Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00080 (Leaf)
 21,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days.
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PMID:Intracerebroventricular bethanechol chloride infusion in Alzheimer's disease. Results of a collaborative double-blind study. 257 89

In the central nervous system, the functions of microglia appear crucial after brain damage, when phagocytes eliminate cell debris, acting as the scavengers of the brain. Diseases where an active role for microglia has been proposed recently include Alzheimer's disease, the acquired immune deficiency syndrome (AIDS) and multiple sclerosis. Only recently has it been possible to obtain a microglial cell line retaining morphological and functional aspects of these cells and their secretory products. Sugar receptors are expressed by a variety of phagocytes in primary cultures, but in contrast, are absent on the majority of the described macrophage-like cell lines. We here establish, by 4 degrees C binding experiments, that this murine cell line, called BV-2, expresses a high level (9.86 +/- 0.91 x 10(5); n = 3) of beta-glucan receptors. At 37 degrees C, BV-2 cells show high phagocytic power that can only be inhibited by the free polysugar beta-laminarin (a poly-glucose) and not by mannan (a poly-mannose) as described for macrophages. The beta-glucan receptor expressed by the microglial cell line BV-2 is fully functional in phagocytosis of unopsonized heat-killed yeast particles.
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PMID:Functional beta-glucan receptor expression by a microglial cell line. 782 4

A decrease in the activity of choline acetyltransferase (ChAT) has been well documented in brains from individuals with Alzheimer's disease (AD) (Bird et al., 1983; McGeer, 1984). Decreased ChAT activity was also found in dialysis encephalopathy victims, but this reduction was less marked than that observed in AD (Yates et al., 1980). The involvement of aluminum in the etiology of AD has been proposed by some authors on the basis of abnormal concentration of aluminum in autopsied brain samples from AD patients (Krishnan et al., 1987), in the neurofibrillary tangles (Perl and Pendlebury, 1986) and the neuritic plaques (Candy et al., 1986). King (1984) hypothesized that elevated levels of aluminum contribute to the cholinergic deficits in AD. Aluminum is considered to be the causal factor in dialysis encephalopathy (Alfrey et al., 1976), particularly in young children with azotemia (Andreoli et al., 1984). Several animal studies demonstrate in vivo an aluminum effect on ChAT (Yates et al., 1980; Hofstetter et al., 1987). The distribution of the cholinergic perikarya in the rat CNS has been established immunohistochemically using antisera to ChAT (Sofroniev et al., 1982). From the basal forebrain, ChAT positive fiber bundles could be followed to the olfactory bulb, neocortex and hippocampus (Ichikawa and Hirata, 1986). This paper examines the influence of aluminum chloride at different concentrations on the activity of ChAT in homogenates from basal forebrain and neostriatum of rats during postnatal growth.
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PMID:In vitro effect of aluminum chloride on choline acetyltransferase activity of the rat brain during postnatal growth. 816 40

Inconsistencies within results of case-control studies on Alzheimer's disease risk factors led to a search of the literature for a potential cofactor. Reduced cerebral blood flow was selected and literature was surveyed for evidence of a cerebral blood flow linkage with the more than 40 putative risks. Alcohol abuse, depression, head trauma, underactivity, old age, sleep disturbance, glucose utilization, Down's syndrome, and Parkinson's disease are risk factors where an association with reduced cerebral blood flow is documented. Studies were cited showing that improved cerebral blood flow is associated with factors thought to be helpful in Alzheimer's disease, such as education or occupational attainment, exercise, headache, smoking, and arthritis/anti-inflammatory drugs to the extent that aspirin is used. Sugar consumption is identified as a potential risk factor with glucose management in Alzheimer's disease also shown to involve reduced cerebral blood flow. An hypothesis is developed showing how compromised regional cerebral blood flow could fit as a cofactor for genetic, autoimmune, and neurotoxic aspects of Alzheimer's disease.
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PMID:Alzheimer's disease risk factors as related to cerebral blood flow. 873 67

The magnitude and importance of changes in scores of neuropsychological tests on retest in the elderly, especially over long time periods, is not well established. Three neuropsychological tests and one mental status test were initially administered to screen for potential dementia and were readministered to 380 of the surviving individuals 2.4 years later who either failed the screening examination or were an age matched control. Of the 380 women and men aged 65 and older, 56 were diagnosed as having Alzheimer disease (AD), 82 as at risk for developing AD, and 242 as having normal cognition. The present report focuses on changes in test scores between the two visits. In the normal and at risk groups, significant improvements were seen on retest of the Visual Reproduction Test (VRT), the Trails B test, and the Mini-Mental Status examination; verbal fluency decreased, and savings score of the VRT showed small variations. On most tests, scores of the AD group decreased. Practice effects, biases, and other variables may have played a role in the improvements seen in those labeled normal and at risk. If these results are confirmed, savings score of the VRT (which remained stable over time in normals and individuals at risk and decreased in patients with dementia) and verbal fluency (which decreased in all groups) may be better measures of true cognitive performance than the other tests that we evaluated.
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PMID:Effects of sequential neuropsychological testing of an elderly community-based sample. 887 78

On Wednesday, March 23, 51 older Americans came to Washington, DC, to deliver their unique messages concerning the need for long-term care and a health care system responsive to the needs of older Americans. HealthRIGHT, a coalition created to capture Americans' views on the health care system and what needs to be done to improve it, orchestrated the event. In an extraordinary briefing session in the Rayburn House Office Building, First Lady Hillary Rodham Clinton was present with congressional leaders to hear these stories. Several of the witnesses focused on Alzheimer's patients or their caregivers. CARING is pleased to include their stories here, as testimony to the major effect this terrible disease can have on a family.
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PMID:Heroes of health care: a window on caregiver burden. 1017 29

This study was undertaken to examine the relationship between two different competencies, financial and medical decision making, and explore whether neuropsychological testing can identify a common underlying cognitive operation impaired in patients with AD. The objective was to examine the neuropsychological predictors of financial and medical decision-making competencies in patients with Alzheimer's disease (AD). Twenty individuals with mild to moderate AD and 20 control subjects matched for age and education were evaluated at a university medical center. All participants were administered a financial competency questionnaire, a competency test for medical decision making, and a set of standardized neuropsychological tests selected to reflect cognitive processes theoretically related to competency. In addition, an informant provided information regarding banking history for each participant. AD patients performed more poorly on all measures, including both measures of competency, which were highly related (R = .718, P < .001). Two tests, Trails A and Word List Recall, were significantly correlated with both competency measures, with Trails A predicting over 85% of the variance in competency scores. Trails A discriminated competent from not competent participants with an accuracy ranging from 77% to 82%. Measures of financial and medical decision-making competency were significantly correlated among patients with AD. One brief neuropsychological test of attention, Trails A, proved to be highly predictive of performance on both competency measures and useful in the discrimination of competent performance on these measures and by informant report.
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PMID:Attention: neuropsychological predictor of competency in Alzheimer's disease. 1061 68

Allergic reactions due to contact with different parts of the ancient tree Ginkgo biloba L. have repeatedly been reported. Provocation tests in patients and animal experiments have identified alkylphenols such as ginkgolic acids as causative constituents. Leaf extracts from Ginkgo are widely used to treat peripheral or cerebral circulatory disorders and Alzheimer's disease. Since alkylphenols are also present in leaves, potential allergic and other immunological hazards of such preparations have to be carefully controlled. Thus, we have evaluated if the popliteal lymph node assay (PLNA) in the mouse may represent a suitable model for the detection of constituents with immunotoxic properties in a complex mixture of biologically active agents such as plant extracts. Subplantar injection (2 mg) of a crude aqueous-ethanolic extract from Ginkgo leaves caused a significant lymphoproliferative reaction (LPR) in the ipsilateral popliteal lymph node. PLNA-active compounds in this extract could be enriched in the lipophilic phase by liquid-liquid partition between heptane and water. Chemical analysis of the heptane extract revealed the presence of a high concentration of alkylphenols (approx. 30%) and further subfractionation indicated that the enlargement of the popliteal lymph node was mainly due to the content of ginkgolic acids. This presumption was corroborated by observing a similar LPR following injection of a purified mixture of ginkgolic or hydroginkgolic acids. Thus, our experiments confirm that Ginkgo leaf extracts may contain constituents with immunotoxic properties, underlining the need to apply adequate production procedures to guarantee the completest possible removal of these compounds. The PLNA appears to represent a simple test model for the detection, characterisation and control of ingredients with potential immunotoxic side effects in complex herbal drugs.
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PMID:Evidence for immunotoxic effects of crude Ginkgo biloba L. leaf extracts using the popliteal lymph node assay in the mouse. 1068 5

A Phase I, double-blind, placebo-controlled, single-dose, escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics, Inc.) was conducted in healthy elderly volunteers. This trial was designed to evaluate single-dose safety, tolerability, and pharmacokinetics. Potential cognitive domains that might benefit from AIT-082 were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease (AD). Preclinical studies indicate that AIT-082 has memory-enhancing properties, stimulates neuritogenesis, and upregulates neurotrophic factors. Subjects received a single oral dose of AIT-082 or placebo on a weekly basis for 5 wk. All patients received a placebo dose at baseline. Six subjects received increasing doses of AIT-082 over the next 4 wk at doses of 0.6, 2.0, 6.0, and 20.0 mg of AIT-082 per kilogram of body weight. Two subjects received placebo throughout the trial. Nine subjects were recruited. One subject was withdrawn after the third treatment visit owing to poor venous access. There were no serious adverse events. The drug was well-tolerated. The time to peak drug concentration was approx 85 min with an elimination half-life of approx 17.6 h. Performance on the Number Comparison, Symbol Digit, and Trails A tests improved with AIT-082 dosing compared to baseline (placebo). In conclusion, AIT-082 was rapidly absorbed by the oral route with a half-life suitable for once daily dosing. No problems with tolerability or safety were demonstrated.
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PMID:A phase I study of AIT-082 in healthy elderly volunteers. 1205 47

Recent studies using Wide Range Achievement Test-Revised (WRAT-R) Reading scores as estimates of premorbid abilities have demonstrated that distinct neuropsychological deficit profiles may be associated with specific cognitive disorders such as traumatic brain injury [Brain Inj. 9 (1995) 377] and lupus [Appl. Neuropsychol. 7 (2000) 96], and that these deficit scores predict both functional and financial outcomes [J. Head Trauma Rehab. 14 (1999) 220]. Although the main cognitive deficits associated with senile dementia of the Alzheimer's type (SDAT) are well known, the relative degree of impairment in each has yet to be adequately determined. The present study calculated indices of relative decline (zDiff) for 32 patients with probable SDAT by comparing estimates of premorbid functioning to concurrent neuropsychological test scores. The results suggest that intelligence is least declined in SDAT [Wechsler Adult Intelligence Scale-Revised (WAIS-R) FIQ, zDiff=-0.72], followed by attention [Wechsler Memory Scale-Revised (WMS-R) Attention Index, zDiff=-1.14], memory (WMS-R General Memory, zDiff=-2.12; WMS-R Delay Memory, zDiff=-2.33), speed of processing (Trails A, zDiff=-2.85), and cognitive flexibility (Trails B, zDiff=-5.33). Clinical and research implications are discussed.
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PMID:Neuropsychological deficit profiles in senile dementia of the Alzheimer's type. 1458 27


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