.1) v 10.5 (1.1) mmol/l, p=0.1). No lactate peak was seen in any spectra. For each metabolite measured, there was no correlation between the absolute concentration and cerebrovascular reactivity for either hemisphere.
CONCLUSIONS—In patients with carotid stenosis and occlusion we found no evidence that chronic hypoperfusion is associated with a

  3. [Remote results of treatment of patients with chronic lower-limb ischaemia by means of indirect revascularization and gene therapy].

    PubMed

    Chervyakov, Yu V; Staroverov, I N; Vlasenko, O N; Nersesyan, E G; Isaev, A A; Deev, R V

    2016-01-01

    Presented herein are comparative remote results of combined surgical treatment of 121 patients with stage IIB-III lower limb chronic ischaemia (LLCI) by means of indirect revascularization (lumbar sympathectomy--LSE and revascularizing osteotrepanation of the tibial bone--ROT) and gene therapy using the first registered Russian gene therapeutic agent Neovasculgen®. Depending on the LLCI degree and the method of treatment, during 3 years we assessed such parameters as the limb salvage rate, pain-free walk distance (PFWD), ankle-brachial index (ABI) and linear blood velocity (LBV). An increase in the PFWD in patients with initial stage IIB LLCI in the group of gene therapy was considerably higher than in other types of treatment (p=0.0001-0.0004). Using indirect methods of revascularization was accompanied and followed by less positive alterations in the PFWD values which by the end of the third year of follow up were observed to decrease. The values of PFWD after ROT at 2 and 3 years were higher than after LSE (p=0.006). During the first year of follow up the highest increment of the ABI was observed after ROT. At two years, the ABI values after ROT and gene therapy became equal. The worst result during 3 years as compared with other methods of treatment was demonstrated by LSE (p=0.006). Changes in ABI after gene therapy were statistically significant at all terms of follow up (p=0.008-0.02). There were no limb amputations in the remote period of follow up in patients with the initial stage IIB of the disease. Patients with initial stage III LLCI also showed a considerably better result by the increment of increased PFWD after gene-therapeutic treatment (p=0.001-0.0005). A small increment of the PFWD after LSE maintained during 1 year and after LSE during 2 years. The ABI values in all periods of follow up were higher after gene therapy (p=0.01-0.003). During the 2- and 3-year period the increment of this parameter after ROT was more significant than after LSE (p

  4. 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

  5. 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

    2016-01-01

    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

  6. Natural course of acute pancreatitis.

    PubMed

    Beger, H G; Rau, B; Mayer, J; Pralle, U

    1997-02-01

    Acute pancreatitis comprises, in terms of clinical, pathologic, biochemical, and bacteriologic data, four entities. Interstitial edematous pancreatitis and necrotizing pancreatitis are the most frequent clinical manifestations; pancreatic pseudocyst and pancreatic abscess are late complications after necrotizing pancreatitis, developing after 3 to 5 weeks. Determinants of the natural course of acute pancreatitis are pancreatic parenchymal necrosis, extrapancreatic retroperitoneal fatty tissue necrosis, biologically active compounds in pancreatic ascites, and infection of necrosis. Early in the course of acute pancreatitis multiple organ failure is the consequence of various inflammatory mediators that are released from the inflammatory process and from activated leukocytes attracted by pancreatic injury. During the late course, starting the second week, local and systemic septic complications are dominant. Around 80% of deaths in acute pancreatitis are caused by septic complications. The infection of pancreatic necrosis occurs in 8% to 12% of acute pancreatitis and in 30% to 40% of patients with necrotizing pancreatitis. Bacteriologic analysis of intraoperative smears and aspirates reveals predominantly gram-negative germs deriving from the intestine, most frequently Escherichia coli. It has been confirmed that after necrotizing pancreatitis a considerable large group of patients suffer long-lasting exocrine and endocrine insufficiency.

  7. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  8. 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

  9. Intestinal Failure (Short Bowel Syndrome)

    MedlinePlus

    ... while increasing enteral nutrition. Pre-digested and hypoallergenic formulas improve intestinal absorption, and extra vitamins and minerals are often added. These formulas are usually given slowly by a feeding tube ...

  10. Intestinal microbiota in liver disease.

    PubMed

    Haque, Tanvir R; Barritt, A Sidney

    2016-02-01

    The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.

  11. Chronic intestinal pseudo-obstruction

    PubMed Central

    Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna F; Caputo, Carla; Giorgio, Roberto De; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2008-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases. PMID:18494042

  12. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  13. Small intestinal bacterial overgrowth syndrome

    PubMed Central

    Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

    2010-01-01

    Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

  14. [Effect of hyperbaric oxygenation on local tissue blood flow to a small intestine transplant intended for esophagoplasty].

    PubMed

    Vinnitskiĭ, L I; Piuskiulian, L I; Zhidkov, I L; Demurov, E A

    1981-04-01

    The time course of the local tissue blood flow in the small intestinal graft used for esophagoplasty was studied in 54 acute experiments on rabbits exposed to hyperbaric oxygenation (1 hour, 2 ata). It has been shown that hyperbaric oxygenation prevents alterations in the local tissue blood flow in the small intestine. This fact provides evidence in favour of hyperbaric oxygenation application under clinical conditions.

  15. Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

    PubMed Central

    In, Julie G.; Foulke-Abel, Jennifer; Estes, Mary K.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark

    2016-01-01

    The development of indefinitely propagating human ‘mini-guts’ has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt–villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host pathogen interactions. PMID:27677718

  16. Effect of Deoxynivalenol and Other Type B Trichothecenes on the Intestine: A Review

    PubMed Central

    Pinton, Philippe; Oswald, Isabelle P.

    2014-01-01

    The natural food contaminants, mycotoxins, are regarded as an important risk factor for human and animal health, as up to 25% of the world’s crop production may be contaminated. The Fusarium genus produces large quantities of fusariotoxins, among which the trichothecenes are considered as a ubiquitous problem worldwide. The gastrointestinal tract is the first physiological barrier against food contaminants, as well as the first target for these toxicants. An increasing number of studies suggest that intestinal epithelial cells are targets for deoxynivalenol (DON) and other Type B trichothecenes (TCTB). In humans, various adverse digestive symptoms are observed on acute exposure, and in animals, these toxins induce pathological lesions, including necrosis of the intestinal epithelium. They affect the integrity of the intestinal epithelium through alterations in cell morphology and differentiation and in the barrier function. Moreover, DON and TCTB modulate the activity of intestinal epithelium in its role in immune responsiveness. TCTB affect cytokine production by intestinal or immune cells and are supposed to interfere with the cross-talk between epithelial cells and other intestinal immune cells. This review summarizes our current knowledge of the effects of DON and other TCTB on the intestine. PMID:24859243

  17. [The pneumodynamic barium x-ray study of small intestine adhesions (a preliminary report)].

    PubMed

    Baev, S; Nikolov, P

    1990-01-01

    Small-intestinal adhesions are not very rare, but on conventional X-ray examination are frequently missed because of their poor semiotics. By the method of pneumodynamic-barium X-ray examination, which allows to obtain high-quality double-contrast image, in addition to the better visualized classical symptoms--exostotic rebounds, diverticulum-like deformities, peristaltic spasms, spastic contractions etc, one may evince also the following new criteria: when inflated the intestines do not freely increase their volume, as is normal, are not unplaited along the entire abdomen, but remain amassed in a definite zone (usually in the left half); On external pressure the inflated loops do not move, as do the ones without adhesions, but remain fixed, so that their structure remains unchanged. The intestinal loops are crooked with acute angles; when in a normally inflated state, they are not crooked, but long. A frequent finding in small intestinal adhesions are the V-shaped figures in whose bottom there is barium meal over which air passes. A study of the small-intestinal cannon contraction reveals insufficiency in the hydrodynamics of the intestinal passage, marked by delayed evacuation, in spite of the strong peristalsis. This method allows a more precise elucidation than the conventional X-ray examination of the abdominal status in small-intestinal adhesions and better orientates the surgeon to choose conservative or operative treatment.

  18. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy

    PubMed Central

    Park, Sang Won; Chen, Sean W.C.; Kim, Mihwa; Brown, Kevin M.; Kolls, Jay K.; D’Agati, Vivette D.; Lee, H. Thomas

    2010-01-01

    Patients with acute kidney injury (AKI) frequently suffer from extra-renal complications including hepatic dysfunction and systemic inflammation. We aimed to determine the mechanisms of AKI induced hepatic dysfunction and systemic inflammation. Mice subjected to AKI [renal ischemia reperfusion (IR) or nephrectomy] rapidly developed acute hepatic dysfunction and suffered significantly worse hepatic IR injury. After AKI, rapid peri-portal hepatocyte necrosis, vacuolization, neutrophil infiltration and pro-inflammatory mRNA upregulation were observed suggesting an intestinal source of hepatic injury. Small intestine histology after AKI demonstrated profound villous lacteal capillary endothelial apoptosis, disruption of vascular permeability and epithelial necrosis. After ischemic or non-ischemic AKI, plasma TNF-α, IL-17A and IL-6 increased significantly. Small intestine appears to be the source of IL-17A as IL-17A levels were higher in the portal circulation and small intestine compared to the levels measured from the systemic circulation and liver. Wild type mice treated with neutralizing antibodies against TNF-α, IL-17A or IL-6 or mice deficient in TNF-α, IL-17A, IL-17A receptor or IL-6 were protected against hepatic and small intestine injury due to ischemic or non-ischemic AKI. For the first time, we implicate the increased release of IL-17A from small intestine together with induction of TNF-α and IL-6 as a cause of small intestine and liver injury after ischemic or non-ischemic AKI. Modulation of the inflammatory response and cytokine release in the small intestine after AKI may have important therapeutic implications in reducing complications arising from AKI. PMID:20697374

  19. The equine intestinal microbiome.

    PubMed

    Costa, Marcio C; Weese, J Scott

    2012-06-01

    The equine intestinal tract contains a complex microbial population (microbiota) that plays an important role in health and disease. Despite the undeniable importance of a 'normal' microbiota, understanding of the composition and function of this population is currently limited. As methods to characterize the microbiota and its genetic makeup (the microbiome) have evolved, the composition and complexity of this population are starting to be revealed. As is befitting a hindgut fermenter, members of the Firmicutes phylum appear to predominate, yet there are significant populations of numerous other phyla. The microbiome appears to be profoundly altered in certain disease states, and better understanding of these alterations may offer hope for novel preventive and therapeutic measures. The development and increasing availability of next generation sequencing and bioinformatics methods offer a revolution in microbiome evaluation and it is likely that significant advances will be made in the near future. Yet, proper use of these methods requires further study of basic aspects such as optimal testing protocols, the relationship of the fecal microbiome to more proximal locations where disease occurs, normal intra- and inter-horse variation, seasonal variation, and similar factors. PMID:22626511

  20. Complicated intestinal atresias.

    PubMed

    Miller, R C

    1979-05-01

    In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction.

  1. The ‘de novo’ DNA methyltransferase Dnmt3b compensates the Dnmt1-deficient intestinal epithelium

    PubMed Central

    Elliott, Ellen N; Sheaffer, Karyn L; Kaestner, Klaus H

    2016-01-01

    Dnmt1 is critical for immediate postnatal intestinal development, but is not required for the survival of the adult intestinal epithelium, the only rapidly dividing somatic tissue for which this has been shown. Acute Dnmt1 deletion elicits dramatic hypomethylation and genomic instability. Recovery of DNA methylation state and intestinal health is dependent on the de novo methyltransferase Dnmt3b. Ablation of both Dnmt1 and Dnmt3b in the intestinal epithelium is lethal, while deletion of either Dnmt1 or Dnmt3b has no effect on survival. These results demonstrate that Dnmt1 and Dnmt3b cooperate to maintain DNA methylation and genomic integrity in the intestinal epithelium. DOI: http://dx.doi.org/10.7554/eLife.12975.001 PMID:26808831

  2. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status.

    PubMed

    Tourret, Jérôme; Willing, Benjamin P; Croxen, Matthew A; Dufour, Nicolas; Dion, Sara; Wachtel, Sarah; Denamur, Erick; Finlay, B Brett

    2016-01-01

    Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity. PMID:27096607

  3. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status.

    PubMed

    Tourret, Jérôme; Willing, Benjamin P; Croxen, Matthew A; Dufour, Nicolas; Dion, Sara; Wachtel, Sarah; Denamur, Erick; Finlay, B Brett

    2016-01-01

    Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity.

  4. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status

    PubMed Central

    Willing, Benjamin P.; Croxen, Matthew A.; Dufour, Nicolas; Dion, Sara; Wachtel, Sarah; Denamur, Erick; Finlay, B. Brett

    2016-01-01

    Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity. PMID:27096607

  5. Acute gastroenteritis.

    PubMed

    Graves, Nancy S

    2013-09-01

    Acute gastroenteritis is a common infectious disease syndrome, causing a combination of nausea, vomiting, diarrhea, and abdominal pain. There are more than 350 million cases of acute gastroenteritis in the United States annually and 48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea affects more than half of people traveling from developed countries to developing countries. In adult and pediatric patients, the prevalence of Clostridium difficile is increasing. Contact precautions, public health education, and prudent use of antibiotics are necessary goals in decreasing the prevalence of Clostridium difficle. Preventing dehydration or providing appropriate rehydration is the primary supportive treatment of acute gastroenteritis.

  6. Effects of transient global ischaemia on freezing behaviour and activity in a context-dependent fear conditioning task--implications for memory investigations.

    PubMed

    Henrich-Noack, Petra; Krautwald, Karla; Reymann, Klaus G; Wetzel, Wolfram

    2011-07-15

    Transient global ischaemia induces cell death in the CA1 layer of the hippocampus. To evaluate the functional consequences, we performed context-dependent fear conditioning. Ischaemia was induced by 2-vessel-occlusion (2VO) in gerbils. On day 6 post ischaemia or sham procedures (in control group) gerbils were placed in a test chamber and after 3 min adaption time exposed to foot-shocks (training session). On the next day the animals were placed in the same test chamber without foot-shocks (test session). As a parameter for memory performance we used the standard method of measuring the total freezing time via a cumulative time-sampling procedure during the test session. We found a significant longer total freezing time in control animals than in ischaemic animals. In addition, however, we applied a more detailed analysis of (i) quantifying the number of freezing bouts, (ii) the average duration of single freezing bouts, (iii) the activity pattern during the training and test situation and (iv) we differentially evaluated all the single time segments of the experiment. These analyses revealed that although maintenance of freezing (duration of freezing bout) was significantly lower in ischaemic animals compared to controls, the initiation of freezing (number of freezing bouts) was not significantly different between the two groups during the test session. The activity scores of ischaemic and non-ischaemic gerbils were similar during the adaption time of the training session. The foot-shock, however, induced a significantly different pattern of behaviour in the ischaemic animals, which was selectively reproduced during the test session. In conclusion, ischaemic gerbils reacted to a fearsome thread with a behavioural pattern different from unlesioned animals and they revealed this specific foot-shock induced behaviour again during the test session. This indicated that CA1 hippocampal death did not interrupt memory performance but changed expression of fear. Therefore

  7. Interstitial and arterial–venous [K+] in human calf muscle during dynamic exercise: effect of ischaemia and relation to muscle pain

    PubMed Central

    Green, Simon; Langberg, Henning; Skovgaard, Dorthe; Bülow, Jens; Kjær, Michael

    2000-01-01

    Changes in the concentration of interstitial K+ surrounding skeletal muscle fibres ([K+]I) probably play some role in the regulation of cardiovascular adjustments to muscular activity, as well as in the aetiology of muscle pain and fatigue during high-intensity exercise. However, there is very little information on the response of [K+]I to exercise in human skeletal muscle. Five young healthy subjects performed plantar flexion exercise for four 5 min periods at increasing power outputs (∼1–6 W) with 10 min intervening recovery periods, as well as for two 5 min periods with ischaemia at ∼1 and ∼3 W. Microdialysis probes were inserted into the gastrocnemius medialis muscle of the right leg to measure [K+]I, and K+ release from the plantar flexors during and after incremental exercise was calculated from plasma flow and arterial–venous differences for K+. Calf muscle pain was assessed using a visual analogue scale. On average, [K+]I was 4.4 mmol l−1 at rest and increased during minutes 3–5 of incremental exercise by ∼1–7 mmol l−1 as a positive function of power output. K+ release also increased as a function of exercise intensity, although there was a progressive increase by ∼1–6 mmol l−1 in the [K+] gradient between the interstitium and arterial–venous plasma. [K+]I was lower during ischaemic exercise than control exercise. In contrast to this effect of ischaemia on [K+]I, muscle pain was relatively higher during ischaemic exercise, which demonstrates that factors other than changes in [K+]I are responsible for ischaemic muscle pain. In conclusion, this study has demonstrated that during 5 min of dynamic exercise, [K+]I increases during the later period of exercise as a positive function of exercise intensity, ischaemia reduces [K+]I during rest and exercise, and the increase in [K+]I is not responsible for muscle pain during ischaemic exercise. PMID:11118511

  8. Nicotine-induced exocytotic norepinephrine release in guinea-pig heart, human atrium and bovine adrenal chromaffin cells: modulation by single components of ischaemia.

    PubMed

    Krüger, C; Haunstetter, A; Gerber, S; Serf, C; Kaufmann, A; Kübler, W; Haass, M

    1995-08-01

    The influence of single components of myocardial ischaemia, such as anoxia, substrate withdrawal, hyperkalemia and extracellular acidosis, on nicotine-induced norepinephrine (NE) release was investigated in the isolated perfused guinea-pig heart, in incubated human atrial tissue and in cultured bovine adrenal chromaffin cells (BCC). In normoxia, nicotine (1-1000 mumol/l) evoked a concentration-dependent release of NE (determined by high pressure liquid chromatography and electrochemical detection) from guinea-pig heart and human atrium. In contrast to selective anoxia (Po2 < 5 mmHg) or glucose withdrawal, respectively, anoxia in combination with glucose withdrawal (5-40 min) markedly potentiated nicotine-induced NE release both in guinea-pig heart and human atrium. The sensitization of cardiac sympathetic nerve endings to nicotine was characterized by a lower threshold concentration and an approximate two-fold increase of maximum NE release, peaking after 10 min of anoxia and glucose withdrawal. Cyanide intoxication (1 mmol/l) combined with glucose withdrawal resulted in a similar increase of nicotine-induced sympathetic transmitter release both in guinea-pig heart and human atrium. In contrast, the nicotine-induced (10 mumol/l) NE overflow was only slightly potentiated by 10 min of global ischaemia in guinea-pig heart. Both hyperkalemia ([K+] 16 mmol/l) and acidosis (pH 6.8-6.0) distinctly attenuated the stimulatory effect of nicotine in guinea-pig heart and human atrium under normoxic conditions. Consistent with an exocytotic release mechanism, NE release was dependent on the presence of extracellular calcium under all conditions tested. Furthermore, NE overflow from guinea-pig heart was accompanied by a release of the exocytosis marker neuropeptide Y (NPY; determined by radioimmunoassay). In BCC, nicotine (1-10 mumol/l) evoked a release of NE and NPY and a transient rise of [Ca2+]i (determined with fura-2) during normoxia which were both dependent on the

  9. Effects of transient global ischaemia on freezing behaviour and activity in a context-dependent fear conditioning task--implications for memory investigations.

    PubMed

    Henrich-Noack, Petra; Krautwald, Karla; Reymann, Klaus G; Wetzel, Wolfram

    2011-07-15

    Transient global ischaemia induces cell death in the CA1 layer of the hippocampus. To evaluate the functional consequences, we performed context-dependent fear conditioning. Ischaemia was induced by 2-vessel-occlusion (2VO) in gerbils. On day 6 post ischaemia or sham procedures (in control group) gerbils were placed in a test chamber and after 3 min adaption time exposed to foot-shocks (training session). On the next day the animals were placed in the same test chamber without foot-shocks (test session). As a parameter for memory performance we used the standard method of measuring the total freezing time via a cumulative time-sampling procedure during the test session. We found a significant longer total freezing time in control animals than in ischaemic animals. In addition, however, we applied a more detailed analysis of (i) quantifying the number of freezing bouts, (ii) the average duration of single freezing bouts, (iii) the activity pattern during the training and test situation and (iv) we differentially evaluated all the single time segments of the experiment. These analyses revealed that although maintenance of freezing (duration of freezing bout) was significantly lower in ischaemic animals compared to controls, the initiation of freezing (number of freezing bouts) was not significantly different between the two groups during the test session. The activity scores of ischaemic and non-ischaemic gerbils were similar during the adaption time of the training session. The foot-shock, however, induced a significantly different pattern of behaviour in the ischaemic animals, which was selectively reproduced during the test session. In conclusion, ischaemic gerbils reacted to a fearsome thread with a behavioural pattern different from unlesioned animals and they revealed this specific foot-shock induced behaviour again during the test session. This indicated that CA1 hippocampal death did not interrupt memory performance but changed expression of fear. Therefore

  10. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison

    PubMed Central

    Chalela, Julio A; Kidwell, Chelsea S; Nentwich, Lauren M; Luby, Marie; Butman, John A; Demchuk, Andrew M; Hill, Michael D; Patronas, Nicholas; Latour, Lawrence; Warach, Steven

    2007-01-01

    Summary Background Although the use of magnetic resonance imaging (MRI) for the diagnosis of acute stroke is increasing, this method has not proved more effective than computed tomography (CT) in the emergency setting. We aimed to prospectively compare CT and MRI for emergency diagnosis of acute stroke. Methods We did a single-centre, prospective, blind comparison of non-contrast CT and MRI (with diffusion-weighted and susceptibility weighted images) in a consecutive series of patients referred for emergency assessment of suspected acute stroke. Scans were independently interpreted by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. Results 356 patients, 217 of whom had a final clinical diagnosis of acute stroke, were assessed. MRI detected acute stroke (ischaemic or haemorrhagic), acute ischaemic stroke, and chronic haemorrhage more frequently than did CT (p<0.0001, for all comparisons). MRI was similar to CT for the detection of acute intracranial haemorrhage. MRI detected acute ischaemic stroke in 164 of 356 patients (46%; 95% CI 41-51%), compared with CT in 35 of 356 patients (10%; 7-14%). In the subset of patients scanned within 3 h of symptom onset, MRI detected acute ischaemic stroke in 41 of 90 patients (46%; 35-56%); CT in 6 of 90 (7%; 3-14%). Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78-88%) and CT of 26% (56 of 217; 20-32%) for the diagnosis of any acute stroke. Interpretation MRI is better than CT for detection of acute ischaemia, and can detect acute and chronic haemorrhage; therefore it should be the preferred test for accurate diagnosis of patients with suspected acute stroke. Because our patient sample encompassed the range of disease that is likely to be encountered in emergency cases of suspected stroke, our results are directly applicable to clinical practice. PMID:17258669

  11. 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

  12. 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

  13. 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.

  14. Nutritional support in acute and chronic pancreatitis.

    PubMed

    Grant, John P

    2011-08-01

    Nutritional support can have a significant beneficial impact on the course of moderate to severe acute pancreatitis. Enteral nutrition is preferred, with emphasis on establishment of jejunal access; however, parenteral nutrition can also be of value if intestinal failure is present. Early initiation of nutritional support is critical, with benefits decreasing rapidly if begun after 48 hours from admission. Severe malnutrition in chronic pancreatitis can be avoided or treated with dietary modifications or enteral nutrition.

  15. Nifuroxazide in acute diarrhoea: OTC preparation. Irrational.

    PubMed

    1999-12-01

    (1) Nifuroxazide, an intestinal antibacterial agent, is now available in France, without a prescription, for the treatment of acute diarrhoea in adults. (2) According to the only available comparative randomised trial, there is no effect on dehydration. Relative to a placebo, the mean number of stools is reduced by about one per day during the first two days of treatment, with no significant difference thereafter. PMID:11503813

  16. Acute abdomen due to small bowel anisakiasis.

    PubMed

    Pellegrini, M; Occhini, R; Tordini, G; Vindigni, C; Russo, S; Marzocca, G

    2005-01-01

    The popularity in Western countries of dishes based on raw fish has led to an increased incidence of anisakiasis, a human parasitic disease caused by the ingestion of live anisakid larvae. The entire digestive tract may be involved, but the stomach and the small intestine are the most frequently affected sites. We report a case of acute abdomen due to Anisakis simplex infection that caused small bowel obstruction. PMID:15702863

  17. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  18. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  19. Intestinal failure: Pathophysiological elements and clinical diseases

    PubMed Central

    Ding, Lian-An; Li, Jie-Shou

    2004-01-01

    There are two main functions of gastrointestinal tract, digestion and absorption, and barrier function. The latter has an important defensive effect, which keeps the body away from the invading and damaging of bacteria and endotoxin. It maintains the systemic homeostasis. Intestinal dysfunction would happen when body suffers from diseases or harmful stimulations. The lesser dysfunction of GI tract manifests only disorder of digestion and absorption, whereas the more serious intestinal disorders would harm the intestinal protective mechanism, or intestinal barrier function, and bacterial/endotoxin translocation, of intestinal failure (IF) would ensue. This review disscussed the theory of the intestinal failure, aiming at attracting recognition and valuable comments by clinicians. PMID:15052668

  20. Primary intestinal lymphangiectasia (Waldmann's disease)

    PubMed Central

    Vignes, Stéphane; Bellanger, Jérôme

    2008-01-01

    Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective

  1. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  2. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  3. Human intestinal capillariasis in Thailand

    PubMed Central

    Saichua, Prasert; Nithikathkul, Choosak; Kaewpitoon, Natthawut

    2008-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Capillaria-prevalent area. Sisaket, in northeast Thailand, was the first province which has reported intestinal capillariasis. Moreover, Buri Ram presented a high prevalence of intestinal capillariasis, totaling 24 cases from 1994-2006. About half of all cases have consumed raw or undercooked fish. However, even if the numbers of the intestinal capillariasis cases in Thailand is reduced, C. philippinensis infection cases are still reported. The improvement of personal hygiene, specifically avoiding consumption of undercooked fish and promoting a health education campaign are required. These strategies may minimize or eliminate C. philippinensis infection in Thailand. PMID:18203280

  4. Acquired causes of intestinal malabsorption.

    PubMed

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  5. Confusing untypical intestinal Behcet’s disease: Skip ulcers with severe lower gastrointestinal hemorrhage

    PubMed Central

    Wang, Zhen-Kai; Shi, Hui; Wang, Shao-Dong; Liu, Jiong; Zhu, Wei-Ming; Yang, Miao-Fang; Liu, Chan; Lu, Heng; Wang, Fang-Yu

    2014-01-01

    Behcet’s disease (BD) is a rare and life-long disorder characterized by inflammation of blood vessels throughout the body. BD was originally described in 1937 as a syndrome involving oral and genital ulceration in addition to ocular inflammation. Intestinal BD refers to colonic ulcerative lesions documented by objective measures in patients with BD. Many studies have shown that over 40% of BD patients have gastrointestinal complaints. Symptoms include abdominal pain, diarrhea, nausea, anorexia and abdominal distension. Although gastrointestinal symptoms are common, the demonstration of gastrointestinal ulcers is rare. This so-called intestinal BD accounts for approximately 1% of cases. There is no specific test for BD, and the diagnosis is based on clinical criteria. The manifestations of intestinal BD are similar to those of other colitis conditions such as Crohn’s disease or intestinal tuberculosis, thus, it is challenging for gastroenterologists to accurately diagnose intestinal BD in patients with ileo-colonic ulcers. However, giant ulcers distributed in the esophagus and ileocecal junction with gastrointestinal hemorrhage are rare in intestinal BD. Here, we present a case of untypical intestinal BD. The patient had recurrent aphthous ulceration of the oral mucosa, and esophageal and ileo-colonic ulceration, but no typical extra-intestinal symptoms. During examination, the patient had massive acute lower gastrointestinal bleeding. The patient underwent ileostomy after an emergency right hemicolectomy and partial ileectomy, and was subsequently diagnosed with incomplete-type intestinal BD by pathology. The literature on the evaluation and management of this condition is reviewed. PMID:24527178

  6. Regulation of C/EBPdelta-dependent transactivation by histone deacetylases in intestinal epithelial cells.

    PubMed

    Turgeon, Naomie; Valiquette, Caroline; Blais, Mylène; Routhier, Sophie; Seidman, Ernest G; Asselin, Claude

    2008-04-01

    The C/EBPdelta transcription factor is involved in the positive regulation of the intestinal epithelial cell acute phase response. C/EBPdelta regulation by histone deacetylases (HDACs) during the course of inflammation remains to be determined. Our aim was to examine the effect of HDACs on C/EBPdelta-dependent regulation of haptoglobin, an acute phase protein induced in intestinal epithelial cells in response to pro-inflammatory cytokines. HDAC1, HDAC3, and HDAC4 were expressed in intestinal epithelial cells, as determined by Western blot. GST pull-do