Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia/reoxygenation (H/R)-induced intestinal injury plays a significant role in the development of necrotizing enterocolitis (NEC). We experimentally explored the effect of pentoxifylline (PTX) on an NEC model. Twenty-one newborn rabbits were divided into three groups: group 1 (control), group 2 (H/R) and group 3 (H/R + PTX). Five minutes of reoxygenation following 5 min of hypoxia was performed three times a day during 3 days. Before each H/R procedure in the H/R + PTX group, the rabbits were treated with PTX 25 mg/kg intraperitoneally. Animals were sacrificed on the third day and ileum samples were taken for histopathological examination and biochemical enzyme studies [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST)]. There was a significant difference in the grade and number of the intestinal lesions between controls and the H/R and H/R + PTX groups (p < 0.001), but no significant difference was found between the H/R and the H/R + PTX groups (p > 0.05). Intestinal SOD, GR and GST activities in the H/R and H/R + PTX groups were significantly higher than in the control group (p < 0.05); however, there was no significant difference between the H/R and H/R + PTX groups (p > 0.05). Significantly reduced GPx activity was found in the H/R and H/R + PTX groups compared with the controls (p < 0.05). No significant difference in GPx activity existed between the H/R group and the H/R + PTX group (p > 0.05). Ischemia/reperfusion injury was responsible for mediating hypoxia-induced intestinal necrosis in NEC and PTX pretreatment did not have a protective effect on NEC.
 ...
PMID:Pentoxifylline does not prevent hypoxia/reoxygenation-induced necrotizing enterocolitis. An experimental study. 1501 17

Necrotizing enterocolitis (NEC) is the most common surgical emergency in the neonatal intensive care unit and remains a major cause of death in neonates. Although the pathophysiology of NEC has not been completely elucidated, progress has been made in the characterization of the molecular events which may take place during an episode of ischemia. This possible initiating event is followed by a complex cascade of inflammatory mediators active in NEC: epidermal growth factor, platelet-activating factor, and, nitric oxide. Additionally, unique characteristics of the premature gut are thought to be crucial to the development of NEC. The diagnosis of NEC continues to be based on clinical and radiographic features. Several new laboratory tests are under investigation for the purposes of earlier diagnosis, but none have prevailed at this time. Both exploratory laparotomy, with intestinal resection and peritoneal drainage are widely practiced. Mortality rates remain high and have improved little over the last couple of decades. Therefore, prevention remains crucial in order to decrease the incidence of NEC. Cautious feeding regimens, the use of maternal breast milk, passive immunization, and the use of probiotics have all been suggested but not proven as possible preventive methods. Although many advances have been made, significant opportunity remains to improve our understanding of the disease process and to develop better strategies for prevention and treatment.
 ...
PMID:Current issues in the management of necrotizing enterocolitis. 1528 1

A full-term baby girl presented on the 14th day of life with an appendiceal abscess on a basis of appendicular perforation. Pathologic examination found focal transmural coagulation necrosis suggesting an ischemic origin for the perforation. It is argued that appendiceal perforation in the newborn period is a different disease entity than appendiceal perforation later in life. In the newborn, ischemia seems to be the leading pathogenetic factor, and neonatal appendiceal perforation seems, therefore, related to neonatal necrotizing enterocolitis.
 ...
PMID:Further evidence for an ischemic origin of perforation of the appendix in the neonatal period. 1530 May 57

Ischemia-reperfusion injury of the intestine is a significant problem in abdominal aortic aneurysm surgery, small bowel transplantation, cardiopulmonary bypass, strangulated hernias, and neonatal necrotizing enterocolitis. It can also occur as a consequence of collapse of systemic circulation, as in hypovolemic and septic shock. It is associated with a high morbidity and mortality. This article is a comprehensive review of the current status of the molecular biology and the strategies to prevent ischemia-reperfusion injury of the intestine. Various treatment modalities have successfully been applied to attenuate reperfusion injury in animal models of reperfusion injury of the intestine. Ischemic preconditioning has been found to be the most promising strategy against reperfusion injury during the last few years, appearing to increase the tolerance of the intestine to reperfusion injury. Although ischemic preconditioning has been shown to be beneficial in the human heart and the liver, prospective controlled studies in humans involving ischemic preconditioning of the intestine are lacking. Research focused on the application of novel drugs that can mimic the effects of ischemic preconditioning to manipulate the cellular events during reperfusion injury of the intestine is required.
 ...
PMID:Ischemia-reperfusion injury of the intestine and protective strategies against injury. 1548 5

Necrotizing enterocolitis continues to be a common and life-threatening gastrointestinal emergency in the low birth weight infant. Prematurity, ischemia, enteral feeding, and infectious disease have been identified as common risk factors, however the exact cause of NEC other than prematurity is yet to be identified. Good assessment skills by the nurse are imperative, because clinical signs of NEC can be both subtle and catastrophic. Frequent radiographs are essential for the diagnosis of NEC and ongoing assessment of neonates diagnosed with NEC. Radiographs including an abdominal flat plate examination and a left lateral decubitus film to evaluate for free air should be obtained every 6-8 hours in the neonates with Stages II and III NEC.
 ...
PMID:Pathophysiology and current management of necrotizing enterocolitis. 1571 34

While it is accepted that ischemia contributes to the pathogenesis of necrotizing enterocolitis (NEC), three important questions regarding this role subsist. First, where within the intestinal circulation does the vascular pathophysiology occur? It is most likely that this event begins within the intramural microcirculation, particularly the small arteries that pierce the gut wall and the submucosal arteriolar plexus insofar as these represent the principal sites of resistance regulation in the gut. Mucosal damage might also disrupt the integrity or function of downstream villous arterioles leading to damage thereto; thereafter, noxious stimuli might ascend into the submucosal vessels via downstream venules and lymphatics. Second, when during the course of pathogenesis does ischemia occur? Ischemia is unlikely to the sole initiating factor of NEC; instead, it is more likely that ischemia is triggered by other events, such as inflammation at the mucosal surface. In this context, it is likely that ischemia plays a secondary, albeit critical role in disease extension. Third, how does the ischemia occur? Regulation of vascular resistance within newborn intestine is principally determined by a balance between the endothelial production of the vasoconstrictor peptide endothelin-1 (ET-1) and endothelial production of the vasodilator free radical nitric oxide (NO). Under normal conditions, the balance heavily favors NO-induced vasodilation, leading to a low resting resistance and high rate of flow. However, factors that disrupt endothelial cell function, eg, ischemia-reperfusion, sustained low-flow perfusion, or proinflammatory mediators, alter the ET-1:NO balance in favor of constriction. The unique ET-1-NO interaction thereafter might facilitate rapid extension of this constriction, generating a viscous cascade wherein ischemia rapidly extends into larger portions of the intestine.
 ...
PMID:Ischemia and necrotizing enterocolitis: where, when, and how. 1608 2

Necrotizing enterocolitis (NEC) is a common, life-threatening neonatal gastrointestinal disease; it affects approximately 11% of extremely premature neonates. The etiology of NEC is multifactorial. Risk factors may roughly be grouped into four main categories: prematurity; transient ischemia of the intestine; local/systemic inflammation predisposing the bowel to injury, and therapeutic interventions. Recent studies have shown that carrier state of genetic polymorphisms may be associated with perinatal morbidity, including NEC. In perinatal disorders, the significance of genetic variants of cytokines, the renin-angiotensin-aldosterone system, and surfactant proteins have been investigated most widely. Positive findings indicate the implication of genetic polymorphisms of proinflammatory cytokines in premature birth; angiotensin converting enzyme in perinatal adaptation and angiotensin type 1 receptor in the closure of ductus arteriosus; surfactant proteins A and B in respiratory distress syndrome; interleukin (IL)-6 in sepsis, and IL-4-receptor alpha chain and IL-18 in NEC. This review provides an insight into the genetics of NEC and summarizes genetic data in light of pathologic processes leading to NEC.
 ...
PMID:Genetic basis for necrotizing enterocolitis--risk factors and their relations to genetic polymorphisms. 1614 53

Necrotizing enterocolitis (NEC) is a devastating inflammatory condition of the gut that occurs in premature infants. Ischemia-reperfusion gut injury with production of reactive oxygen species (ROS) is thought to contribute to NEC; the exact cellular mechanisms involved are largely unknown. The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress-induced intestinal epithelial cell apoptosis. H2O2 treatment resulted in rat intestinal epithelial cell apoptosis in a dose- and time-dependent manner; the caspase inhibitor, zVAD-fmk, blocked this response. Western blotting was performed to determine phosphorylation of kinases and ELISA was used to assess DNA fragmentation, as a measure of apoptosis. A rapid increase in phosphorylation of extracellular signal-related kinase (ERK)1/2, c-Jun N-terminal kinase (JNK)1/2, and Akt was noted. Inhibition of ERK and JNK decreased H2O2-induced apoptosis. Additionally, inhibition of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3-K) attenuated and enhanced H2O2-mediated apoptosis and mitochondrial membrane potential decrease, respectively. Furthermore, activation of PKC reduced the Akt phosphorylation, whereas inhibition of PKC attenuated H2O2-mediated activation of caspase-3 and enhanced the H2O2-induced Akt phosphorylation. This study shows that activation of multiple signaling transduction pathways occurs during oxidative stress-induced intestinal epithelial cell injury. In contrast to ERK, JNK, and PKC, PI3-K/Akt may play an important role as a protective cellular signaling pathway during this process.
 ...
PMID:Signal transduction pathways involved in oxidative stress-induced intestinal epithelial cell apoptosis. 1630 92

Heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, can protect intestinal epithelial cells from various forms of injury in vitro and attenuate intestinal ischemia/reperfusion damage in vivo. With the goal of eventual clinical use of HB-EGF to protect the intestines from injury in neonates, children, and adults, the pharmacokinetics and biodistribution of 125I-labeled HB-EGF were investigated. After intravenous bolus, HB-EGF had a distribution half-life of 0.8 min and an elimination half-life of 26.67 min. After gastric administration, the bioavailability was 7.8%, with a 2.38 h half-life in the absorption phase and an 11.13 h half-life in the elimination phase. After intravenous dosing, most radioactivity was found in the plasma, liver, kidneys, bile, and urine, whereas it was mainly distributed in the gastrointestinal tract after intragastric administration. The degradation of 125I-HB-EGF in plasma from newborn rats was lower than that in adult rats after gastric administration. This supports the feasibility of enteral administration of HB-EGF in the treatment of gastrointestinal diseases, including newborns afflicted with necrotizing enterocolitis.
 ...
PMID:Tissue distribution and plasma clearance of heparin-binding EGF-like growth factor (HB-EGF) in adult and newborn rats. 1636

Necrotizing enterocolitis (NEC) is a disease process that is frequently seen in the neonatal intensive care unit (NICU) and in preterm newborns. The pathophysiology of NEC is a detailed multifactorial theory that will not be thoroughly discussed in this article. The key risk factors leading to NEC are prematurity, formula feeding, intestinal ischemia, and bacterial colonization. Current research regarding feeding practices, surgical techniques, bowel transplantation, and use of probiotics is presented to update NICU nurses on the state of the science of care for the newborn with NEC. Caring for the sick neonate involves holistic family care. Listening to and supporting parents through the stressful stay in the NICU can empower them to be better prepared and educated to take their newborns home.
 ...
PMID:NICU update: state of the science of NEC. 1650 62


<< Previous 1 2 3 4 5 6 7 8 9 10