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)

17 parameters of vital activity (VA) were scanned in 35 female and 12 male dependent geriatric patients (mean age 81). These included mental testing, Barthel score, lung function, urinanalysis, creatinine clearance, Hb, albumin, globulin and electrolytes, skin-folds, locomotion, presence of IHD, hemodynamic state, continence, infections, WBC and lymphocyte count, pressure sores and dysphagia, 4 main templates of VA deterioration identified were: IHD, hemisyndrome (due to CVA), vegetative state (post-CVA) and senile dementia (SDAT). The IHD template was characterized by marked variations in VA, ending in death due to cardiac complications (pulmonary edema, ischemia, etc.). In the 3 other templates VA gradually deteriorated. Gradual declining VA allowed assessment of individual mortality prognosis. Assessment was by approximation of the computed exponent of the extrapolated VA curves; the longer the observation, the fewer the mistakes in assessment. Epidemiologic prognosis data of 48 dependent patients is described; mean age was about 81 years. Hospitalization mean was 853.5 +/- 601 days and for patients with dementia, 1158.6 +/- 622.7 days.
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PMID:[Assessment of vital activity in geriatric patients]. 781 43

The recent molecular cloning of BDNF and CNTF based on traditional protein purification and protein sequencing and the identification and cloning of NT-3 and NT-4 by homology cloning strategies has led to a tremendous flurry of interest in the biology of these proteins and initiation of studies to assess their potential utility in neurological disorders ranging through degenerative disease, stroke and ischemia, trauma and peripheral neuropathies. Tissue culture studies have been very useful in identifying neuronal specificities of the neurotrophins and CNTF and in combination with localization studies of these growth factors and their receptors have provided the basis for in vivo studies. Initial animal studies with BDNF indicate efficacy of BDNF in models of Alzheimer's and Parkinson's disease and small fiber sensory neuropathy. Studies with CNTF have similarly progressed from in vitro findings, especially the discovery that CNTF is a growth factor for motor neurons, to in vivo findings where CNTF has been shown to be effective in slowing symptoms of motor neuron dysfunction in three genetic models. Based on these positive animal data, CNTF is currently in clinical trials for the potential treatment of motor neuron disease or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
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PMID:Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor. 783 3

CDP-choline, supplied exogenously as citicoline, has beneficial physiological actions on cellular function that have been extensively studied and characterized in numerous model systems. As the product of the rate-limiting step in the synthesis of phosphatidylcholine from choline, CDP-choline and its hydrolysis products (cytidine and choline) play important roles in generation of phospholipids involved in membrane formation and repair. They also contribute to such critical metabolic functions as formation of nucleic acids, proteins, and acetylcholine. Orally-administered citicoline is hydrolyzed in the intestine, absorbed rapidly as choline and cytidine, resynthesized in liver and other tissues, and subsequently mobilized in CDP-choline synthetic pathways. Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid degradation. Exogenously administered citicoline prevents, reduces, or reverses effects of ischemia and/or hypoxia in most animal and cellular models studied, and acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Thus, considerable accumulated evidence supports use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in conditions such as ischemic and traumatic injuries. Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson's disease, cardiovascular disease, aging, Alzheimer's disease, learning and memory, and cholinergic stimulation.
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PMID:Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. 786 46

The pharmacological inhibition of excitatory amino acid neurotransmission has evolved to be a major topic in neuropharmacology since enhanced synaptic action of glutamate and possibly other related neurotransmitters has been suggested to play a role both in acute neurological conditions such as ischemia and epilepsy and in chronic degenerative neurological diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. While antagonists at N-methyl-D-aspartate (NMDA) type glutamate receptors include psychotomimetic and neurotoxic agents such as phencyclidine and MK-801, the aminoadamantanes represent a class of drugs which may be largely free of such actions and which have already been used clinically as antiviral and antiparkinsonian agents. Multiple in vitro studies have recently delineated the neuroprotective properties of amantadine, and of its more potent congener, memantine, which appear to mediate neuroprotection via inhibition of NMDA receptor-dependent glutamate activity. Thus, neuroprotection targeting glutamate receptors does apparently not have to be associated with prominent psychotogenicity, and the development and evaluation of new neuroprotective drugs will have to performed in consideration both of the relative safety and of the good clinical effect of the already known and established aminoadamantanes.
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PMID:Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. 788 11

Although found as a precursor of Alzheimer amyloid, substantial evidence suggests that beta/A4 protein precursor (APP) is involved in regulation of neuronal growth and survival. Recently, we have obtained evidence that the trophic properties of APP are fully preserved in a 17-amino acid sequence. If APP is neurotrophic, then it would be anticipated that administration of the growth-promoting segment of the APP 17-mer peptide might attenuate the neuronal dysfunction or loss or behavioral deficits associated with neuronal injury, such as that accompanying central nervous system ischemia. We evaluated this 17-mer peptide in a rabbit spinal cord ischemia model and found that this peptide alleviates paraplegia resulting from ischemia/reperfusion. Ischemia of the distal lumbar cord was produced by temporary occlusion of the abdominal aorta. Saline, 17-mer APP peptide, or a control peptide (200, 500, or 1000 nM) was administered intrathecally 20 min prior to ischemia and once daily for 3 days thereafter. The neurologic and morphologic outcomes were evaluated after 4 days. Durations of ischemia encompassing all grades of neurologic function were included. The 500 nM dose of 17-mer APP peptide significantly reduced neurologic damage. The average ischemia duration necessary to produce permanent neurologic damage increased from 27.9 +/- 1.9 min in saline-injected controls and 27.7 +/- 2.0 in scrambled sequence peptide-injected controls to 40.2 +/- 4.0 min in the 500 nM 17-mer APP-injected group. The 200 nM dose produced a nonsignificant trend toward reduced neurologic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of neurological damage by a peptide segment of the amyloid beta/A4 protein precursor in a rabbit spinal cord ischemia model. 792 33

Heat shock proteins (HSPs) are a highly conserved group of proteins which are produced when cells are confronted with a variety of stressful insults such as heat shock, hypoxia/ischemia, metabolic disruption, and exposure to cytotoxic reagents. Under unstressed conditions, HSPs act as molecular chaperones which play pivotal roles in the course of maturation of various cellular proteins. Under stressed conditions, they play a protective role against irreversible cell damage and promote recovery of the cells experiencing stress. In the central nervous system, proteins of the HSP 90, HSP 70, HSP 60, and small HSP families are expressed constitutively and/or induced by stressful events, differentially in distinct cell types. Aberrant expression of HSPs might be implicated in the pathogenesis of neurological disorders such as multiple sclerosis and Alzheimer's disease.
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PMID:[Heat shock proteins and neurological disorders]. 799 81

Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Normal excitation of glutamate receptors initiates the stimulation of phospholipases and lipases with the generation of second messengers that are necessary for normal cell function. The overstimulation of glutamate receptors can initiate a cascade of biochemical events including stimulation of membrane phospholipid turnover, excessive calcium entry, abnormal phosphorylation, and proteolysis. These events may be responsible for neuronal injury and degeneration found in Alzheimer disease, ischemia, spinal cord trauma, epilepsy, and Huntington disease.
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PMID:Involvement of glutamate receptors, lipases, and phospholipases in long-term potentiation and neurodegeneration. 805 91

Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.
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PMID:Cerebral ischemia induces alterations in tau and ubiquitin proteins. 808 73

Cytokines were first characterized as high-molecular weight modulators of the immune response. However they also play an important role in the CNS. Thus, some cytokines could influence the synaptic transmission or modulate the neuronal and glial growth during brain development or after brain injury. Activated glial cells appear to be the major cytokines producing cells. Some of these cytokines are glial cells mitogens, whilst others have a direct neurotrophic activity. These effects seem to be mediated by receptors similar to those of neurotrophic factors. Cytokines might be crucial factors in the evolution of different acute or chronic neuropathological processes such as ischemia, brain trauma, multiple sclerosis and Alzheimer's disease. Control of their effect on brain cells could allow prevention of brain damage observed in such pathologies.
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PMID:[Role of cytokines in the central nervous system]. 809 43

This review summarizes emerging evidence that supports the notion of a separate brain renin-angiotensin system (RAS) complete with the necessary precursors and enzymes for the formation and degradation of biologically active forms of angiotensins, and several binding subtypes that may mediate their diverse functions. Of these subtypes the most is known about the AT1 site which preferentially binds angiotensin II (AII) and angiotensin III (AIII). The AT1 site appears to mediate the classic angiotensin responses concerned with body water balance and the maintenance of blood pressure. Less is known about the AT2 site which also binds AII and AIII and may play a role in vascular growth. Recently, an AT3 site was discovered in cultured neoblastoma cells, and an AT4 site which preferentially binds AII(3-8), a fragment of AII now referred to as angiotensin IV (AIV). The AT4 site has been implicated in memory acquisition and retrieval, and the regulation of blood flow. In addition to the more well-studied functions of the brain RAS, we review additional less well investigated responses including regulation of cellular function, the modulation of sensory and motor systems, long term potentiation, and stress related mechanisms. Although the receptor subtypes responsible for mediating these physiologies and behaviors have not been definitively identified research efforts are ongoing. We also suggest potential contributions by the RAS to clinically relevant syndromes such as dysfunctions in the regulation of blood flow and ischemia, changes in cognitive affect and memory in clinical depressed and Alzheimer's patients, and angiotensin's contribution to alcohol consumption.
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PMID:Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. 817 Jun 22


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