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

A model is proposed for the role of the kidney in the control of erythropoietin production in which the initial trigger is an oxygen deficit created by anemia, hypobaria or ischemia. It is postulated that hypoxia creates a decrease in the oxygen level in a critical renal sensor cell, perhaps in the glomerular tuft, which eventually leads to the production of prostacyclin. It is possible that the endothelial cell in the glomerular tuft responds to this oxygen deficit to produce prostacyclin to trigger erythropoietin production. Recent studies on prostaglandin synthesis by human isolated glomeruli indicate that the most abundant prostanoid synthesized by the glomerular tuft cells was 6-keto PGF1 alpha, a metabolite of prostacyclin (PGI2). PGI2 has also been reported to be produced by isolated vascular endothelial cells. The mechanism by which hypoxia may initiate the synthesis and/or release of prostaglandins and prostacyclin in the renal cell has not been elucidated. Significant to erythropoietin production is the production by hypoxia of prostacyclin which eventually leads to the production of the metabolite 6-keto PGE1. We further propose that 6-keto PGE1 is the prostanoid which activates a specific cell membrane adenylate cyclase, causing the conversion of ATP to cyclic AMP. This is a very critical step in that there must be a sufficient amount of ATP remaining to generate cyclic AMP in order for erythropoietin biosynthesis to occur with the reduced level of ATP which may have caused a perturbation of the cell membrane. The elevated cyclic AMP leads to the activation of protein kinases which are essential in phosphorylating the lysosomal hydrolases released by hypoxia into the cytosol of the cell and may be the precursors of erythropoietin. Neutral proteases and lysosomal hydrolases, documented triggers of erythropoietin production, have been demonstrated to be elevated in the kidney after hypoxia. The mechanism of labilization and release of these enzymes from the renal lysosomes has been postulated to be related to increases in cyclic GMP levels in a renal cell. Hypoxia causes the release of renal lysosomal hydrolases which then undergo phosphorylation through activation by protein kinases following prostanoid stimulation of renal adenylate cyclase to generate cyclic AMP, resulting in increased biosynthesis of erythropoietin.
 ...
PMID:Prostanoid activation of erythropoiesis. 654 29

Male weanling rats were made copper deficient with a purified diet containing all known essential dietary nutrients except copper. Copper deficiency was verified by indirect (anemia, growth retardation, hypercholesterolemia, gross pathology, and abnormal electrocardiograms) and direct (tissue copper analysis) criteria. His bundle electrographic and electrocardiographic changes detected in the copper-deficient group consisted most notably of depressed His-Purkinje system conductivity and S-T segment depression. Phosphorus-31 nuclear magnetic resonance spectroscopic analysis of cardiac, renal, and hepatic tissue perchloric acid extracts revealed significant metabolic changes associated with the dietary copper deficiency, including a generalized marked decrease in ATP and phosphocreatine levels and a corresponding increase in inorganic orthophosphate and ADP levels in the various tissues. Tissue-specific changes consisting of elevated ribose 5-phosphate (heart), phosphocholine (heart), and inosine monophosphate (kidney) and decreased glycerol 3-phosphorylethanolamine (liver) and glycerol 3-phosphorylcholine (liver) levels were detected in copper-deficient rats. Microscopic examination of heart tissue from copper-deficient rats revealed extensive disruption of mitochondrial fine structure, including fragmentation of cristae and inner and outer mitochondrial membranes, which resulted in pronounced vacuolization throughout the tissue. Although the physiological and metabolic disturbances manifested in hearts from copper-deficient animals generally mimic myocardial responses to chronic ischemia, the observed changes are interpreted in a broader context to represent the appearance of a copper-dependent cardiomyopathy.
 ...
PMID:Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. 663 5

An 11 year old boy was admitted to the Department of Pediatrics Medical School of Vienna with 2nd and 3rd degree burns covering 30% of his body. He presented with complications--high fever, vomiting, diarrhea and dehydration--which had led to acute renal failure. After 6 hemodialyses renal function recovered after two weeks and the patient entered a polyuric phase. In connection with a transient dehydration the patient showed a sudden bilateral cortical blindness. The computerized tomogram (CT) showed vague evidence of an occipital cortical ischemia. We assume that several factors have played a role in this sudden occurrence. As a result of hypovolemia and coincident anemia and electrolyte inbalance, cerebral edema and cortical tissue hypoxia with emphasis in the occipital cortical region developed in the brain possibly already damaged by burn injury. A complete reversal of the clinical state was achieved. The patient was discharged with normal vision and normalized renal function.
 ...
PMID:[Acute cortical blindness: a reversible complication of acute kidney failure in a child with burns]. 683 79

Giant-cell arteritis is a polysymptomatic disease of the elderly. Systemic symptomatology includes headaches, arthralgias, myalgias, tender temporal arteries, jaw claudication, low-grade fever, anemia, anorexia, malaise, and weight loss. Visual loss from anterior ischemic optic neuropathy and diplopia resulting from ischemia of the ocular muscles represents the major ocular manifestations of giant cell arteritis. When the diagnosis is suspected, blood for a sedimentation rate should be drawn, and, if it confirms the clinical impression, high dose prednisone should be started immediately and a temporal artery biopsy performed at a later date. Only by asking the proper questions and suspecting the diagnosis will this preventable form of blindness receive the prompt attention it deserves.
 ...
PMID:Giant-cell arteritis. Signs and symptoms. 715 21

Both experimental traumatic brain injury and clinical traumatic brain injury appear to render the brain more vulnerable to a second ischemic insult. The mechanisms of enhanced vulnerability to subsequent ischemia appear to include a reduced ability to increase cerebral blood flow in response to hypotension, hypoxemia, or acute anemia and increased tissue sensitivity to ischemia. Although numerous mediators may be involved in increased tissue sensitivity, those that particularly merit investigation include oxygen free radicals, glutamate, arachidonate metabolites, calcium ions, and protein kinase C.
 ...
PMID:Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury. 749 45

Anemia does not correct in many kidney transplant recipients, probably due to iron deficiency or inadequate erythropoietin (Epo) production. We evaluated effects of iron (Fe) availability on correction of anemia in renal transplant recipients and sought to characterize patterns of early Epo production by transplanted kidneys as related to peritransplant factors. In a prospective randomized trial, 51 consecutive renal transplant patients were followed for 6 months. Epo was measured on days 0, 3, 14, 48 and 168 posttransplantation. Fe status was monitored on days 14, 48 and 168. Pts were randomized at day 14 based on Fe status. Iron-deficient (FeD) patients (n = 24) were randomized to receive daily Fe supplementation (FeDs, n = 12) or no supplementation (FeDns, n = 12). Those with normal Fe status (FeN, n = 27) were followed as controls. No differences were found between groups at day 0 for Hct, Cr, Epo, age, dialysis history, or type of donor. Day 3 Creatinine and Hct were similar among groups, while Epo was significantly higher in FeD groups vs FeN (p < 0.004), and continued higher at 6 months. Though each pt improved Hct, most FeDns and FeN were anemic and Fe deficient at 6 months while all FeDs patients had corrected their anemia (p < or = 0.009) and Fe status. Four FeDs patients developed polycythemia. Epo production correlated inversely to cold ischemia time in cadaver renal allografts (p < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Factors affecting erythropoietin production and correction of anemia in kidney transplant recipients. 794 39

Male Sprague-Dawley rats aged 3 weeks that were maintained on an iron-deficient diet for 4-5 weeks developed severe anemia with markedly reduced hemoglobin levels (3.94 +/- 0.14 Hb g% versus controls 12.9 +/- 0.11 Hb g%). Iron-deficiency resulted in marked cardiac hypertrophy (cardiomegaly). On sacrifice, the hearts were processed for light and transmission electron microscopy. The major ultrastructural changes were found in the hypertrophied left ventricle and left papillary muscles. Iron-deficiency caused marked edema in myocytes, sarcomeres were out of register, and degeneration and discontinuities in myofilaments were common. Iron-deficiency resulted in the enlargement of the interfibrillar mitochondria, changes in the matrix and the formation of electron-dense amorphous bodies. The ultrastructural changes in myocytes in response to experimental iron-deficiency were similar to those described by others in cases of experimental ischemia or hypoxia. Mitochondrial changes were also found in the atria of iron-deficient rats. Quantitative cytochemical measurement of succinate dehydrogenase activity was determined and was shown to be substantially reduced in the iron-deficient heart. In severely iron-deficient rats restored to a normal iron-sufficient diet for two weeks, hemoglobin levels recovered, however the myocytes of the hypertrophied left ventricles and papillary muscles continued to show severe degenerative changes.
 ...
PMID:Ultrastructural and cytochemical changes in the heart of iron-deficient rats. 820 92

GI bleeding occurs with prolonged exercise and is probably mediated by visceral ischemia. It may produce acute hemorrhage, more chronic symptoms with anemia, or result in guaiac-positive conversion with little clinical disease. Hemorrhagic gastritis and colitis are the most frequently recognized lesions, and are usually transient and reversible. Acid suppression with cimetidine may be effective in selected patients with recurrent HG, but effective therapy for most patients with this form of GI bleeding is still uncertain. Awareness of the association between GI bleeding and exercise should stimulate further investigations into the pathophysiology and therapy.
 ...
PMID:Gastrointestinal bleeding and the athlete. 830 30

The present knowledge on periventricular leucomalacia is reviewed. Its incidence is about 10% in preterms infants < 32 gestational weeks. By careful ultrasonographic scanning four stages can be distinguished: Prolonged flares, resolution, cystic leucomalacia, ventriculomegaly. Periventricular leucomalacia (PVL) is much more correlated with later neurologic impairment than intraventricular haemorrhage (apart from grade IV). PVL is caused by ischemia of the periventricular white matter mainly due to arterial hypotension and disturbed regulation of cerebral blood flow. The interactions between blood pressure, pCO2, pO2 and cerebral blood flow are complex and poorly understood. Regarding the clinical management it seems important to avoid hypotension, fluctuating pCO2 and hypoxemia/anemia in order to prevent white matter ischemia. Research should be focussed on the development of monitoring methods (doppler sonography, near infrared spectroscopy, time compressed electroencephalography), which allow to detect ischemic events to prevent neurologic impairment in about 1000 preterm infants per year in Germany.
 ...
PMID:[Periventricular leukomalacia]. 841 33

This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle. 844 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>