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)

Cystatin C, a cysteine protease inhibitor produced by the choroid plexus and found in CSF at high concentrations, may have an important role in brain injury. We used the two-vessel occlusion model with hypotension to induce transient forebrain ischemia (TFI) in rats for 10 min and then examined cystatin C immuno-like reactivity (CC-IR) after 1, 3, 7 and 14 days of recovery. Our results reveal that CC-IR was minimal or absent in the hippocampus of normal and 1 day post-ischemic animals. However, CC-IR was present in CA1 pyramidal cells and a small number of reactive glia of the stratum radiatum (SR) and stratum oriens (SO) at 3, 7 and 14 days post-ischemia. Histological assessment of the hippocampus indicates that CC-IR was localized in morphologically degenerative neurons. This distinct temporal expression of cystatin C in the rat hippocampus is concurrent with delayed neuronal death following TFI. Thus, these results indicate that cystatin C and/or its substrates may be important components of the post-ischemic neurodegenerative and repair process.
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PMID:Cystatin C, a protease inhibitor, in degenerating rat hippocampal neurons following transient forebrain ischemia. 859 41

The distribution patterns of cystatin C and apolipoprotein E (apo E) were studied immunocytochemically in the gerbil hippocampus before and after 5 min ischemia. In the controls, cystatin C was distributed mainly in astrocytes. In addition, a large number of dots positive for cystatin C were observed around the outlines of neuronal perikarya in the CA1 subfields. One day after ischemia, cystatin C-positive stainings outlining neuronal cell bodies disappeared. On the fourth day, intense stainings for cystatin C appeared in atrophied pyramidal neurons and these stainings in neurons disappeared by the 14th day. A remarkable increase in the number of cystatin C-positive astrocytes occurred on the fourth day and thereafter these spread over the whole of the CA1 subfield. Apo E was also distributed in astrocytes in the control specimens. From the fourth day, extra- and/or intracellular distribution of apo E-immunoreactivities was noted in the stratum pyramidale. Apo E-positive astrocytes disappeared transiently on the fourth day and then reappeared and increased remarkably by the 14th day. These findings indicate that cystatin C and apo E are involved in the degeneration process of brain neuronal cells.
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PMID:Cystatin C and apolipoprotein E immunoreactivities in CA1 neurons in ischemic gerbil hippocampus. 883 51

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder reported worldwide in kindreds with a G654A or G654T gelsolin gene mutation. The clinically characteristic peripheral nerve involvement has been poorly characterized morphologically, and its pathogenesis remains unknown. We studied peripheral nerve and skeletal muscle biopsy or autopsy specimens of 35 patients with a G654A gelsolin gene mutation. Histological, immunohistochemical, and electron microscopic studies showed consistent deposition of gelsolin amyloid (AGel), particularly in the vascular walls and perineurial sheaths. Nerve roots were more severely affected than distal nerves. The amyloid deposits also displayed variable immunoreactivity for apolipoprotein E, amyloid P component, cystatin C, and alpha-smooth muscle actin. Sural nerve morphometry showed preferential age-related large myelinated nerve fiber loss and reduction of myelin sheath cross-sectional area. There was evidence of denervation atrophy and fiber type grouping in skeletal muscle. Our study shows that marked proximal nerve involvement with AGel angiopathy is an essential feature of AGel amyloidosis. The preferential large fiber loss, not generally seen in amyloid neuropathy, may be caused by ischemia due to AGel angiopathy. Deficient actin modulation by variant gelsolin in neurons and Schwann cells, however, may alter axonal transport and myelination and contribute to AGel polyneuropathy.
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PMID:Neuromuscular pathology in hereditary gelsolin amyloidosis. 1207 40

Cystatin C is distributed in all human tissues and fluids with a particular abundance in the cerebrospinal fluid. Cystatin C is a strong endogenous inhibitor of lysosomal cysteine proteases, such as cathepsin B, L, H and S, that are involved in various biological processes such as degradation of cellular proteins and regulation of enzymes, as well as in pathological processes. Pharmacological inhibition of cathepsins has been shown to reduce neuronal damage after brain ischemia, suggesting that cystatin C is an endogenous neuroprotectant. Cystatin C has also amyloidogenic properties and is co-localized with beta-amyloid in degenerated neurons in Alzheimer's disease, suggesting a role in neuronal degeneration. To test the hypothesis that endogenous cystatin C is neuroprotective during brain ischemia, global and focal brain ischemia was induced in mice with the cystatin C gene knocked out. Following focal ischemia, larger brain infarcts were found in cystatin C knockout mice, probably due to a reduced inhibition of the cathepsins during ischemia. In contrast, brain damage after global ischemia was diminished in cystatin C knockout mice, suggesting that cystatin C has an aggravating effect on selective neuronal damage after global ischemia.
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PMID:Gene deletion of cystatin C aggravates brain damage following focal ischemia but mitigates the neuronal injury after global ischemia in the mouse. 1545 Mar 54

Many studies indicate that the hour of the day at which the onset of stroke occurs is very important in patient recovery. Furthermore, multiple studies have been conducted which show that ischemia in rats produces different magnitudes of injury depending on the hour of the day at which it was induced. Using a traumatic brain injury (TBI) model, we analyzed the effect of the time of day on the recovery of rats and obtained a higher survival rate if TBI was induced at 01:00 h as compared with TBI induced at 13:00 h. We also analyzed the effect of the protease inhibitor cystatin C (CC) on the recovery of rats from TBI and found that it increased mortality and bleeding, and that these effects were more pronounced at 13:00 h.
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PMID:Recovery after a traumatic brain injury depends on diurnal variations effect of cystatin C. 1651 99

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.
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PMID:Relation of N-terminal pro B-type natriuretic peptide levels after symptom-limited exercise to baseline and ischemia levels. 1923 20

Urinary neutrophil gelatinase-associated lipocalin (NGAL) may represent an early, predictive biomarker of delayed graft function due to ischemia-reperfusion injury. Unfortunately, creatinine is an unreliable indicator of acute changes in kidney function. NGAL was proposed as a novel early marker for detection of acute renal failure. Therefore, the aim of the study was to assess whether NGAL and cystatin C predicted outcomes among 41 consecutive patients undergoing kidney transplantation. Serum NGAL and cystatin C were evaluated before, as well as 1, 3, 6, and 10 days after kidney transplantation using commercially available kits. Serum creatinine was assessed at each time. We observed a significant fall in serum NGAL as early as 1 day following kidney transplantation. Serum cystatin C decreased significantly 3 days after transplantation. Before transplantation, serum NGAL was related to creatinine and cystatin C. At each time point, serum NGAL was related positively to serum creatinine, cystatin C, and negatively to urine volume. In patients with delayed graft function, there was no fall in serum NGAL or cystatin C. Our findings may have important implications for the clinical management of patients undergoing kidney transplantation. The "window of opportunity" to distinguish between acute rejection and calcineurin inhibitor nephrotoxicity is narrow in delayed graft function. Time is limited to introduce proper treatment after the initiating insult. Therefore, NGAL needs to be investigated as a potential early marker for delayed graft function, especially in the settings of early dialysis treatment or antirejection therapy.
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PMID:Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study. 1924 1

Alzheimer's disease (AD) is characterized by accumulation and deposition of Abeta peptides in the brain. Abeta deposition in cerebrovessels occurs in many AD patients and results in cerebral amyloid angiopathy (AD/CAA). Since Abeta can be transported across blood-brain barrier (BBB), aberrant Abeta trafficking across BBB may contribute to Abeta accumulation in the brain and CAA development. Expression analyses of 273 BBB-related genes performed in this study showed that the drug transporter, ABCG2, was significantly upregulated in the brains of AD/CAA compared with age-matched controls. Increased ABCG2 expression was confirmed by Q-PCR, Western blot, and immunohistochemistry. Abcg2 was also increased in mouse AD models, Tg-SwDI and 3XTg. Abeta alone or in combination with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial cells; however, conditioned media from Abeta-activated microglia strongly induced ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and coimmunoprecipitated with Abeta. Overexpression of hABCG2 reduced drug uptake in cells; however, interaction of Abeta(1-40) with ABCG2 impaired ABCG2-mediated drug efflux. The role of Abcg2 in Abeta transport at the BBB was investigated in Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled Abeta(1-40) or scrambled Abeta(40-1). Optical imaging analyses of live animals and their brains showed that Abcg2-null mice accumulated significantly more Abeta in their brains than wild-type mice. The finding was confirmed by immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at the BBB to prevent blood Abeta from entering into brain. ABCG2 upregulation may serve as a biomarker of CAA vascular pathology in AD patients.
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PMID:ABCG2 is upregulated in Alzheimer's brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Abeta(1-40) peptides. 1940 14

Oxidative stress has been considered as one of the possible mechanisms of ischemia/ reperfusion (I/R) injury in the kidney. The aim of this study was to analyze the possible protective effect of dietary ginger (Zingiber officinals Rosc), a free radical scavenger, on renal I/R injury in rats. The protective effect of ginger against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Thirty rats were randomly divided into five experimental groups (i.e., control, sham-operated, ginger, I/R, and I/R + ginger groups, n = 6 each). The ginger and I/R + ginger groups were fed on the test diet containing 5% ginger. The rats were subjected to bilateral renal ischemia followed by reperfusion in I/R and I/R + ginger groups. At the end of the reperfusion period, rats were sacrificed, and kidney function tests, serum and tissue oxidants and antioxidants, and renal morphology were evaluated. Serum urea, creatinine, and cystatin C (CYC) levels were significantly elevated in the ischemia group, but these levels remained unchanged in the ginger + I/R group compared to the I/R group. Reduction of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activity was significantly improved by the treatment with ginger compared to I/R group. Administration of ginger resulted in significant reduction levels of tissue malondialdehyde (MDA), NO, protein carbonyl contents (PCC) in the ginger + I/R group compared with the I/R group. Ginger supplementation in the diet before I/R injury resulted in higher total antioxidant capacity (TAC) and lower total oxidant status (TOS) levels than I/R group. The ginger supplemented diet prior to I/R process demonstrated marked reduction of the histological features of renal injury. The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
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PMID:The effect of dietary ginger (Zingiber officinals Rosc) on renal ischemia/reperfusion injury in rat kidneys. 1946 72

Ischaemia/reperfusion induces systemic inflammation and oxidative stress and thereby remote organ injury in the kidney. In a double-blind, placebo-controlled clinical trial of 30 patients undergoing knee arthroplasty with tourniquet, this study evaluated the effect of N-acetylcysteine (NAC) infusion on renal function by measuring urine alpha-1-microglobulin, N-acetyl-beta-D-glucosaminidase (NAG), glutathione-S-transferase-alpha and -phi and serum creatinine and cystatin C concentrations up to 24 h post-operatively. Compared to the baseline, urine alpha-1-microglobulin/creatinine increased in both groups and was higher in the NAC group than in the placebo group at tourniquet deflation and at 3 h thereafter. Urine NAG/creatinine increased at deflation and at 3 h thereafter in the NAC group and the ratio was higher than in the placebo group. The two sensitive indicators of proximal tubular damage and function used in the present study suggest that use of NAC in clinical setting of ischaemia/reperfusion injury may increase the risk of remote kidney injury.
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PMID:Potentially detrimental effects of N-acetylcysteine on renal function in knee arthroplasty. 1952 94


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