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)

Normothermic rats with 12 min, complete cerebral ischemia were treated with the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxalinedione (NBQX) [10], which prevents CA1 pyramidal neuron loss. Twenty hours after ischemia, cerebral protein synthesis rate (CPSR) was measured autoradiographically using [35S]methionine. Ischemia caused a 38% decrease of CPSR in CA1, and postischemic treatment with NBQX caused a 66% decrease in this region. Also treatment with NBQX alone resulted in a decrease (22% in CA1) of the CPSR. Since some evidence exists that the neuroprotective effect of NBQX is related to blockade of the fast AMPA-mediated transmission, the further decrease of the postischemic CPSR in CA1 could be a mere side effect.
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PMID:Regional cerebral protein synthesis after transient ischemia in the rat: effect of the AMPA antagonist NBQX. 138 88

1. We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage.
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PMID:Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion. 159 23

In 1983, a previously healthy 21-year old mother came to University Hospital in Dijon, France feeling weak and had a severe frontal headache with vomiting. Clinical and biochemical tests were normal. She smoked 20 cigarettes/day and used a high dosed combined oral contraceptive (OC) (ethinyl estradiol and cyproterone acetate). 15 days later, the headache returned and she could not understand spoken words and the bilateral section of the brain had slowed. Yet her mental status was normal as were cerebrospinal fluid and cerebral computerized tomography tests. The antiherpes virus drug, vidabarine, did not alleviate symptoms. At least 1 month later, a severe left pulmonary embolism caused acute right heart failure. She also had a prethrombotic left iliac vein, so physicians began heparin therapy, adding nifedipine and buflomedil to control the spasms in the right internal iliac artery and both external iliac arteries. Acute ischemia of the lower limbs eased within a week but sensory disorders remained for 2 months. Satisfactory collaterality transpired due to a blocked left external iliac artery and left iliac vein. The following signs and symptoms indicated her condition to be homocystinuria: blond hair with deep blue eyes, macrocytic anemia, factor VII deficit (51%), strong positive Brandt's reaction, cystine homocystine in the plasma, and presence of homocystine, cystathionine, and methionine in the urine. Physicians took her off the OC and discharged her on vitamin B6/day, folic acid/day, betaine citrate/day, and the anticoagulant Coumadin. A subsequent check of her 19-year old sister found she had it too. They assessed the patient's condition yearly. In 1988, her left leg developed edema and she limped when not using elastic stockings. Effects of iliac vein phlebitis were evident. She no longer suffered from headaches. Since plasma methionine was within the normal range and homocystine no longer was present in plasma and urine, the physicians halted the anticoagulant therapy. In conclusion, the OC precipitated this partial form of homocystinuria.
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PMID:Vascular manifestations in homocystinuria. 161 Jun 63

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.
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PMID:The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex. 167 7

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.
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PMID:What the clinician can learn from MR glutamine/glutamate assays. 167 85

Primary amyloidosis and myeloma associated amyloidosis causes neuropathy in 10% of the cases, and hemodialysis associated amyloidosis causes carpal tunnel syndrome. However, most severe amyloid neuropathy is observed in familial amyloidotic polyneuropathy (FAP). FAP type I is an autosomal dominant systemic amyloidosis characterized by sensory dominant systemic amyloidosis characterized by dissociated sensory disturbance and autonomic dysfunction. Amyloid deposition is noted universally in endoneurium of peripheral nerve, especially prominent in sural, sciatic nerve, dorsal root ganglia and sympathetic ganglia. Moderate deposition was also noted in dorsal spinal root. Amyloid was absent in CNS. The number of small myelinated fibers is decreased. Unmyelinated axons are severely depleted and amyloid fibrils are observed around the wall of small vessels. Amyloid fibril protein consists of variant transthyretin (TTR:prealbumin) with one amino acid substitution of methionine-for-valine at position 30. Other types of FAP show another one point mutation in TTR molecule. Transgenic mouse model of FAP was produced by microinjecting cloned human variant TTR gene into mice. Amyloid were demonstrated in thyroid, kidney and intestine and so on, but not in peripheral nerve in these mice. Pathogenesis of neuropathy of FAP is not known, but mechanical compression to the nerve, ischemia and metabolic abnormality may play some role combined to cause of nerve fiber damage. The effect of deposition on physiochemical functions of the neuron and mechanism to accumulate in nervous system of the TTR remain to be elucidated.
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PMID:[Amyloid neuropathy]. 196 18

The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease-treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators. In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease-treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats. These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative.
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PMID:Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation. 197 48

Microdialysis combined with a solid-phase radioimmunoassay was used to monitor changes in extracellular opioid peptide levels in the rat globus pallidus/ventral pallidum as a result of terminal brain ischemia. Ischemia was induced by anesthetic overdose or by severance of blood vessels supplying the brain. In control animals the recovered immunoreactivity increased an average of 13-fold in the 30-min sample following anesthetic overdose. Perfusion of a calcium-free, 10 mM EGTA-containing medium through the dialysis probe significantly attenuated the amplitude of this response, with the average increase being only threefold. Shorter sampling intervals (5 min) indicated that release of opioid peptide material into the extracellular environment occurs within the first 5 min of ischemia resulting from severance of the blood supply to the brain. HPLC analysis identified the majority of the postmortem-induced immunoreactive material as Met- and Leu-enkephalin.
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PMID:Postmortem changes in rat brain extracellular opioid peptides revealed by microdialysis. 202 9

This study was designed to determine the effect of cyclocreatine on the release of neutrophil chemotactic factors (NCF) from isolated rabbit hearts. We tested the hypothesis that if ischemia is important for the formation of NCF from the myocardium, then blocking (or delaying) ischemic changes with cyclocreatine should inhibit the release of NCF. Two models were used, including (1) perfusion of rabbit hearts (Langendorff apparatus) with oxygenated (95% oxygen) Krebs-Henseleit buffer (K-H buffer) containing 5% cyclocreatine for 120 minutes, and (2) incubating hearts with phosphate-buffered saline (PBS) containing 5% cyclocreatine for 120 minutes. For both models, rabbits were injected intravenously with 10 ml of 5% cyclocreatine solution 30 minutes before the animals were killed and the hearts removed. Control rabbits were injected with 5% creatine solution or saline for 30 minutes before perfusing hearts with K-H buffer or incubating with PBS. Chemotactic activity was assayed in the perfusates and supernatants using modified Boyden chambers and rabbit peritoneal neutrophils as indicator cells. The chemoattractant f-Met-Leu-Phe (f-MLP) was the positive control for a 100% response rate. Isolated hearts perfused with cyclocreatine showed significantly lower chemotactic activity (ie, 1.24 +/- 1% f-MLP; P less than 0.0001) compared to hearts perfused with K-H buffer (129 +/- 18%) or creatine (227 +/- 42%) (mean +/- standard error). Similar results were obtained using incubated hearts. Next the effect of cyclocreatine on neutrophils in the Boyden chamber was determined and it was found that it did not alter neutrophil migration, which excludes a direct inhibitory effect on the cells. Furthermore supernatant from cyclocreatine-treated hearts did not inhibit neutrophil chemotaxis to C5a, indicating absence of a chemotaxis inhibitor in this preparation. Results of these studies suggest that the observed low activity recovered in perfusate and supernatant of cyclocreatine-treated hearts is a result of reduction in the synthesis and/or release of the factors from myocardial tissues. Similar to previously established data, cyclocreatine treatment significantly preserved myocardial nucleotide levels (ie, adenosine triphosphate and creatine phosphate), which supports our hypothesis that the formation of NCF is ischemia dependent and that maintaining elevated levels of myocardial energy nucleotides reduced chemotactic factor release.
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PMID:Cyclocreatine inhibits the production of neutrophil chemotactic factors from isolated hearts. 224 Jan 67

The average values of the local cerebral glucose utilization (LCGU) were approx. 35-110 mumols/100 g/min in various nuclei in the brain of sham-operated animals. The values, however, were decreased by 25-75% in all areas examined at 24 hr after 4-vessel occlusion (forebrain ischemia) for 0.5 hr. Particularly, the LCGU values in the forebrain nuclei such as the cerebral cortices and thalamus were severely reduced, while that in the nuclei in the midbrain and hindbrain such as the red nucleus, chochlear nucleus and vestibular nucleus were slightly reduced. In rats treated with S-adenosyl-L-methionine (SAM, 100 mg/kg, i.p.) every 1 hr for 6 times from the recirculation, however, the LCGU values were increased in all brain structures by 35-195% in the forebrain ischemic rat. A significant increase was observed in the cerebral neocortices, caudate-putamen, lateral septal nucleus, thalamic nuclei, substantia nigra, cerebellum and some other nuclei. In some forebrain structures whose LCGU were mildly reduced to approx. 60-70% by the ischemia, SAM recovered the LCGU to more than 90% of the value in the sham-operated group. Thus it was concluded that SAM ameliorated widely ischemia-induced reduction of LCGU in the rat.
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PMID:S-adenosyl-L-methionine ameliorates reduced local cerebral glucose utilization following brain ischemia in the rat. 230 34


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