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)

The aim of this study was to detect early renal changes in the rat. Female Wistar rats received oral doses of cyclosporine (12.5, 25 or 50 mg/kg daily). The duration of the experiment was 1, 2, and 3 weeks. Controls received the vehicle only (olive oil). The following alterations were seen by light microscopy: Hypertrophy of the juxtaglomerular apparatus (PAS stain). Cytoplasmic droplets of neutral fat (Oil Red 0) in clusters of cortical tubules, probably belonging to the same nephron. Both the above phenomena increased with dosage and duration of treatment and were absent in controls. In the fat containing tubulus (FCT) brush border staining (alkaline phosphatase) was decreased or absent. Since after PAS the brush border was visualized in many FCT, it is concluded that many FCT were proximal tubulus (PT) of which the brush border has been damaged. In FCT mitochondrial staining (Cytochrome oxidase activity) was strongly decreased or absent. Mean lysosomal volume (acid phosphatase and dipeptidase II) is increased in the PT; in some cyclosporine animals, lysosomes were enlarged, while in others they were comparable to controls. Electron microscopy showed in some PT cells an increased number of empty vacuoles and focal alteration of mitochondria. Normal mitochondria were present next to grossly altered mitochondria. Autophagocytosis of mitochondria was clearly present. The lysosomes appeared swollen and contained electron dense material, not organised in the typical 50 A pattern of myeloid figures. These morphological changes suggest a defect of mitochondrial metabolism, leading to lipid deposition in PT. The mitochondrial metabolism can be disturbed by a direct toxic effect of cyclosporine or indirectly via ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies. 301 37

A prospective study of 17 patients with fracture neck of femur was undertaken to study the vascularity of the femoral head by bone scan using Technetium-99m MDP, as well as to study the viability of the femoral head by histopathology, and therefore determine correlation, if any, between these two methods. Treatment was by primary endoprosthetic replacement (Moore's Arthroplasty). In 16 of the 17 patients the bone scan showed decreased vascularity of the head, but histopathological examination could not confirm non-viability of the head. It is likely that, since the majority of the patients were operated on within 4 days, there was insufficient time for histopathological evidence of ischemia to develop, prior to removal of the femoral heads.
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PMID:Assessment of vascularity of head of femur by bone scan and histopathology. 356 72

In eight undisplaced intracapsular fractures of the femoral neck, an intracapsular hematoma was diagnosed by computed tomography. 99mTc-MDP scintimetry revealed markedly reduced or absent blood supply to the head of femur. The intracapsular pressure was 23 (2.7-43) kPa with the hip in neutral position. Following aspiration of 12 (0.5-36) ml of blood, pressure was reduced to zero, and postaspiration scintimetry revealed restitution of blood supply to the femoral head. Hip joint tamponade in these patients has caused femoral head ischemia, reversible by aspiration.
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PMID:Hemarthrosis in undisplaced cervical fractures. Tamponade may cause reversible femoral head ischemia. 378 90

Early and accurate diagnosis of infection or neuropathy of the diabetic foot is the key to successful management. Angiopathy leads to ischemia which, in combination with peripheral neuropathy, predisposes to pedal skin ulceration, the precursor of osteomyelitis. Chronic hyperglycemia promotes production of glycosylated end products which accumulate on endothelial proteins, causing ischemia of the vasa nervorum. When combined with axonal degeneration of the sensory nerves, the result is hypertrophic neuroarthropathy. Should the sympathetic nerve fibers also be damaged, the resultant loss of vasoconstrictive impulses leads to hyperemia and atrophic neuroarthropathy. Plain radiography, although less sensitive than radionuclide, magnetic resonance (MR), and computed tomographic examinations, should be the initial procedure for imaging suspected osteomyelitis in the diabetic patient. If the radiographs are normal but the clinical suspicion of osteomyelitis is strong, a three-phase 99mTc-MDP scan or MR imaging is recommended. An equivocal 99mTc-MDP scan should be followed by MR imaging. To exclude osteomyelitis at a site of neuroarthropathy, a 111In white blood cell scan is preferable. To obtain a specimen of bone for bacteriological studies, percutaneous core biopsy is the procedure of choice, with the entrance of the needle well beyond the edge of the subjacent ulcer.
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PMID:Imaging the diabetic foot. 861 54

To assess the role of scintigraphic evaluation of distal limb perfusion, the medical records and scintigraphic perfusion images of 17 animals (8 dogs, 2 cats, 2 calves, 4 birds and 1 ferret) with clinical signs of distal limb ischemia were examined retrospectively. Images were obtained at 5 and 10 minutes following injection of 99mTc-MDP, or 99mTc-DTPA. The initial scintigraphic diagnoses of 17 animals included complete ischemia (8/17), partially reduced perfusion (5/17), and normal to increased perfusion (4/17). In 4 of the animals with partially reduced perfusion, follow-up scans indicated progression to complete ischemia (1/4) or normal to increased perfusion (3/4). Nine of 17 animals had a final scintigraphic diagnosis of complete distal limb ischemia, and these animals were either euthanized (5/9) or had limb amputation (4/9). A final diagnosis of complete ischemia was supported with either repeat scanning (3/10), continued clinical observation (6/10) and/or pathological examination (10/10). Clinical signs of ischemia resolved in all (7/17) animals with increased or normal perfusion on their final scan. Scintigraphy provided a safe and noninvasive assessment of distal limb perfusion, which corresponded with clinical outcome.
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PMID:Scintigraphic assessment of distal extremity perfusion in 17 patients. 923 93

There is evidence that dietary polyunsaturated fatty acids (PUFA) may protect against cardiovascular diseases, but the involvement of the cardiac muscle cell in this beneficial action remain largely unknown. The present study compared the respective influence of n-3 and n-6 PUFA on the function of cultured neonatal rat cardiomyocytes (CM). Cells were grown for 4 days in media enriched either n-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) or n-6 (arachidonic acid, AA) PUFA. The PUFA n-6/n-3 ratio in the phospholipids was close to 1 and 20 in the n-3 and n-6 cells, respectively. The transmembrane potentials were recorded using microelectrodes and the contractions were monitored with a photoelectric device. In physiological conditions, the increase of n-6 PUFA level in the phospholipids resulted in a significant decrease in the maximal rate of initial depolarization (-16%). In opposition, the action potential amplitude and duration were not altered, and the cell contraction outline was not affected. Ischemia was simulated in vitro using a substrate-free, hypoxia-reoxygenation procedure in a specially designed gas-flow chamber. The progressive loss of electrical activity induced by the substrate-free, hypoxic treatment was affected by the n-6/n-3 ratio, since the n-6 rich CM displayed a slower depression of the AP amplitude and duration parameters. Conversely, the recovery of the resting potential (MDP) during reoxygenation was faster in n-3 CM, whereas the recovery of the contraction parameters was unaffected by the fatty acid composition of the cells. These results suggested that, in physiological conditions, the modification of long chain PUFA balance in the phospholipids of cardiac muscle cells may modulate the initial AP upstroke, which is governed by sodium channels. Moreover, the presence of n-3 PUFA appeared to accelerate the electrical depression during substrate-free hypoxia but in turn to allow a faster recovery upon reoxygenation.
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PMID:Influence of phospholipid long chain polyunsaturated fatty acid composition on neonatal rat cardiomyocyte function in physiological conditions and during glucose-free hypoxia-reoxygenation. 935 58

Mucosal pH abnormalities are associated with anastomotic dehiscence, ischemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation and studied extracellular pHo (7.0-8.5) effects on human (Caco-2) intestinal epithelial motility, proliferation, and differentiation. Mucosal healing was modeled by sheet migration and differentiation by alkaline phosphatase and dipeptidyl dipeptidase specific activity. In parallel differentiation and motility studies, we inhibited proliferation with mitomycin to dissociate indirect mitogenic effects. Intracellular pHi was quantitated using BCECF/AM at varying extracellular pHo and in migrating cells. Motility was maximal at pHo 7.6 and proliferation at 7.2. Each decreased with acidity and alkalinity. By contrast, brush border enzyme activity was lowest at pHo 7.0 and highest at pHo 8.5. pHi was highest at pHo 8.5. Migrating cell pHi was higher than static cell pHi. Thus, extracellular pHo deviations perturb Caco-2 pHi homeostasis and motility. Alkalinity promotes differentiation while acidity induces proliferation and limits differentiation.
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PMID:Differential effects of mucosal pH on human (Caco-2) intestinal epithelial cell motility, proliferation, and differentiation. 969 Mar 92

We have evaluated the effects of the N-acetylated-alpha-linked acidic dipeptidase (NAALADase) inhibitor, GPI5232 [2-[(pentafluorophenylmethyl)hydroxyphosphinyl]methyl)-pentanedioic acid], to not only decrease brain injury but also to alter the inherent electroencephalographic (EEG) changes observed in a rat model of transient middle cerebral artery occlusion (MCAo). Continuous i.v. infusion of GPI5232 starting 1 h after injury resulted in more than a 50% reduction in brain infarct volume caused by 2 h of MCAo. This effect was dose-dependent and significant even when first treatment was delayed for 2 h post-MCAo. At 24 h post-MCAo, EEG spectral analysis of the injured hemisphere revealed functional improvement in GPI5232-treated rats. Significant recovery in high-frequency EEG power (8-30 Hz) was measured in GPI5232-treated animals in both parietal and temporal brain regions but not in vehicle-treated animals. MCAo-injured rats were also predisposed to developing cortical brain seizures, and GPI5232-treated rats had significantly fewer brain seizures than vehicle-treated animals. In separate experiments, acute high doses of GPI5232 in normal rats did not significantly alter EEG brain activity as evaluated by spectral analysis and did not produce any signs of seizure activity or behavioral abnormalities. These results show GPI5232 to be an effective neuroprotective treatment when given postinjury by reducing brain infarction and ameliorating the pathological EEG associated with focal brain ischemia.
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PMID:Electroencephalogram analysis and neuroprotective profile of the N-acetylated-alpha-linked acidic dipeptidase inhibitor, GPI5232, in normal and brain-injured rats. 1156 Oct 62

Inhibition of glutamate carboxypeptidase (GCP) II (EC 3.4.17.21), also termed N-acetylated alpha-linked acidic dipeptidase (NAALADase), has been shown to protect against ischemic injury presumably via decreasing glutamate and increasing N-acetyl-aspartyl-glutamate (NAAG). NAAG is a potent and selective mGlu3 receptor agonist. Activation of glial mGlu3 receptors has been shown to protect against NMDA toxicity by releasing transforming growth factors, TGF-betas. We hypothesized that GCP II inhibition could be neuroprotective also via TGF-betas, due to increased NAAG. To verify this, Enzyme-Linked Immunosorbent Assays (ELISAs) were performed on media from both control and ischemic cultures treated with the GCP II inhibitor, 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). We found that 2-PMPA attenuated ischemia-induced declines in TGF-beta. To further assess the role of TGF-betas in 2-PMPA-mediated neuroprotection, a neutralizing antibody to TGF-beta (TGF-beta Ab) was used. In both in vitro and in vivo models of cerebral ischemia, TGF-beta Ab reversed the neuroprotection by 2-PMPA. Antibodies to other growth factors had no effect. Data suggests that neuroprotection by GCP II inhibition may be partially mediated by promoting TGF-beta release.
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PMID:Neuroprotection mediated by glutamate carboxypeptidase II (NAALADase) inhibition requires TGF-beta. 1169 60

Neuroprotective effects of N-acetylaspartylglutamate (NAAG), the precursor of glutamate and a selective agonist at the Group II metabotropic glutamate (mGlu) receptor, against hypoxic-ischemic brain injury were examined in a neonatal rat model of cerebral hypoxia-ischemia. The neonatal hypoxia-ischemia procedure (unilateral carotid artery ligation followed by exposure to an 8% oxygen hypoxic condition for 1.5 h) was performed in 7-day-old rat pups. Following unilateral carotid artery ligation, NAAG (0.5 to 20 mg/kg, i.p.) was administered before or after the hypoxic exposure. Brain injury was examined 1-week later by weight reduction in the ipsilateral brain and by neuron density in the hippocampal CA1 area. In the saline-treated rat, neonatal hypoxia-ischemia resulted in severe brain injury as indicated by a 24% reduction in the ipsilateral brain weight. Low doses of NAAG (2-10 mg/kg, but not 0.5 mg/kg), administered before or even if 1 h after the hypoxic exposure, greatly reduced hypoxia-ischemia-induced brain injury (3.8-14.2% reduction in the ipsilateral brain weight). A high dose of NAAG (20 mg/kg) was ineffective. While L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) and trans-[1S,3R]-1-Amino-cyclopentane-1, 3-dicarboxylic acid (t-ACPD) were unable to provide protection against hypoxic-ischemic brain injury, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), an inhibitor of N-acetylated alpha-linked acidic dipeptidase (NAALADase), which hydrolyzes endogenous NAAG into N-acetyl-aspartate and glutamate, significantly reduced neonatal hypoxia-ischemia-induced brain injury. (alphaS)-alpha-Amino-alpha-[(1S, 2S)-2-carboxycyclopropyl]-9H-xanthine-9-propanoic acid (LY341495), a selective antagonist at the mGlu2/3 receptor, prevented the neuroprotective effect of NAAG. Neuron density data measured in the hippocampal CA1 area confirmed that ipsilateral brain weight reduction was a valid measure for hypoxic-ischemic brain injury. Neonatal hypoxia-ischemia stimulated an elevation of cyclic AMP (cAMP) concentration in the saline-treated rat brain. NAAG, L-AP4 and t-ACPD all significantly decreased hypoxia-ischemia-induced elevation of cAMP. LY341495 blocked the effect of NAAG, but not of L-AP4 or t-ACPD, on hypoxia-ischemia-stimulated cAMP elevation. The overall results suggest that the neuroprotective effect of NAAG is largely associated with activation of mGlu2/3 receptor.
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PMID:Neuroprotective effects of N-acetylaspartylglutamate in a neonatal rat model of hypoxia-ischemia. 1189 Sep 1


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