Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002395 (Alzheimer's disease)
 110,584 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid and reliable measurement of acetylcholinesterase (AChE) activity is of crucial importance to the pharmacodynamic monitoring of anticholinesterase drugs. A new assay has been developed to measure AChE from 10 microliter samples of capillary blood. AChE activity was calculated from the change in pH of the reaction medium caused by the hydrolysis of acetylcholine and measured with a highly sensitive differential pH apparatus (CL-10, Eurochem, Rome, Italy). Interference by butyrylcholinesterase was eliminated by a specific inhibitor, quinidine sulfate. The assay lasts 1 min. The coefficient of variation (CV) for replicated measurements was 2.8% (3267 U/L, n = 33). Linearity ranged from 0 to 10,000 U/L. The correlation coefficient between the new technique and Ellman's colorimetric method on washed erythrocytes was r = 0.987 (y = 1.299x - 63, n = 29). The correlation coefficient between assays on capillary and venous samples was r = 0.979 (y = 0.974x + 174, n = 47). A cross-laboratory validation study was performed in 10 centers using glycerol-stabilized hemolysates with normal and reduced AChE activity. Samples were assayed in triplicate. The within- and between-laboratory CVs for samples with normal AChE activity (6,018 U/L) were 2.2 and 8.1%, respectively. The new method was applied to a double-blind, placebo-controlled multicenter study of eptastigmine in Alzheimer patients and proved to be a simple, noninvasive, rapid, and reliable method for pharmacodynamic monitoring of this drug.
Ther Drug Monit 1995 Jun
PMID:A patient-side technique for real-time measurement of acetylcholinesterase activity during monitoring of eptastigmine treatment. 762 18

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

Drug trials designed to modify the progression of Alzheimer's disease (AD) have required the development of mental state and behavior evaluation instruments that are sensitive to cognitive decline and measure skills useful in everyday living. We describe a videotaped home behavior (VHB) assessment instrument with high construct validity and reliability and a strong relationship to criterion references. The VHB was employed to test the hypothesis that aluminum is an important pathogenic factor in AD. The trivalent chelating agent desferrioxamine (DFO), 125 mg i.m. twice daily five days per week, was used in a randomized single-blind, oral lecithin, placebo-controlled clinical trial in 48 patients with AD. Analysis showed that the treatment and no-treatment groups were closely matched at entry into the trial but that the rate of decline, as measured by the VHB over 2 years of observation, was twice as rapid in the no-treatment group compared with the DFO-treated group. Furthermore, trace-metal analysis of autopsied brain confirmed that extended treatment with DFO lowered neocortical brain aluminum concentrations to near control concentrations. Aluminum ion-specific chelation may be a useful palliative treatment for AD, and further clinical trials are indicated.
Ther Drug Monit 1993 Dec
PMID:Desferrioxamine and Alzheimer's disease: video home behavior assessment of clinical course and measures of brain aluminum. 812 2

A new high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of tacrine (THA), nimodipine, and their three metabolites (MI, MII, and MIII) using a 1-ml plasma sample volume. A liquid-liquid extraction procedure was coupled with a reverse-phase HPLC separation. Quantification was performed by fluorometric detection for THA and metabolites and by ultraviolet detection for nimodipine and metabolites. Peak-height ratios were linear across the ranges 0.5 to 100 micro/l for THA and its three metabolites; 2 to 500 microg/l for nimodipine, MII, and MIII; and 4 to 500 microg/l for MI. Correlation coefficients were better than 0.998 for all compounds. Accuracy and precision were less than 12% for the entire concentration range for each substance. This method is sensitive and selective. Analysis of plasma samples collected from patients with Alzheimer disease demonstrated that the assay is suitable for clinical and pharmacokinetic trials including drug-drug interactions studies.
Ther Drug Monit 1998 Aug
PMID:High-performance liquid chromatography with ultraviolet and fluorimetric detection for the simultaneous determination of tacrine, nimodipine, and their respective metabolites in the plasma of patients with Alzheimer disease. 971 68

A symposium on 'Neurodegenerative disorders: from management to disease modification', organized by Athena Neurosciences (a division of Elan Pharma Ltd) was held at the Royal College of Physicians in London. Speakers outlined recent clinical advances in understanding of the underlying mechanisms of conditions such as multiple sclerosis, Alzheimer's disease and Parkinson's disease.
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PMID:Management of neurodegenerative disorders. 1060 44

A new high-performance liquid chromatography (HPLC) assay method was developed for the therapeutic monitoring of tacrine. The method involved a simple protein precipitation by means of either acetonitrile or cold methanol followed by a fast isocratic separation on a CN column eluted in reversed-phase mode. The entire sample preparation took place in an HPLC vial and no further liquid transfer was required. The validation data showed that the assay method was precise, accurate, and robust. Analysis of more than 1,000 plasma samples collected from patients with Alzheimer disease demonstrates the suitability of the assay.
Ther Drug Monit 2000 Apr
PMID:Therapeutic drug monitoring of tacrine: simple and fast high-performance liquid chromatography assay method for its determination in human plasma. 1077 38

The binding of cocaine and cocaethylene to homogenates of both normal whole brain and whole brain with Alzheimer disease patients (Alzheimer brain) was investigated in vitro using equilibrium dialysis of the unlabelled drugs at 4 degrees C. Two binders of cocaine were characterized in normal brain (binder 1: Ka, 5.73 x 10(3) L/mol; Bo, 7.44 x 10(-5) mol/L) (binder 2: Ka, 1.54 x 10(3) L/mol; Bo, 2.50 x 10(-4) mol/L) and in Alzheimer brain (binder 1: Ka, 3.08 x 10(2) L/mol; Bo, 6.66 x 10(-4) mol/L) (binder 2: Ka, 8.74 x 10(1) L/mol; Bo, 4.30 x 10(-3) mol/L). For cocaethylene three binders were noted in normal brain (binder 1: Ka, 3.23 x 10(3) L/mol; Bo, 1.22 x 10(-4) mol/L) (binder 2: Ka, 3.10 x 10(3) L/mol; Bo, 2.01 x 10(-4) mol/L) (binder 3: Ka, 1.63 x 10(3) L/mol; Bo, 3.59 x 10(-4) mol/L) and two binders in Alzheimer brain (binder 1: Ka, 5.18 x 10(3) L/mol; Bo, 3.06 x 10(-5) mol/L) (binder 2: Ka, 3.36 x 10(3) L/mol; Bo, 7.75 x 10(-5) mol/L). The binding of cocaine to normal brain was much stronger than to Alzheimer brain (ten- to 100-fold), whereas the binding of cocaethylene was similar in normal and Alzheimer brain. Cocaine and cocaethylene binding to human brain was compared with cocaine and cocaethylene binding to other human tissues previously studied by this laboratory.
Ther Drug Monit 2000 Oct
PMID:Cocaine and cocaethylene binding to normal human brain and Alzheimer disease brain. 1103 72

Melatonin is a hormone synthesized in the pineal gland from tryptophan. It participates in several biological processes in the human being, such as circadian sleep rhythm, mood, reproductive processes and aging. Melatonin serum levels are increased in childhood and diminish importantly in older people. Serum levels are diminished in patients with insomnia and depressive mood. Experimentally, the melatonin inhibits the growth of mammary tumors in animals. With respect to endometrial cancer and Alzheimer's disease, the information is not conclusive. No changes have been found in melatonin levels in climacterical women. So its use has not fundament in postmenopausal women, however it can only be administered for short periods of time for the treatment of some sleep disturbances.
Med Sci Monit
PMID:Melatonin and climactery. 1120 81

Elan is developing AN-1792 as a potential immunotherapy for Alzheimer's disease (AD). It is currently in phase I trials [350904]. Phase II/III trials, running in parallel in the US and UK, are expected to start by the end of 2001 [375061], [383226], [401966]. American Home Products (AHP) are collaborating with Elan on research and development of an immunotherapy directed towards the beta-amyloid peptide, including AN-1792 and other potential products [361702]. In September 2000, an agreement was established between Elan, AHP and Cambridge Antibody Technology (CAT), whereby CAT are investigating anti-beta-amyloid human antibodies [394844]. In July 2000, Merrill Lynch predicted a possible late-2001 entry into pivotal trials with a potential NDA filing in 2004 [375966]. The clinical program is expected to take approximately four years [339630]. In April 2001, ABN Amro Hoare Govett stated that, if data from the large phase II trial expected to start late in 2001 satisfied FDA requirements, then Elan might be able to file an NDA in 2003, with a potential launch in 2005 [407412].
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PMID:AN-1792 (Elan). 1156 44

Reactive oxygen species, such as superoxide radicals, are thought to underlie the pathogenesis of various diseases. Almost 3 to 10% of the oxygen utilized by tissues is converted to its reactive intermediates, which impair the functioning of cells and tissues. Superoxide dismutase (SOD) catalyzes the conversion of single electron reduced species of molecular oxygen to hydrogen peroxide and oxygen. There are several classes of SOD that differ in their metal binding ability, distribution in different cell compartments, and sensitivity to various reagents. Among these, Cu, Zn superoxide dismutase (SOD1) is widely distributed and comprises 90% of the total SOD. This ubiquitous enzyme, which requires Cu and Zn for its activity, has great physiological significance and therapeutic potential. The present review describes the role of SODs, especially Cu, Zn SOD, in several diseases, such as familial amyotrophic lateral sclerosis (FALS), Parkinson's disease, Alzheimer's disease, dengue fever, cancer, Down's syndrome, cataract, and several neurological disorders. Mutations in the SOD1 gene cause a familial form of amyotrophic lateral sclerosis. The mechanism by which mutant SOD1 causes the degeneration of motor neurons is not well understood. Transgenic mice expressing multiple copies of FALS-mutant SOD1s develop an ALS-like motor neuron disease. Vacuolar degeneration of mitochondria has been identified as the main pathological feature associated with motor neuron death and paralysis in several lines of FALS-SOD1 mice. Various observations and conclusions linking mutant SOD1 and FALS are discussed in this review in detail.
Med Sci Monit 2002 Sep
PMID:Superoxide dismutase--applications and relevance to human diseases. 1221 58


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