The effect of entacapone on homocysteine levels in Parkinson disease.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
J Hubble
Publications and source records attributed to J Hubble.
Characterisation of hydrogel gel swelling by molecular exclusion.
A facile method for the characterization of hydrogel swelling is described which is based on the determination of changes in the liquid phase concentration of an excluded tracer as gel swells in a constant volume system. The utility of this approach is demonstrated with two responsive hydrogel preparations, one where swelling is influenced by system pH, the other by changes in specific solute concentration.
Dextrans↗
An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease patients experiencing wearing-off.
OBJECTIVES: To evaluate the tolerability, safety and efficacy of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease (PD). BACKGROUND: Levodopa provides the most effective symptom control for the treatment of Parkinson's disease (PD). However, its long-term use is limited by the development of motor complications such as wearing-off. Catechol-O-methyltransferase (COMT) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce 'off' time. Stalevo is a new levodopa product that combines carbidopa, levodopa and entacapone in one tablet. Clinical studies have not been reported with this compound. DESIGN METHODS: An open-label, multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off, with (n = 39) and without (n = 130) mild dyskinesia. Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks. Assessments included tolerability measures, adverse events profile, the disease-specific quality of life instrument PDQ-39, UPDRS parts II, III, and question 39 and investigator and patient global clinical assessments. RESULTS: 14 subjects (8%) discontinued treatment with Stalevo, of which 12 (7%) were due to adverse events. 11/130 (8.5%) subjects developed new onset dyskinesia and 17/39 (43.6%) of patients with existing dyskinesia reported a worsening in their dyskinesia. However, this was managed by a change in dose in 21.4% of patients and in another 10.7% dyskinesias resolved without any need for dose adjustment. Other side effects were infrequent and mild, the most common being nausea (12.4%) dizziness (6.5%) and somnolence (6.5%). Stalevo treatment resulted in significant improvements in PDQ-39 and UPDRS (II + III) scores (p < 0.001). Assessment of 'off' time demonstrated a reduction in off time in 32% of patients, compared with an increase in 7% of patients. Improvements were noted by both investigator (68.1%) and patient (68.6%) assessments. CONCLUSIONS: Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe, well tolerated and resulted in clinical improvement.
Adult↗
NAD-sensitive hydrogel for the release of macromolecules.
A hydrogel membrane containing immobilized ligands and receptors was synthesized and investigated for the controlled diffusion of test proteins (cytochrome C and hemoglobin). Both Cibacron blue (ligand) and lysozyme (receptor) were covalently linked to dextran molecules that were subsequently crosslinked to form a gel. The resulting stable hydrogels contained both covalent and affinity crosslinks such that their intrinsic porosities were sensitive to competitive displacers of the affinity interaction between lysozyme and Cibacron blue. Transport experiments in a twin chamber diffusion cell showed that as NAD was added to the donor side, the dissociation of the binding sites between the Cibacron blue and the lysozyme led to an increase in protein diffusion through the hydrogel. The results showed that addition of NAD caused a saturable concentration-dependent increase in the transport of both cytochrome C and hemoglobin. This effect was shown to be both specific and reversible.
Coated Materials, Biocompatible↗
Double-blind, placebo-controlled study of entacapone in levodopa-treated patients with stable Parkinson disease.
BACKGROUND: The catechol O-methyltransferase inhibitor entacapone acts by extending the elimination half-life of levodopa and is currently approved as an adjunct to levodopa for the treatment of patients with Parkinson disease (PD) with motor fluctuations. OBJECTIVE: To determine if the addition of entacapone administration provides benefit to levodopa-treated PD patients who have a stable response to levodopa and do not experience motor complications. DESIGN: Prospective, double-blind, placebo-controlled trial. SETTING: Outpatient multicenter study. PATIENTS: Female and male patients 30 years or older with idiopathic PD receiving stable doses of levodopa or carbidopa with or without other dopaminergic therapies and who did not experience motor fluctuations were eligible for the study. MAIN OUTCOME MEASURES: Parkinsonian function and quality of life. RESULTS: The addition of entacapone did not improve motor scores on the Unified Parkinson's Disease Rating Scale in levodopa-treated PD patients who did not experience motor fluctuations. The mean +/- SE adjusted change between baseline and final treatment visit was -0.9 +/- 0.35 in the entacapone group and -0.8 +/- 0.35 in the placebo group (P = .83). Significant improvement with entacapone treatment was detected in several quality-of-life measures, including the Parkinson Disease Questionnaire 39, the 36-item Short-Form Health Survey, the Parkinson's Symptom Inventory, and investigator and subject Clinical Global Assessments. The drug was well tolerated by patients in this population. CONCLUSIONS: The catechol O-methyltransferase inhibitor entacapone, used as an adjunct to levodopa in PD patients who do not experience motor fluctuations, does not improve Unified Parkinson's Disease Rating Scale motor scores but does improve a variety of quality-of-life measures.
Aged↗
Scale and corrosion control with combined dolomite/calcite filter.
Water quality is a major operational issue for boiler operation and control. If the water is hard scale control is required and if it is soft then corrosion control is an issue. Here a two stream boiler test rig has been used to test the effect a fixed bed filter has on the scaling and corrosion properties of both hard and soft waters. The filter effectively controlled the pH, hardness and alkalinity of both waters leading to significant decreases in scale formation and effective control of corrosion.
Calcium Carbonate↗
Isocratic separation of monosaccharides using immobilized Concanavalin A.
The successful fractionation of a mixture of monosaccharides using an immobilized lectin column operating under isocratic conditions is described. The key factors for effective separation were found to be sample size, feed velocity and column length. Under optimal conditions it was possible to obtain complete resolution of a mixture of L-arabinose, D-fructose and D-mannose in less than 40 min.
Arabinose↗
A reversible hydrogel membrane for controlling the delivery of macromolecules.
Glucose-sensitive hydrogel membranes have been synthesized and characterized for their rate-of-delivery of macromolecules. The mechanism for changing this rate is based on variable displacement of the affinity interaction between dextran and concanavalin A (con A). Our main objective was to characterize the diffusion of model proteins (insulin, lysozyme, and BSA) through the membrane, in response to changes in environmental glucose concentrations. Membranes were constructed from crosslinked dextrans to which con A was coupled via a spacer arm. Changes in the porosity of the resulting hydrogel in the presence of glucose led to changes in the diffusion rate observed for a range of proteins. Gels of specified thickness were cast around to nylon gauze support (pore size, 0.1 mm) to improve mechanical strength. Diffusion of proteins through the gel membrane was determined using a twin-chamber diffusion cell with the concentrations being continuously monitored using a UV-spectrophotometer. Changes in the transport properties of the membranes in response to glucose were explored and it was found that, while 0.1M D-glucose caused a substantial, but saturateable, increase in the rates of diffusion of both insulin and lysozyme, controls using glycerol or L-glucose (0.1M) had no significant effect. Sequential addition and removal of external glucose in a stepwise manner showed that permeability changes were reversible. As expected, diffusion rates were inversely proportional to membrane thickness. A maximum increase in permeability was observed at pH 7.4 and at 37 degrees C. The results demonstrate that this hydrogel membrane functions as a smart material allowing control of solute delivery in response to specific changes in its external environment.
Anti-Bacterial Agents↗
Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.
OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.
Age of Onset↗
Effect of contact time and inhibitor concentration on the affinity mediated adsorption of cells to surfaces.
Cell detachment by shear stress under conditions of laminar flow was used to investigate the effect of incubation time and soluble binding competitors on affinity mediated cell/surface interactions. Fractional attachment between yeast and a Concanavalin A (Con A) coated surface was studied as a function of adhesion time prior to exposure to shear in a parallel plate flow chamber. Two, four and sixteen hours adhesion times gave rise to significantly different fractional attachment profiles, with four hours giving greater cell retention.The effect of dextran as a competitive displacer of pre-attached cells was also examined using a number of exposure regimes. While the presence of dextran in the displacement buffer led to higher fractional displacement of pre-attached cells, this effect was magnified if an equilibration period between dextran solution and pre-attached cells was allowed before detachment was attempted. The decline in fractional attachment increased with incubation time up to 30 min, with longer periods resulting in a smaller effect. Pre-incubation of the Con A surface with dextran prior to the introduction of cells led to a 60% reduction in attachment.Attempts to determine critical shear values were complicated by the presence of a tightly bound cell fraction of approximately 15% that was not removed at the highest shear values used.
Journal Article↗
The kinetics of affinity-mediated cell-surface attachment.
Data and a semi-empirical model are presented that describe the affinity interaction of yeast cells with a Concanavalin A derivatised surface. The model uses 3 parameters to describe the time course of cell attachment from a flowing suspension of yeast cells, over a range of flow rates, and gives an effective global fit to the data obtained. Further modifications allow the effects of a soluble competitor (glucose) on binding to be quantified in terms of a saturation effect, and an effective global fit is obtained. A comparison was made between the relationship between steady-state attached fraction and applied shear with similar data reported earlier (Ming, F. et al, 1998) for the detachment of pre-adsorbed cells. This shows that there is an order of magnitude difference between the forces required to effect complete detachment in the two systems, and that the nature of the relationship between shear and attached fraction is profoundly different. The magnitude of this time-dependent stabilization might be explained in terms of a progressive reorientation of cell relative to the surface such that the number of bonds is maximized.
Journal Article↗
Linear pharmacokinetic behavior of ropinirole during multiple dosing in patients with Parkinson's disease.
The objectives of this study were to measure the pharmacokinetics of ropinirole at steady state when the drug is used as an adjunct to L-dopa and evaluate the long-term tolerability of ropinirole in this indication. Twenty-four patients who were taking L-dopa for Parkinson's disease and experiencing a lack of symptomatic control were recruited. Patients received open-label adjunctive treatment with ropinirole for up to 2 years. The starting dose was 0.5 mg bid, which could be titrated to a maximum of 6.0 mg tid. Ropinirole demonstrated approximately dose-linear pharmacokinetics at steady state; corresponding values were higher during tid than bid dosing. A reduction in mean L-dopa dose was maintained throughout the trial. The combination of L-dopa and ropinirole was generally well tolerated, with only 1 patient withdrawing from treatment because of adverse events. Thus, ropinirole shows approximately linear steady-state pharmacokinetics and a good safety profile when administered with L-dopa.
Adult↗
Benefits of COMT inhibitors in levodopa-treated parkinsonian patients: results of clinical trials.
Recent prospective, double-blind, placebo-controlled trials have examined the long-term effects of the catechol-O-methyl transferase (COMT) inhibitors entacapone and tolcapone as adjuncts to levodopa in PD patients with wearing-off motor fluctuations. These studies demonstrate that both tolcapone and entacapone provide PD patients who suffer motor fluctuations with increased "on" time, decreased "off" time, and improved motor scores in comparison to placebo-treated patients. The improvement was observed rapidly, often being evident within days of initiating the intervention. Benefits persisted throughout the duration of the study. Increased dopaminergic side effects were observed with both drugs, but these were generally readily controlled by a concomitant reduction in levodopa dose. Tolcapone was associated with some instances of explosive diarrhea and liver enzyme elevation so that periodic monitoring of liver function was recommended. These did not occur with entacapone, and monitoring of liver function was not required. This report reviews the results of the multi-center trials of entacapone, and tolcapone.
Benzophenones↗
The alpha-synuclein gene is not a major risk factor in familial Parkinson disease.
Explore the source record for details and available documents.
Adult↗
A model of multivalent ligand-receptor equilibria which explains the effect of multivalent binding inhibitors.
Quantitative relationships based on multivalent ligand receptor binding equilibria are developed which can describe the enhanced binding observed when polyvalent ligands are used as inhibitors of cell/cell interactions. This theory is able to explain the many orders of magnitude difference reported between the apparent dissociation constants determined for the interaction of Entamoeba histolytica membrane receptors with mono and multivalent N-Acetylgalactosaminide inhibitors. Given two experimentally accessible constants the theory provides a framework for the quantitative evaluation of custom designed polyvalent inhibitors of lectin and antibody mediated interactions.
Animals↗
Autosomal recessive juvenile parkinsonism maps to 6q25.2-q27 in four ethnic groups: detailed genetic mapping of the linked region.
Parkinson disease (PD) is a common neurodegenerative condition associated with degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. There is increasing evidence that genetic factors play a role in the etiology of PD, although genetic heterogeneity is likely. An autosomal dominant syndrome with many similarities to sporadic PD has been mapped to 4q21-22 in a large Italian pedigree and has been found to be due to mutation of the alpha-synuclein gene. However, this gene appears to account for only a minority of PD, and a susceptibility locus for autosomal dominant parkinsonism has recently been mapped, on 2p13. Autosomal recessive juvenile parkinsonism (JP), which shows marked clinical similarity to PD, maps to 6q25.2-q27. We found linkage to this region in a group of 15 families from four distinct ethnic backgrounds. A full genomic screen excluded other candidate regions. We have constructed a detailed genetic map of the linked region and have mapped the position of the manganese superoxide dismutase gene (SOD2). Recombination events restricted the JP locus to a 6.9-cM region and excluded SOD2. The apparent homozygosity for null alleles at D6S955 in one family suggested a deletion and finer localization of the JP locus.
Age of Onset↗
High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.
Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.
Aged↗
Dissociation of multivalent antibody-antigen interactions.
Explore the source record for details and available documents.
Antigen-Antibody Reactions↗