Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-one patients with acute brain infarction, 8 with transient ischemic attack and 20 controls were investigated for lumbar cerebrospinal fluid (CSF) monoamine metabolites and cholinesterases. The diseased patients were lumbar punctured on 2 occasions, mean Days 1 (0-3) and 5 (3-9) after debut of symptoms. Monoamine concentrations were determined by reverse phase liquid chromatography with electrochemical detection and the cholinergic enzymes were measured photometrically. Increased concentrations of 3-methoxytyramine (3-MT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HI-AA) and increased activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in lumbar cerebrospinal fluid was found in patients with acute brain infarction when compared to control values, while the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were not altered. No change of any neurotransmitter metabolite concentration/enzyme activity were found between Day 1 and Day 5 in the diseased patients. These data suggest an increased release of these neurotransmitter markers from necrotic brain areas into the cerebrospinal fluid and/or altered barriers between blood, brain and CSF and/or a dysfunction of the arachnoid villi to clear substances from the CSF. We therefore concluded that CSF neurotransmitters may be useful as specific brain markers in acute stroke.
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PMID:Increased monoamine metabolite concentrations and cholinesterase activities in cerebrospinal fluid of patients with acute stroke. 343 5

Serum Zn and Cu was investigated in 67 patients with cerebral infarction (CI), in 10 with cerebral hemorrhage (CH), in 14 with transient ischemic attack (TIA) and in 58 control subjects (C). Serum Zn concentration is significantly lower in patients with CH than in C (p < 0.001), and serum Cu is significantly higher than in C in patients with CI (p < 0.005). In patients with CI and in C serum Zn concentration decreased with advancing age. The serum Zn concentration decreased significantly in patients with CI during hospitalisation (p < 0.001), probably due to low intake and insufficient absorption. In patients with CI a significant correlation was found between low levels in serum Zn, on the one hand, and serum cholinesterase and proteinemia, on the other hand. This suggests a diminution of hepatic synthesis of proteins in these patients.
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PMID:Serum zinc and copper in patients with cerebral vascular disease. 853 48

Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degeneration and as biomarkers of the disease. To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted.
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PMID:Effects of time and cholinesterase inhibitor treatment on multiple cerebrospinal fluid parameters in Alzheimer's disease. 1059 54

There is increasing evidence to suggest that patients with vascular dementia (VaD) exhibit a cholinergic deficit. These patients may therefore benefit from treatment with cholinesterase (ChE) inhibitors such as donepezil. However, there are difficulties in accurately defining patients with VaD. Clinical trials to assess the efficacy and tolerability of donepezil in patients with VaD have been completed. National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria were used to establish inclusion and exclusion criteria: evidence of dementia (impaired memory and two other cognitive domains), and evidence of cerebrovascular disease (CVD) from neuroimaging and physical examination and a possible or probable relationship between dementia and CVD were required for enrollment. Patients with a diagnosis of Alzheimer's disease (AD) or dementia caused by other conditions not associated with the cardiovascular system (e.g., MS, chronic infections, hypothyroidism) were excluded. These criteria ensured that only patients with probable or possible VaD were enrolled. Enrolled patients had a mean Hachinski score of 9.7, with memory impairment the most prominent feature of their dementia. Sixty percent of patients had a history of at least one stroke and 18% of patients had a history of transient ischemic attack (TIA) pre-dementia. Cortical and subcortical infarcts were among the lesions observed on computer-assisted tomography and magnetic resonance imaging scans with significant white matter lesions also present in some patients. Placebo-treated patients demonstrated stable cognitive and global function over the 24 weeks of the study. These observations suggest that the patients enrolled in these trials have a broad range of CVD, and are different from those enrolled in AD trials.
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PMID:Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia. 1241 58

Many cases of age-related cognitive dementia are caused by cerebrovascular lesions, and various vascular syndromes can lead to cognitive impairment and dementia. Repeated cortical infarcts due to embolic disease of the heart or major cerebral vessels can cause progressive deterioration towards dementia and incapacitation. In classic multi-infarct dementia, cognitive deterioration is stepwise rather than smoothly progressive. While diagnostic technologies have vastly improved and added to general knowledge of the pathology of cerebrovascular disease, MRI, PET, and transcranial Doppler scans have demonstrated that significant white matter change is possible without clinically recognized TIA or completed stroke. In addition, patients may have initial complaints that are not serious enough to produce changes on mental status examination. Many patients have mixed dementia, exhibiting aspects of both degenerative brain disease and clinical evidence of strokes or significant changes on MRI scan. The overlap between vascular and degenerative disease is significant, yet the exact interaction of the pathophysiology of the vascular lesions and the degenerative changes is not known. The treatment of vascular or mixed dementia involves control of the risk factors for continued vascular events and treatment with the cholinesterase inhibitors.
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PMID:Vascular dementia. 2247 Feb 55

In this article, I discuss the adaptation of antidementia drugs for Behavioral and Psycho- logical Symptoms of Dementia (BPSD). During the last few years, a large body of evidence has been accumulated to support the use of antidementia medication for BPSD in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients. On the selection of antidemen- tia drugs for BPSD, the following 3 factors should be considered : 1) the type of dementia the patients have (AD or DLB), 2) the type of drugs to be selected (cholinesterase inhibitors or memantine), and 3) the type of BPSD to be treated (such as delusions, hallucinations, agitation, and apathy). Cholinesterase inhibitors should be used for the treatment of people with DLB, especially BPSD. On the other hand, in AD patients with severe BPSD such as agitation and hallucinations, memantine should be initially considered. Pharmacological treatment of wander- ing and disinhibition in patients with dementia remains a challenge. As BPSD can cause marked distress for both the patient and caregiver, clinicians are required to treat the symptoms effectively. The consensus statement focuses on the fact that pharmacotherapy and psychological interventions can be effective both for cognitive dysfunc- tion and BPSD. Total care for BPSD involves the combination of pharmacotherapy with a non- pharmacological approach.
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PMID:[The Adaptation of Anti-dementia Drugs for BPSD]. 3062 May 4