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

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.
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PMID:Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model. 1147 51

We experienced an extremely low birth weight (ELBW) infant complicated with pulmonary atresia and necrotizing enterocolitis. She was born at 25 weeks of gestation with a birth weight of 752 g. Five hours after birth, she manifested cyanosis and was diagnosed as having pulmonary atresia with intact ventricular septum (PAIVS). Infusion of lipo-prostaglandin E1 (PGE1) was started to keep the ductus open along with infusion of dopamine and dobutamine. At 8 days of life she developed hypotension and metabolic acidosis, and the diagnosis of intestinal perforation was made by free air in the abdomen. The excessive shunt flow to the pulmonary vasculature via the ductus was suspected to have caused an inadequate systemic flow leading to the intestinal ischemia and necrotizing enterocolitis. Lipo-PGE1 was discontinued to decrease the shunt flow through the ductus. Brock's operation (closed transventricular pulmonary valvotomy) was performed at the age of 8 and 11 days and the ligation of the ductus arteriosus was performed at the age of 13 days. Propranolol was administered to inhibit the pulmonary outflow tract constriction along with catecholamines to stabilize hemodynamics. She recovered slowly and her trachea was extubated at 58 days of life.
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PMID:[An extremely low birth weight infant with pulmonary atresia complicated with necrotizing enterocolitis]. 1171 52

Cocaine has become a popular illicit drug in our society, and pregnant women are not immune from this epidemic. Recently, there have been several references in the literature describing an association between prenatal cocaine exposure and the subsequent development of necrotizing enterocolitis in the neonate, but the mechanism underlying this relationship remains speculative. Because alpha-2 adrenergic receptors are thought to play a role in the autoregulatory mechanism in the newborn intestine that responds to hypoxia and ischemia, we examined the expression of this receptor in the intestine of embryonic rats exposed to low- and high-dose cocaine in utero. Pregnant Sprague Dawley rats were injected daily with either saline, low-dose cocaine, or high-dose cocaine beginning on embryonic d 5 (E 5) and continuing to E 20. Mothers were killed on E 16, E 17, E 18, E 19, and E 20. Embryos were frozen and stored at -80 degrees C. In situ hybridization was performed on 20- micro m sections with 35S-labeled oligonucleotide probes specific for the alpha-2A adrenergic receptor subtype. Densitometric analysis revealed a significant decrease in the alpha-2A receptor expression in the intestine of both the low-dose and high-dose cocaine-exposed animals compared with controls. This down-regulation was demonstrated by E 17, and continued through the remainder of gestation. These changes may limit the normal adaptation to vasoconstriction, thus exacerbating the already insufficient compensatory mechanisms for responding to ischemic injury, and thus may be one of the important factors predisposing cocaine-exposed infants to necrotizing enterocolitis.
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PMID:Alpha-2A adrenergic receptor subtype gene expression in the intestines of cocaine-exposed rat embryos. 1235 43

In a current publications, it has been suggested that hypoxia-triggered "good angiogenesis" involving hypoxic up-regulation of vascular endothelial growth factor (VEGF) molecules, genes, and receptors is likely responsible in a major way for the remarkable gut and patient salvage experience associated with use of the "patch, drain, and wait" (PD&W) surgical approach to perforated necrotizing enterocolitis and midgut volvulus (MGV) with extensive ischemia/necrosis. We report a case in which extensive ischemia/necrosis in a newborn with gastroschisis (likely MGV-induced) was managed successfully by PD&W with an associated marked (24-fold) elevation of VEGF in drainage fluid at 7 days post-initiation of PD&W.
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PMID:Marked (24-fold) elevation of peritoneal cavity drainage fluid vascular endothelial growth factor after successful "patch, drain, and wait" approach for extensive midgut necrosis in a newborn. 1241 65

Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.
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PMID:Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. 1242 5

The diagnosis of necrotizing enterocolitis (NEC) is made from a combination of clinical and radiographic findings. There are no useful screening biochemical markers of intestinal injury. The serum concentration of cytosolic beta-glucosidase (CBG), an enzyme found primarily in enterocytes, is markedly elevated in animal models of ischemia and bowel obstruction. We hypothesized that in a rat model of NEC, serum CBG activity would significantly increase before microscopic evidence of severe intestinal injury. Cohorts of 2-wk-old Sprague-Dawley rats (n = 10/cohort) were anesthetized and underwent laparotomy with occlusion of the superior mesenteric artery (SMA). Platelet-activating factor (200 microg/animal) was injected in the proximal duodenum. Serum and intestinal samples were obtained at time 0 (control) and 30, 60, and 90 min of ischemia (I) and after 90 min of I followed by 60 min of reperfusion (I/R). Histopathologic injury was categorized as either no or minimal injury or mural necrosis by two masked investigators and CBG activity was measured by ELISA. Data were analyzed with Fisher's exact test and ANOVA. Only the I/R group had significantly greater mural necrosis compared with the control group (90% versus 0%, respectively, p < 0.001). In contrast, CBG activity was significantly elevated after only 90 min of I and after I/R (15.1 +/- 5.6 and 16.4 +/- 4.3 units/mL, respectively, p < 0.05). We conclude that serum CBG is elevated before transmural intestinal injury in this model and may have utility as an early marker of ischemia in patients at risk for NEC.
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PMID:Serum cytosolic beta-glucosidase activity in a rat model of necrotizing enterocolitis. 1286 98

The term spontaneous intestinal perforation suggests a perforation in the gastrointestinal tract of a newborn of no demonstrable cause. Only a few cases have been described in full-term newborns. The aetiology and pathogenesis of the disease are unknown although multiple theories have been proposed. Some authors suggest ischemia as the most likely cause. Conditions associated with fetal or neonatal hypoxia are important antecedents for this emerging distinct entity. We present a case of a spontaneous, intestinal perforation in a full-term neonate with urinary tract infection. There was no clinical evidence of necrotizing enterocolitis or bowel obstruction. Radiological images revealed a pneumoperitoneum. An emergency explorative laparotomy was performed. A localized linear perforation was identified in the transverse colon. Pathological examination of the resected specimens failed to reveal any etiology for the perforation. The neonate recovered rapidly, with no gastrointestinal complications. In our case none of the factors which have previously been associated with intestinal perforation could be implicated. We suggest that focal intestinal perforation is possibly the result of infection. Further studies, including careful recording of cases and close histopathological examination of resected specimens, are required in order to provide more information and improve our understanding of the aetiology of this rare occurance.
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PMID:Spontaneous intestinal perforation in a full-term infant: association with infection. 1290 Jul 15

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered to be a major contributing factor. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R. Some reports revealed that infants with NEC and perforated bowel can completely recover with drainage alone. This study aims to assess the ability of newborn rat intestine to resist apoptosis after I/R injury compared with adult rat intestine. Intestines from 10 groups of rats (n = 6 for each study group) were studied: (1) normal control group; (2) ischemia group, receiving vascular occlusion for 60 min; (3) I/R groups receiving vascular occlusion for 60 min and reperfusion for 15, 30, and 60 min, respectively. Apoptosis was quantified by TUNEL methods. Statistical analysis was performed using ANOVA with Dunn's test. TUNEL-positive cells per 10 crypts were significantly increased in the ischemia and I/R groups compared to the control group. The peak number of positive cells by TUNEL was recognized 30 min after reperfusion in adult and newborn rats and then reduced gradually. The newborn rats had significantly less TUNEL-positive cells per 10 crypts than adult rats subjected to I/R injury (p < 0.05). We demonstrated that the activation of apoptosis occurred after intestinal I/R injury, especially during the reperfusion phase. The newborn intestine was more resistant to I/R injury and thus may have significant clinical application.
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PMID:Reduced apoptosis in newborn compared to adult rat intestine after ischemia-reperfusion injury. 1463 Nov 54

Many patients with sepsis have bacteremia for which no septic focus is identified either clinically or by autopsy. This study was designed to determine the relationship between the ischemia-reperfusion injury (IRI) and bacterial translocation that might be involved in the pathogenesis of necrotizing enterocolitis. In the first experiment, a total of 32 Sprague-Dawley rats weighing 150-200 g were divided into four groups. The mesentery to isolated loop was occluded for 30, 60, and 90 min following 30-min reperfusion in the three groups of experimental animals with a micro-bulldog clamp. A control group involved the same technique and exposure, without occlusion of the mesentery. Two sets of blood culture were taken through a catheter in the portal vein immediately and 15 min after the reperfusion, respectively. In another experiment, bacteria isolated were fed in different doses to control rats and those after 30- or 60-min ischemia and 30-min reperfusion. Two sets of blood culture were taken following the procedure. Invasion and transcytosis of the bacteria through epithelial cells were studied in vitro using a Madin-Derby canine kidney (MDCK) cell monolayer model. PCR for delta toxin gene was performed on all bacteria isolated, using Staphylococcus epidermidis as the control. Coagulase-negative staphylococci (CoNS) were invariably isolated from mice with prolonged ischemia (90 min) and reperfusion. When bacteria were fed into mice with only 30-min ischemia, an inoculum as low as 5 x 10(5) CFU/ml could induce bacteremia. No bacterial translocation was found in control mice even fed with a higher dose of bacteria (5 x 10(8) CFU/ml). In vitro experiments showed that CoNS failed to transcytose MDCK monolayer. These isolates were not cytotoxic to MDCK cells and contained no delta toxin gene. Bacterial translocation of CoNS occurred following severe bowel ischemia and reperfusion injury. Intact mucosa integrity readily prevented bacterial translocation; however, bacterial translocation could occur in rats following mild IRI in the presence of a higher number of CoNS in the gut.
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PMID:Translocation of coagulase-negative bacterial staphylococci in rats following intestinal ischemia-reperfusion injury. 1464 38

Intestinal ischemia/reperfusion (I/R) injury affects patients of different ages, especially premature babies and the elderly. The outcome after intestinal I/R is often dismal, which may be attributed to loss of the barrier and immune functions of the intestines, as well as development of secondary injury in remote organs. The available treatment for advanced gut ischemia mandates extensive resection, which may cause growth retardation in infants and nutritional problems in the elderly. Throughout the past decade we have been investigating the potential therapeutic role of heparin-binding epidermal growth factor-like factor (HB-EGF) in intestinal I/R. The mitogenic and chemoattractant functions of HB-EGF formed the initial rationale for our investigations. In addition, HB-EGF is a potent antiapoptotic protein that enables cells and tissues exposed to different apoptotic stimuli to survive hypoxic, oxidative, and nutritional stresses. HB-EGF is known to have a vital role in wound healing and postischemic regeneration in different organs. In the current review, we summarize the results of our findings of the beneficial effects of HB-EGF in intestinal I/R, supported by additional evidence from the literature and an explanation of different possible mechanisms of its actions. Collectively, the data strongly suggest a potential therapeutic role for the use of HB-EGF to treat intestinal ischemic diseases such as I/R and necrotizing enterocolitis.
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PMID:Heparin-binding epidermal growth factor-like growth factor and intestinal ischemia-reperfusion injury. 1476 65


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