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)

Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases.
 ...
PMID:Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair. 864 60

Vascular dementia (VD) and Alzheimer's type dementia are two main causes of dementia in the aged. Considering historical backgrounds and ethnic differences, a simplified classification of VD is suggested. First, poststroke dementia of acute onset associated with an infarct that is large enough to impair general cognitive functions, or strategically located. Second, multi-infarct dementia that develops incrementally with increasing numbers of infarcts, and which should be classified as multiple cortical infarct dementia and multiple small infarctor lacunar dementia. Third, vascular dementia of the Binswanger type (VDBT). We compared two types of white matter lesions, periventricular hyperintensity (PVH) and confluent centrum semiovale hyperintensity (CCSH) in lacunar stroke patients with regard to the cerebral blood flow (CBF). In patients with PVH, there was a significant positive correlation between the dementia scores and the CBF in the parietal and temporal areas but not in the frontal area. In CCSH patients, there was a significant positive correlation in the frontal area but not in the parieto-temporal areas. Therefore, dementia in most patients with PVH may not be primarily related to the PVH, but may possibly be due to coexisting Alzheimer's type dementia, and dementia in most CCSH patients may be related to cerebrovascular disease. VDBT is unique clinically in its slowly progressive intellectual deterioration and pathologically in diffuse, confluent, and almost symmetrical white matter lesions. For the pathogenesis of VDBT, our studies suggest that hypertension, short-term variations in blood pressure, and a sustained nighttime elevation of blood pressure promote small vessel disease and cause ischemia of the cerebral white matter that is located in the end-fields of penetrating arteries; this leads to an imparied integrity of the blood-brain barrier and free radical generation, both of which may have important roles in producing diffuse white matter degeneration.
 ...
PMID:[Problems in vascular dementia]. 864 89

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects.
 ...
PMID:[Free radicals in the central nervous system]. 866 12

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
 ...
PMID:CDP-choline: pharmacological and clinical review. 870 78

Advances in computer technology provide a wide range of applications which are revolutionizing the practice of medicine. The development of new software for the office creates a web of communication among physicians, staff members, health care facilities and associated agencies. This provides the physician with the prospect of a paperless office. At the other end of the spectrum, the development of 3D work stations and software based on computational chemistry permits visualization of protein molecules involved in disease. Computer assisted molecular modeling has been used to construct working 3D models of lens alpha-crystallin. The 3D structure of alpha-crystallin is basic to our understanding of the molecular mechanisms involved in lens fiber cell maturation, stabilization of the inner nuclear region, the maintenance of lens transparency and cataractogenesis. The major component of the high molecular weight aggregates that occur during cataractogenesis is alpha-crystallin subunits. Subunits of alpha-crystallin occur in other tissues of the body. In the central nervous system accumulation of these subunits in the form of dense inclusion bodies occurs in pathological conditions such as Alzheimer's disease, Huntington's disease, multiple sclerosis and toxoplasmosis (Iwaki, Wisniewski et al., 1992), as well as neoplasms of astrocyte origin (Iwaki, Iwaki, et al., 1991). Also cardiac ischemia is associated with an increased alpha B synthesis (Chiesi, Longoni et al., 1990). On a more global level, the molecular structure of alpha-crystallin may provide information pertaining to the function of small heat shock proteins, hsp, in maintaining cell stability under the stress of disease.
 ...
PMID:Advances in computer technology: impact on the practice of medicine. 872 7

B/A4 is the major component of brain amyloid plaque, one of the hallmarks of Alzheimer's disease (AD). B/A4 is a product of proteolytic processing of its precursor, the Alzheimer amyloid precursor protein (APP). Recently, apolipoprotein E (APO-E) has also been shown to be associated with Alzheimer's disease pathology because it is localized to plaques and tangles, and the gene encoding one of the isoforms of APO-E (E4) is associated with late-onset familial and sporadic AD. In addition, APO-E exhibits high affinity for binding to the B-peptide (B/A4). In this study, we have investigated changes in the steady state levels of APP, APO-E, and the astrocyte-specific marker, glial fibrillary acidic protein (GFAP) mRNA in the gerbil hippocampal CA1 region after a 10-min period of bilateral carotid occlusion-induced forebrain ischemia. Following this insult, we observed a loss of 90% of the CA1 neurons by 72 h post-ischemia. The mRNA levels on day 1 through day 7 post-ischemia were quantitated using an image analyzer. There was an increase in the transcription of APO-E and GFAP mRNAs, with the levels of APO-E mRNA being the highest (3-fold increase on day 7 post-ischemia) (P < 0.005). However, we did not see an increase in APP mRNA. In a parallel study [Hall, E.D. et al., Exp. Neurol., 135(1995) 17-27], we have also seen an increase in levels of APO-E and GFAP protein measured by immunocytochemistry. However, in contrast to the lack of an increase in APP mRNA, immunocytochemical measurement of APP did show an increase, perhaps due to delayed translation of previously formed mRNA. We suggest that neuronal injury or insult results in the induction of certain genes (and, therefore, protein synthesis) in the surrounding reactive astrocytes, and these proteins may contribute to post-injury amyloidogenesis.
 ...
PMID:Induction of apolipoprotein E mRNA in the hippocampus of the gerbil after transient global ischemia. 873 65

White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly subjects. The purpose of this study was to characterize metabolic changes in the white matter of elderly subjects with extensive WMSH. We used water-suppressed proton (1H) magnetic resonance spectroscopic imaging (MRSI) to compare six subjects with extensive WMSH with eight age-matched elderly subjects with minimal or absent WMSH, and phosphorus (31P) MRSI to compare nine subjects with extensive WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to region-matched tissue in elderly controls, extensive WMSH were associated with increased signal from choline-containing metabolites, no significant change of signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME) resonance. These findings suggest that WMSH may be associated with an alteration of brain myclin phospholipids in the absence of axonal damage. There were no differences in energy phosphates, consistent with lack of ongoing brain ischemia. Within the group with extensive WMSH, PME resonance measures were significantly lower in WMSH than in contralateral normal-appearing white matter. These results provide information on pathophysiology of WMSH and a basis for comparison with WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other diseases.
 ...
PMID:1H and 31P magnetic resonance spectroscopic imaging of white matter signal hyperintensity areas in elderly subjects. 874 91

Dementia of the Alzheimer type, senile onset (SDAT), and multi-infarct dementia (MID) exhibit differences in cerebrovascular blood flow velocity profiles, which were investigated by means of transcranial Doppler sonography. The pulsatility indices (PI), as angle-independent parameters of peripheral vascular resistance measured in the basal cerebral arteries, were significantly increased in MID patients with respect to SDAT cases. In an analysis of the correlations between several variables and the magnitude of PI, we found strong inverse correlations of the CAMCOG score, and strong direct correlations of the blood pressure and the duration of illness, with the PI of all basal cerebral arteries only in MID patients. In SDAT patients, we found a direct correlation between the Hachinski ischemia score and the PI of all basal cerebral arteries. All 3 ischemia scores (Hachinski, Rosen, Loeb and Gandolfo) were significantly correlated with the PI of the middle cerebral and basilar arteries. By analyzing the correlations of the single items of the 3 different ischemia scores with the PI values obtained, we only found a clearcut correlation with the item focal neurological signs. Thus, our findings stress the relative importance of a concomitant cerebrovascular factor in the development of dementia in old age, even in patients with probable SDAT. A raise of the PI in the basal cerebral arteries allows early suspicion of a cerebrovascular factor even in only slight dementia so that possible risk factors for further aggravation of this type of vascular dementia might be detected and treated early in the course of disease.
 ...
PMID:Senile dementia of Alzheimer type and multi-infarct dementia investigated by transcranial Doppler sonography. 878 81

Free radicals are thought to be involved in the onset of neuronal disturbances such as Alzheimer's disease, Parkinson's disease, and neuronal ceroid lipofuscinosis. It is also assumed that they play a role in cerebral injury caused by ischemia or trauma. Plasma and cerebrospinal fluid (CSF), Total (peroxyl) Radical-trapping Antioxidant Parameter (TRAP), and the known antioxidant components of TRAP, for instance, ascorbic acid, uric acid, protein sulfhydryl groups, tocopherol, and ubiquinol were analyzed and the remaining unidentified fragment was calculated in five healthy volunteers before and after 4 weeks of ascorbate and ubiquinone (Q-10) supplementation. In CSF, TRAP was significantly lower than in plasma. The major contributor to plasma's antioxidant capacity was uric acid (UA), whereas in CSF it was ascorbic acid (AA). In CSF, AA concentrations were four times higher than in plasma. Oral supplementation of AA (500 mg/d first 2 weeks, 1,000 mg/d following 2 weeks) and Q-10 (100 mg/d first 2 weeks, 300 mg/d following 2 weeks) induced a significant increase in plasma AA and Q-10. Surprisingly, in spite of the high lipophilicity of Q-10, its concentration did not change in CSF. The supplementation of AA increased its concentration in CSF by 28% (p < .05). However, the increase in AA did not result in an increase in CSF TRAP. This indicates that AA had lost one-third of its radical trapping capacity as compared to that in plasma. The facts that AA is the highest contributor to CSF TRAP and its effect on TRAP is concentration dependent could indicate that the peroxyl radical-trapping capacity of CSF is buffered by AA.
 ...
PMID:The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. 881 36

The clinical condition known as vascular dementia remains poorly defined. Few studies have attempted a correlative link between the clinical syndrome and the structural abnormalities of the brain. Classically the clinical progression of the vascular dementing process is thought to be a multi-step process punctated by repeated episodes of ischemia, that are clinically expressed as strokes. In most instances it has been assumed that the substrate of vascular dementias consists of atherothrombotic infarcts. The objective of this report is to illustrate 3 cases of progressive (rather than stepwise) cognitive deterioration without clinical evidence of stroke, evolving over a period of several years, in which there were prominent vascular lesions. A complete autopsy and detailed neuropathologic examination demonstrated cerebral vascular lesions involving small arterial vessels (< 200 microns in diameter). The lesions consisted of moderate-to-severe arteriolosclerosis in two cases, and mild-to-moderate arteriolosclerosis in a case of Alzheimer's disease with severe cerebral amyloid angiopathy. Parenchymal lesions consisted of small cortical and subcortical infarcts, most of them smaller than 0.1 cm in average diameter, and subcortical leukoencephalopathy severe in two cases and mild-to-moderate in the third case. Severe atherosclerosis not accompanied by large infarcts was also present in one case. Arterial changes affecting small, distal branches causing sometimes small parenchymal lesions in association with diffuse cerebral white matter disease, appear to be the anatomical substrate that accompanies progressive cognitive impairment in some patients who are frequently diagnosed with Alzheimer's disease because in their clinical records there is neither history of strokes nor stepwise progression of symptoms.
 ...
PMID:Vascular pathology in three cases of progressive cognitive deterioration. 886 69


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