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)

Changes in biochemical and electroencephalographic parameters were followed over time during the development of acute hepatic encephalopathy (HE) in two different experimental models. In the rat, (sub)acute liver failure was obtained either by ligation of the hepatic artery in previously portacaval-shunted animals or by intraperitoneal injection of a high dose of galactosamine (GALN). The EEG changes were characterized in both models by a significant increase in low-frequency activity of the EEG power density spectra: the so-called 'left shift'. This 'left shift' was significant in liver ischemia after 4-5 h and in GALN hepatitis after about 30 h. The changes in plasma biochemical indices also showed a great similarity in both models. The concentration of all measured plasma amino acids (except histidine and arginine in GALN hepatitis and arginine in liver ischemia), NH3 and ALAT were significantly increased during the development of (sub)acute HE. Correlation of the combined data of electroencephalographic and biochemical indices showed a significant (P less than 0.01) correlation between the 'left shift' and NH3, taurine, threonine, proline, alanine, methionine, cystathionine, phenylalanine, tryptophan, ornithine and histidine. It is concluded that EEG spectral analysis is a useful parameter for following the development of (sub)acute hepatic encephalopathy in relation to biochemical parameters.
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PMID:Correlation between electroencephalographic and biochemical indices in acute hepatic encephalopathy in rats. 359 63

Rat slow-twitch muscle, in contrast to fast-twitch muscle, maintains its ATP content near normal during intense stimulation conditions that produce rapid fatigue. An extensive depletion of adenine nucleotide content by the deamination of AMP to IMP + NH3, typical of fast-twitch muscle, does not occur. We evaluated whether this response of slow-twitch muscle could be simply due to failure of synaptic transmission or related to cellular conditions influencing enzyme activity. Stimulation of soleus muscles in situ via the nerve or directly in the presence of curare at 120 tetani/min for 3 min resulted in extensive fatigue but normal ATP contents. Thus the lack of ATP depletion must be related to cellular events distal to neuromuscular transmission. Even nerve and direct muscle stimulation (with curare) during ischemia did not cause a large depletion of ATP or a large elevation of lactate content (12.0 +/- 0.7 mumol/g), even though the decline in tension was essentially complete. However, if the same tension decline during ischemia was prolonged by stimulating for 10 min at 12 tetani/min a large decrease in ATP (2.24 +/- 0.09 mumol/g) and increase in IMP (2.47 +/- 0.16 mumol/g) and lactate (30.4 +/- 2.0 mumol/g) content occurred. Thus adenine nucleotide deamination to IMP can occur in slow-twitch muscle during specific contraction conditions. The cellular events leading to the activation of AMP deaminase require an intense contraction condition and may be related to acidosis caused by a high lactate content.
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PMID:ATP depletion in slow-twitch red muscle of rat. 363 Dec 51

Experimental acute liver ischemia in pigs induces an increment in plasma free tryptophan with decreased total tryptophan. Brain tryptophan is elevated in all brain areas. A slight, but significant increase of brain serotonin is demonstrated in the striatum only, while 5-HIAA (5-hydroxyindoleacetic acid) is significantly lower in the hypothalamus. Other brain areas do not show significant changes in serotonin and 5-HIAA levels. Neither the high plasma free tryptophan levels, nor the decreased sum of neutral competitive amino acids are consistent with such an elevation of brain tryptophan. Hemodialysis was carried out with two different kinds of membranes: cuprophan (with an efficient removal of molecules up to molecular weight 1300) and AN 69 polyacrylonitrile (efficient removal up to 15,000). Ammonia and aminoacid clearance are similar for both membranes. After AN 69, plasmatic free tryptophan and brain tryptophan are lower than after liver devascularization, but still higher than normal. Serotonin significantly increases in the cortex, midbrain and hypothalamus without concomitant rise of 5-HIAA levels. After cuprophan hemodialysis, plasma total tryptophan is lower than in normal and even comatose animals, whereas free tryptophan is normal. Intracerebral tryptophan is similar to AN 69 dialysed animals, but in the hypothalamus it is similar to nondialysed animals. Brain serotonin levels are not modified. 5-HIAA decreases in the hypothalamus. This finding suggests that middle molecules (which are not cleared out with cuprophan hemodialysis) are involved in the intracerebral transfer of tryptophan and the metabolism of serotonin, mainly in the hypothalamus.
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PMID:Relationship between plasma and brain tryptophan in pigs during experimental hepatic coma before and after hemodialysis with selective membranes. 616 12

The aim of this paper is to elucidate the cause of death after 90 min of normothermic partial (2/3) ischemia of the liver and to examine the effects of glucagon, somatostatin, insulin, prednisolone and oral administration of polymyxin B (PB). The animals 24 hr after partial ischemia for 90 min were divided into two groups; namely, animals with normal appearance and those with moribund state. There were no significant differences in the plasma level of S-GOT, S-GPT, amino acids, NH3 or insulin, or in morphometrically estimated volume ratio of necrotic hepatocytes between the two groups of rats. The blood glucose level, however, was significantly decreased (31 +/- 28 mg/100 ml, n = 6) in the moribund rats with a higher incidence of positive Limulus gelation tests as compared with the rats with normal appearance (149 +/- 19, n = 5). The 1-day and 1-week survival rates of the animals were 42/62 (69%) and 32/61 (53%), respectively. A glucagon injection (1.5 mg/kg, after ischemia) was effective to elevate the 1-day survival rate (14/14), but failed to increase the 1-week survival rate (11/14). On the other hand, a somatostatin injection (100 micrograms/kg, after ischemia) or PB treatment (15 mg/kg/day x 5-9, before ischemia) succeeded to increase the 1-week survival rate (20/22 p less than 0.01 and 17/17 p less than 0.01, respectively), although no significant amelioration in transaminase levels or volume ratio of necrosis was demonstrated. It could be seen that a moribund state after partial ischemia was accompanied by severe hypoglycemic shock, and that the injection of somatostatin after ischemia or the annihilation of gram-negative bacteria by means of oral administration of polymyxin B before ischemia prevented the occurrence of the hypoglycemic shock.
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PMID:Postischemic liver damage in rats: effect of some therapeutic interventions on survival rate. 629 17

To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with N-13, and of C-11-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all N-13 AA, and three (early, intermediate, late) for the two C-11 compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for N-13-labeled Ala, Glu, Asp, and Leu, but not for N-13 Gln and C-11 compounds. Transaminase inhibition shortened the half-times of the late phases of N-13-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of N-13 Gln and C-11 Oxal; and resulted in a loss of C-11 CO2 production and of the intermediate phase for C-11 Asp. On the PCT images, N-13 activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by N-13 NH3 imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia.
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PMID:Evaluation of myocardial metabolism, with N-13- and C-11-labeled amino acids and positron computed tomography. 698 Sep 71

Recent studies have indicated that ammonia is involved in the pathophysiology of Helicobacter pylori-associated gastric mucosal damage. Helicobacter pylori-associated chronic active gastritis is characterized by an invasion of neutrophils. We investigated the interrelationship among hypochlorous acid (oxidant produced by neutrophil), ammonia (product of Helicobacter pylori urease), and monochloramine (product of ammonia and hypochlorous acid) in the development of gastric mucosal damage in rats. Gastric mucosal lesions were produced by exposure of the gastric mucosa to ammonia, urea with urease, or urea with Helicobacter pylori in rats subjected to ischemia. Pretreatment with taurine (scavenger of hypochlorous acid) or antineutrophil serum significantly attenuated gastric mucosal lesions induced by the above test agents. Ammonia-induced gastric mucosal lesions were exacerbated in the presence of hypochlorous acid with concomitant generation of monochloramine. These results suggest that the ammonia, hypochlorous acid, and monochloramine triad may be important in Helicobacter pylori-mediated gastric mucosal damage.
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PMID:Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage. 785 Nov 88

Astrocytes are important in regulating the microenvironment of neurons both by catabolic and synthetic pathways. The glutamine synthetase (GS) activity observed in astrocytes affects neurons by removing toxic substances, NH3 and glutamate; and by providing an important neuronal substrate, glutamine. This glutamate cycle might play a critical role during periods of hypoxia and ischemia, when an increase in extracellular excitatory amino acids is observed. It was previously shown in our laboratory that fructose-1,6-bisphosphate (FBP) protected cortical astrocyte cultures from hypoxic insult and reduced ATP loss following a prolonged (18-30 hrs) hypoxia. In the present study we established the effects of FBP on the level of glutamate uptake and GS activity under normoxic and hypoxic conditions. Under normoxic conditions, [U-14C]glutamate uptake and glutamine production were independent of FBP treatment; whereas under hypoxic conditions, the initial increase in glutamate uptake and an overall increase in glutamine production in astrocytes were FBP-dependent. Glutamine synthetase activity was dependent on FBP added during the 22 hours of either normoxic- or hypoxic-treatment, hence significant increases in activity were observed due to FBP regardless of the oxygen/ATP levels in situ. These studies suggest that activation of GS by FBP may provide astrocytic protection against hypoxic injury.
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PMID:Effect of fructose-1,6-bisphosphate on glutamate uptake and glutamine synthetase activity in hypoxic astrocyte cultures. 791 Mar 81

We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.
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PMID:[Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat]. 795 22

The determination of total serum bile acids (BA) is a sensitive variable for detection of altered liver function. This study investigated the course of serum bile acids in 44 liver-resected patients with different factors possibly compromising liver function. These factors were 1) amount of resected parenchyma; 2) duration of intraoperative ischemia; and 3) patient's age. The course of BA was compared with that of transaminases, bilirubin, lactate, and NH3. Serum BA showed a course correlated to the amount of resected liver parenchyma and differentiated between groups with < or = 35% and > 35% resected parenchyma. Whereas BA were more accurate in paralleling the resected tissue in the first postoperative days, a rise of bilirubin indicated complications in the postoperative course. As BA did not increase in a case of pulmonary-induced multiorgan failure, the specificity of this variable for liver function is implied. Different amounts of resection could not be distinguished by determination of transaminases. Different ischemic periods did not result in significant differences in the postoperative course of BA or bilirubin. However, marked elevations of transaminases depending on the duration of hepatic inflow occlusion were seen. None of the traced variables were related to the patient's age.
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PMID:Postoperative course of functional and cellular variables in liver resection. 828 29

We have identified a new putative transcription factor from the rat kidney, termed Kid-1 (for kidney, ischemia and developmentally regulated gene 1). Kid-1 belongs to the C2H2 class of zinc finger genes. Its mRNA accumulates with age in postnatal renal development and is detected predominantly in the kidney. Kid-1 mRNA levels decline after renal injury secondary to ischemia or folic acid administration, two insults which result in epithelial cell dedifferentiation, followed by regenerative hyperplasia and differentiation. The low expression of Kid-1 early in postnatal development, and when renal tissue is recovering after injury, suggests that the gene product is involved in establishment of a differentiated phenotype and/or regulation of the proliferative response. The deduced protein contains 13 C2H2 zinc fingers at the COOH end in groups of 4 and 9 separated by a 32-amino-acid spacer. There are consensus sites for phosphorylation in the NH2 terminus non-zinc finger region as well as in the spacer region between zinc fingers 4 and 5. A region of the deduced protein shares extensive homology with a catalytic region of Raf kinases, a feature shared only with TFIIE among transcription factors. To determine whether Kid-1 can modulate transcription, a chimeric construct encoding the Kid-1 non-zinc finger region (sense or antisense) and the DNA-binding region of GAL4 was transfected into COS and LLC-PK1 cells together with a chloramphenicol acetyltransferase (CAT) reporter plasmid containing GAL4 binding sites, driven by either a minimal promoter or a simian virus 40 enhancer. CAT activity was markedly inhibited in cells transfected with the sense construct compared with the activity in cells transfected with the antisense construct. To our knowledge, this pattern of developmental regulation, kidney expression, and regulation of transcription is unique among the C2H2 class of zinc finger-containing DNA-binding proteins.
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PMID:Kid-1, a putative renal transcription factor: regulation during ontogeny and in response to ischemia and toxic injury. 838 78


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