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)

In rabbits and rats, both stimulation of alpha-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. Activation of alpha1b-adrenoceptors play an important role in the PC effect on ventricular function in rats. However, the alpha1-adrenoceptors have not been reported to be related to the PC effect in rabbits, because the infarct size-reducing effect of PC is not blocked by the nonselective alpha-adrenoceptor antagonist, phenoxybenzamine (POB) or by the alpha1-adrenoceptor antagonist, BE2254. However, we speculated that alpha1b-adrenoceptors but not alpha1a-adrenoceptors may be related to the infarct size-reducing effect of PC in rabbit hearts. Thus we examined in rabbits whether the alpha1b-adrenoceptor blocker chloroethylclonidine (CEC), the alpha1a-adrenoceptor blocker 5-methylurapidil (5-MU), the selective alpha1-adrenoceptor antagonist bunazosin (BN), and the nonselective apha-adrenoceptor antagonist phenoxybenzamine (POB) can block the PC effect on infarct size. Eighty-eight anesthetized open-chest Japanese white male rabbits were subjected to 30-min coronary occlusion and 48-h reperfusion. In five PC groups, the rabbits were subjected to a single 5-min occlusion and 5-min reperfusion before 30-min sustained ischemia. In the PC groups, those with CEC (3 mg/kg, n = 10), 5-MU (3 mg/kg, n = 10), BN (0.3 mg/kg, n = 10), POB (4 mg/kg, n = 10), or placebo saline (n = 10) were pretreated before PC. In the non-PC groups, those with CEC (3 mg/kg, n = 7), 5-MU (3 mg/kg, n = 7), BN (0.3 mg/kg, n = 7), POB (4 mg/kg, n = 7), or placebo saline (n = 10) were pretreated before 30-min sustained ischemia. After a 48-h reperfusion, the infarct size was measured histologically and expressed as a percentage of the area at risk. PC caused a marked reduction of infarct size as compared with the non-PC control (10 +/- 3% vs. 42 +/- 2%; p < 0.05). The PC effect was completely blocked by CEC (36 +/- 2%) and by BN (42 +/- 4%) but not by 5-MU (14 +/- 1%) or POB (13 +/- 2%). None of the drugs by itself affected the infarct size. Stimulation of alpha1b-adrenoceptors but not of alpha1a-adrenoceptors during PC plays an important role in the PC effect on infarct size. This may explain the previous confusion concerning the PC blocking effect of various alpha1-blockers.
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PMID:Infarct size-reducing effect of ischemic preconditioning is related to alpha1b-adrenoceptors but not to alpha1a-adrenoceptors in rabbits. 933 2

Osteochondrosis is a disorder of epiphyseal cartilage about which there is considerable confusion in the literature. We believe that this is due to the fact that osteochondrosis has been studied in the chronic stage when the lesions are morphologically complicated and the initial causative insult is impossible to determine. The etiology of osteochondrosis appears to be multifactorial, with trauma, hereditary factors and rapid growth, nutritional factors, and ischemia all having a role in its pathogenesis. Although predilection sites are variable among species, the morphology of the early lesions is strikingly similar, strongly suggesting that the pathogenesis of osteochondrosis is the same, regardless of the species affected. Based on recent studies in pigs and horses, and supported by observations in dogs and cattle, we believe that local ischemia secondary to defects in cartilage canal blood supply is a key factor in the initiation of lesions of osteochondrosis and explains many of the features of this disease. Local ischemia to the epiphyseal cartilage of the articular-epiphyseal cartilage complex leads to the formation of highly vulnerable zones of necrotic epiphyseal cartilage which later cause a delay in endochondral ossification, with extension of necrotic cartilage into the subchondral bone. Trauma, whether major or minor, to the overlying articular cartilage leads to cartilage cleft formation, clinical signs of pain and lameness, and other chronic sequelae. Studies aimed at further elucidating the pathogenesis of osteochondrosis should attempt to determine the cause of the vascular defect and whether or not it may be modified by experimental manipulations.
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PMID:The pathophysiology of osteochondrosis. 946 56

Enormous interest in cell death in the past several years has moved apoptosis to the forefront of scientific research. Apoptosis has been found to mediate cell deletion in tissue homeostasis, embryological development, and immunological functioning. It also occurs in pathological conditions, including cancer and acquired immunodeficiency syndrome, and is implicated in neurodegenerative diseases. Claims of neuronal apoptosis induced by various agents and conditions are published regularly, but in many instances the data are questionable because they are incomplete. This review presents a brief history of apoptosis and describes the evidence required before claims of apoptosis are made. Summaries and critiques of important investigations concerning the genetic and biochemical regulation of neuronal apoptosis are presented, as are other studies describing connections between apoptosis and neuronal cell death in physiological and pathological situations. There is a realization that apoptosis can be programmed and is distinguishable from necrotic cell death. Combining apoptosis with programmed cell death produces misleading terminology and confusion over these two forms of cell degeneration. Further investigations into neuronal apoptosis should focus on all of the criteria that the original investigators outlined 25 years ago, to clarify whether apoptosis and/or another form of cell death mediates neuronal degeneration in physiological settings and in neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and ischemia/stroke.
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PMID:Apoptosis in neurological disease. 952 91

A 69-year-old female presented with sudden onset of truncal ataxia, urinary incontinence, mental confusion, and Parinaud's sign. With conservative treatment, her ataxia and urinary incontinence resolved. Magnetic resonance (MR) imaging disclosed a round mass with laminated intramural hemorrhage in the third ventricle. Right vertebral angiography demonstrated a giant aneurysm in the distal basilar artery. Xenon-enhanced computed tomography showed that cerebral blood flow (CBF) was reduced in the thalamus bilaterally and was paradoxically decreased by acetazolamide. Two months later, MR imaging showed that the intramural hemorrhage had shrunk, and the edema in the thalamus was resolving. The CBF reduction and vascular response to acetazolamide had reversed to some extent. A partially thrombosed giant aneurysm can grow acutely as the result of fresh intramural hemorrhage. The edema is secondary to ischemia and loss of vasoresponsivity.
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PMID:Extensive edema in the thalamus caused by thrombosed basilar artery aneurysm. 964 Sep 62

Although hypercalcemia may cause drowsiness, lethargy, weakness, confusion and coma it rarely causes seizures or cerebral infarction. The patient presented had a clinical evolution from hallucinosis to a generalized tonic-clonic seizure, and subsequent cortical blindness with occipital cerebral ischemia as evidenced by SPECT and MRI scans. EEG revealed occipital PLEDs. With reversal of hypercalcemia, there was a return of vision, resolution of EEG epileptiform activity, although with some residual occipital infarction. This case, in concert with a literature review of hypercalcemia, reveals examples of occipital and watershed ischemia, blindness, seizures and hypertension, a pattern markedly similar to that of eclampsia. Furthermore, medications such as magnesium sulfate, believed to reverse cerebrovasospasm responsible for the eclamptic neurologic findings, may counter the effects of hypercalcemia at a cellular level, lending support to a calcium-mediated injury in eclampsia.
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PMID:Reversible hypercalcemic cerebral vasoconstriction with seizures and blindness: a paradigm for eclampsia? 966 11

Much confusion has arisen recently over the question of whether excitotoxic neuronal degeneration can be considered an apoptotic phenomenon. Here, we addressed this question by using ultrastructural methods and DNA fragmentation analysis to compare a prototypic apoptotic in vivo central nervous system cell death process (physiologic cell death in the developing rat brain) with several central nervous system cell death processes in the in vivo infant rat brain that are generally considered excitotoxic (degeneration of hypothalamic neurons after subcutaneous administration of glutamate and acute neurodegeneration induced by hypoxia/ischemia or by concussive head trauma). We found by ultrastructural analysis that glutamate induces neurodegenerative changes in the hypothalamus that are identical to acute changes induced in the infant rat brain by either hypoxia/ischemia or head trauma, and that these changes are fundamentally different both in type and sequence from those associated with physiologic cell death (apoptosis). In addition, we show by ultrastructural analysis that concussive head trauma induces both excitotoxic and apoptotic neurodegeneration, the excitotoxic degeneration being very acute and localized to the impact site, and the apoptotic degeneration being delayed and occurring in regions distant from the impact site. Thus, in the head trauma model, excitotoxic and apoptotic degeneration can be distinguished not only by ultrastructural criteria but by their temporal and spatial patterns of expression. Whereas ultrastructural analysis provided an unambiguous means of distinguishing between excitotoxic and apoptotic neurodegeneration in each example analysed in this study, DNA fragmentation analysis (TUNEL staining or gel electrophoresis) was of no value because these tests were positive for both processes.
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PMID:Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain. 1034 Apr 98

The purpose of this review is to discuss ATF3, a member of the ATF/CREB family of transcription factors, and its roles in stress responses. In the introduction, we briefly describe the ATF/CREB family, which contains more than 10 proteins with the basic region-leucine zipper (bZip) DNA binding domain. We summarize their DNA binding and heterodimer formation with other bZip proteins, and discuss the nomenclature of these proteins. Over the years, identical or homologous cDNA clones have been isolated by different laboratories and given different names. We group these proteins into subgroups according to their amino acid similarity; we also list the alternative names for each member, and clarify some potential confusion in the nomenclature of this family of proteins. We then focus on ATF3 and its potential roles in stress responses. We review the evidence that the mRNA level of ATF3 greatly increases when the cells are exposed to stress signals. In animal experiments, the signals include ischemia, ischemia coupled with reperfusion, wounding, axotomy, toxicity, and seizure; in cultured cells, the signals include serum factors, cytokines, genotoxic agents, cell death-inducing agents, and the adenoviral protein E1A. Despite the overwhelming evidence for its induction by stress signals, not much else is known about ATF3. Preliminary results suggest that the JNK/SAPK pathway is involved in the induction of ATF3 by stress signals; in addition, IL-6 and p53 have been demonstrated to be required for the induction of ATF3 under certain conditions. The consequences of inducing ATF3 during stress responses are not clear. Transient transfection and in vitro transcription assays indicate that ATF3 represses transcription as a homodimer; however, ATF3 can activate transcription when coexpressed with its heterodimeric partners or other proteins. Therefore, it is possible that, when induced during stress responses, ATF3 activates some target genes but represses others, depending on the promoter context and cellular context. Even less is understood about the physiological significance of inducing ATF3. We will discuss our preliminary results and some reports by other investigators in this regard.
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PMID:ATF3 and stress responses. 1044 Feb 33

The free radical nitric oxide (NO) has emerged in recent years as a fundamental signaling molecule for the maintenance of homeostasis, as well as a potent cytotoxic effector involved in the pathogenesis of a wide range of human diseases. Although this paradoxical fate has generated confusion, separating the biological actions of NO on the basis of its physiologic chemistry provides a conceptual framework which helps to distinguish between the beneficial and toxic consequences of NO, and to envision potential therapeutic strategies for the future. Under normal conditions, NO produced in low concentration acts as a messenger and cytoprotective (antioxidant) factor, via direct interactions with transition metals and other free radicals. Alternatively, when the circumstances allow the formation of substantial amounts of NO and modify the cellular microenvironment (formation of the superoxide radical), the chemistry of NO will turn into indirect effects consecutive to the formation of dinitrogen trioxide and peroxynitrite. These "reactive nitrogen species" will, in turn, mediate both oxidative and nitrosative stresses, which form the basis of the cytotoxicity generally attributed to NO, relevant to the pathophysiology of inflammation, circulatory shock, and ischemia-reperfusion injury.
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PMID:Biology of nitric oxide signaling. 1080 15

Several clinical studies promulgate the concept that some degree of crossover innervation occurs after digital nerve injuries are sustained and that the intact digital nerve might even substitute for the loss of nerve function on the injured side. Other studies strongly dispute the existence of this phenomenon. An excellent model for evaluation of crossover innervation is bilateral sharp digital nerve lacerations because there is no confusion of anomalous innervation from an intact contralateral nerve. This model avoids problems seen with replanted digits such as the inherent ischemia, multistructural injury, and the frequent crush component. The author evaluates the role of crossover innervation after digital nerve injury by comparing recovery of sensibility after unilateral and bilateral epineural neurorrhaphies. A retrospective review of 74 sharp unilateral and bilateral epineural digital nerve repairs in 54 patients using microsurgical techniques was performed by measurement of Weber's two-point discrimination (2PD). Fifty-four unilateral digital nerve repairs were performed in 46 patients who ranged in age from 8 to 54 years (mean age, 30.8 years). Concomitant flexor tendon injuries occurred in 50% of patients. Injury to repair was less than 1 day in 14.3% of patients, 2 to 7 days in 34.7%, 8 to 30 days in 40.8%, and 31 to 300 days in 10.2%. Follow-up ranged from 6 to 68 months (average follow-up, 13.8 months). Twenty bilateral digital nerve repairs were performed in 8 patients who ranged in age from 6 to 37 years (mean age, 27.6 years). Concomitant flexor tendon injuries occurred in 80% of patients. Injury to repair was less than 1 day in 10% of patients, 2 to 7 days in 60%, 8 to 30 days in 20%, and 31 to 300 days in 10%. Follow-up ranged from 6 to 77 months (average follow-up, 15.8 months). In this series, 2PD averaged 7.8 mm after unilateral digital nerve repairs compared with 7.1 mm after bilateral nerve repairs. Recovery of sensibility was also stratified into groups according to modified American Society for Surgery of the Hand guidelines: excellent, <6 mm; good, 6 to 10 mm; fair, 11 to 15 mm; and poor, >15 mm or protective sensation. Unilateral digital nerve repairs produced excellent results in 27.8% of patients, good in 46.3%, and fair in 25.9% compared with bilateral nerve repairs with excellent results in 15% of patients, good in 70%, and fair in 15%. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Crossover innervation did not appear to influence the long-term outcome after digital neurorrhaphy.
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PMID:Crossover innervation after digital nerve injury: myth or reality? 1109 60

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.
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PMID:Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. 1176 65


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