- Email: [email protected]
P2-427: Combined nutrient incubation improves receptor function stimulation over single nutrient incubation in pheochromocytoma cells
Poster Presentations P2: P2-427
COMBINED NUTRIENT INCUBATION IMPROVES RECEPTOR FUNCTION STIMULATION OVER SINGLE NUTRIENT INCUBATION IN PHEOCHROMOCYTOMA CELLS
Martijn C. de Wilde, Inge Leenders, Almar A. M. Kuipers, Nick van Wijk, Patrick J. Kamphuis, Laus M. Broersen, Numico Research, Wageningen, Netherlands. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is characterized by memory loss as a consequence of reduced neurotransmission. Functional deterioration of neuronal components, especially membrane linked components like receptors, is thought to play a significant role. Indeed, deterioration of the cholinergic system is found already early in AD pathogenesis and involves reduction of acetylcholine levels but also reductions in acetylcholine receptors, in particular muscarinic M1 receptors. Former study has shown that membrane-targeted multi-nutrient intervention could increase agonist binding to muscarinic M1 receptors in rats, indicative for enhanced cholinergic neurotransmission. Methods: The current study set out to detect effects of single nutrient and nutrient combinations on receptor agonist binding in neuronal cells. To this end pheochromocytoma cells were incubated with individual nutrients from specific nutrient classes (PUFA’s, nucleotides, phospholipids, B-vitamins and antioxidants) or combinations of nutrients from different classes for 24 hours. Thereafter, a flex-station was used to measure agonist induced changes in membrane potential. In untreated cells it was shown that agonists induced dose-dependent changes in membrane potential. Sub-optimal doses of agonists were then applied to the supplemented cells. Results: The results show that cells incubated with single nutrients or combinations of 2 showed a minor change in membrane potential (approx. 2% increase compared to control). Cells incubated with combinations of nutrients from 3 classes showed an increase of approximately 20% while combining 4 classes resulted in a roughly 40% increase in membrane potential change. The combination of nutrients from all classes into one supplementation resulted in a 60% increase compared to untreated cells. Conclusions: Together, these results show that incubation with nutrients resulted in greater agonist-induced changes in membrane potential, suggesting stronger receptor stimulation. Moreover, agonistinduced changes in membrane potential were especially enhanced in cells incubated with specific combinations of nutrient classes. These results demonstrate that specific combinations of nutrients can effectively enhance receptor functioning and might offer an effective means to improve neurotransmission. P2-428
METHYLTHIONINIUM CHLORIDE VERSUS RIVASTIGMINE AND THEIR COADMINISTRATION EFFICACY IN REVERSING SCOPOLAMINE-INDUCED COGNITIVE DEFICITS IN A PHARMACOLOGICAL MOUSE MODEL OF ALZHEIMER’S DISEASE
Serena Deiana1, Charles Harrington1, Gernot Riedel1, Kwang Meng Seng2, Claude M. Wischik1, 1University of Aberdeen, Aberdeen, United Kingdom; 2TauRx Therapeutics Ltd., Singapore, Singapore. Contact e-mail: [email protected] Background: The involvement of the cholinergic system in cognition as well as its role in age-related cognitive decline and Alzheimer disease (AD) has been extensively studied. Cholinergic enhancers, such as acetyl cholinesterase inhibitors (AChEIs), are used for temporary symptomatic treatment of AD. AChEIs, however, improve only certain symptoms and do so for a limited period, without affecting underlying disease progression. Methylthioninium chloride (MTC) is an inhibitor of tau aggregation and, in addition, has a broad range of potential biological actions, including antioxidant and metabolic-enhancing activities. We have examined its activity in relation to the AChEI, rivastigmine (Exelon®) Methods: MTC was tested for its anti-amnesic abilities in a pharmacological model of AD in which amnesia was induced by acute administration of scopolamine in
T499
wild-type mice. Their spatial learning and memory were tested in the water maze, a task that assesses hippocampal-dependent cognition, which is impaired in AD. MTC was administered after scopolamine either at a fully effective dose or at a sub-effective dose co-administered with rivastigmine. Results: MTC, on a weight basis, was less toxic and more effective than rivastigmine when the drugs were administered singly after scopolamine. Although rivastigmine only reversed the scopolamine-induced deficits in learning, MTC reversed both short- and long-term memory in addition to the learning deficits. Co-administration of sub-effective doses of rivastigmine and MTC elicited a temporal synergy in reversing learning deficits and a full reversal of scopolamine-induced memory impairments at subefficacy doses for each drug individually. There were no non-specific side effects of MTC in this paradigm. Conclusions: The study indicates that MTC, in addition to its activity as a Tau Aggregation Inhibitor, also has symptomatic activity. It is able to reverse a pharmacological cholinergic deficit and is more affective in this respect than an established AChEI. When combined with the AChEI, the symptomatic efficacy of MTC was enhanced. P2-429
NURSING PROTOCOL IN DEMENTIA: A BRAZILIAN EXPERIENCE
Ceres Eloah Lucena Ferretti, Paulo Henrique Ferreira Bertolucci, Federal University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: Nonpharmacological approach can be very useful on dementia management. The Nursing protocol is an assessment instrument that was created with geriatric and neurological focus. Methods: The protocol can be used to all of disease stages. It’s applied on outpatients belonged to the Behavioral Neurology Unit, of Federal University of Sa˜o Paulo or, if necessary, at home dwelling patients by an expertise nurse. The instrument was designed to attend to assistance and research purposes. Generally, the protocol is applied in two moments and after the first interview with the patient and their caregiver, whether there are identified biopsychosocial problems, either with patients or with caregivers, nursing diagnosis and interventions are implemented. These interventions are based on NANDA taxonomy with respect to OREM theoretical model of nursing. The results of the first interview are compared to the final assessment. Results: Previous longitudinal and quasi-experimental studies showed that this model can be functional. We founded that some results showed a statistically significant improvement. ADLs dependencies (Z ⫽ 2.4; p ⫽ 0.014); behavioral disorders: total score on the NPI (Z⫽-3.1; p⫽0.002); aggressiveness (Z⫽ -2.3; p ⬍ 0.001); anxiety: (Z⫽ -2.2; p⫽0.026) and distress to the caregivers (Z⫽-2.2; p⫽0.030). Conclusions: Controlled studies should be accomplished to verify the efficacy of this intervention model, as the results may not be conclusive. P2-430
THE ASSOCIATION BETWEEN USE OF INTRAVENOUS IMMUNOGLOBULIN AND RISK OF ALZHEIMER’S DISEASE AND RELATED DISORDERS
Howard Fillit1, Gregory Hess2,3, Jerrold Hill2, 1Mount Sinai School of Medicine, New York, NY, USA; 2Surveillance Data Inc., Plymouth Meeting, PA, USA; 3Leonard Davis Institute, University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: Immunotherapy for Alzheimer⬘s disease (AD) has gained considerable interest. Recent studies indicate that immunotherapy with intravenous immunoglobulin (IVIg) for AD has clinical efficacy. Since IVIg is currently in use in clinical practice for other indications, we determined whether use of IVIg in usual care is associated with a lower risk of AD and related disorders (ADRD). Methods: A retrospective casecontrol study of patients age ⱖ65 was conducted using data available on 22 million age-qualified patients from the Surveillance Data Inc. database of medical claims. Study cases initiated IVIg treatment between 4/2001 and 9/2004, had claims data 1 year prior to index date of IVIg treatment to
COMBINED NUTRIENT INCUBATION IMPROVES RECEPTOR FUNCTION STIMULATION OVER SINGLE NUTRIENT INCUBATION IN PHEOCHROMOCYTOMA CELLS
Martijn C. de Wilde, Inge Leenders, Almar A. M. Kuipers, Nick van Wijk, Patrick J. Kamphuis, Laus M. Broersen, Numico Research, Wageningen, Netherlands. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is characterized by memory loss as a consequence of reduced neurotransmission. Functional deterioration of neuronal components, especially membrane linked components like receptors, is thought to play a significant role. Indeed, deterioration of the cholinergic system is found already early in AD pathogenesis and involves reduction of acetylcholine levels but also reductions in acetylcholine receptors, in particular muscarinic M1 receptors. Former study has shown that membrane-targeted multi-nutrient intervention could increase agonist binding to muscarinic M1 receptors in rats, indicative for enhanced cholinergic neurotransmission. Methods: The current study set out to detect effects of single nutrient and nutrient combinations on receptor agonist binding in neuronal cells. To this end pheochromocytoma cells were incubated with individual nutrients from specific nutrient classes (PUFA’s, nucleotides, phospholipids, B-vitamins and antioxidants) or combinations of nutrients from different classes for 24 hours. Thereafter, a flex-station was used to measure agonist induced changes in membrane potential. In untreated cells it was shown that agonists induced dose-dependent changes in membrane potential. Sub-optimal doses of agonists were then applied to the supplemented cells. Results: The results show that cells incubated with single nutrients or combinations of 2 showed a minor change in membrane potential (approx. 2% increase compared to control). Cells incubated with combinations of nutrients from 3 classes showed an increase of approximately 20% while combining 4 classes resulted in a roughly 40% increase in membrane potential change. The combination of nutrients from all classes into one supplementation resulted in a 60% increase compared to untreated cells. Conclusions: Together, these results show that incubation with nutrients resulted in greater agonist-induced changes in membrane potential, suggesting stronger receptor stimulation. Moreover, agonistinduced changes in membrane potential were especially enhanced in cells incubated with specific combinations of nutrient classes. These results demonstrate that specific combinations of nutrients can effectively enhance receptor functioning and might offer an effective means to improve neurotransmission. P2-428
METHYLTHIONINIUM CHLORIDE VERSUS RIVASTIGMINE AND THEIR COADMINISTRATION EFFICACY IN REVERSING SCOPOLAMINE-INDUCED COGNITIVE DEFICITS IN A PHARMACOLOGICAL MOUSE MODEL OF ALZHEIMER’S DISEASE
Serena Deiana1, Charles Harrington1, Gernot Riedel1, Kwang Meng Seng2, Claude M. Wischik1, 1University of Aberdeen, Aberdeen, United Kingdom; 2TauRx Therapeutics Ltd., Singapore, Singapore. Contact e-mail: [email protected] Background: The involvement of the cholinergic system in cognition as well as its role in age-related cognitive decline and Alzheimer disease (AD) has been extensively studied. Cholinergic enhancers, such as acetyl cholinesterase inhibitors (AChEIs), are used for temporary symptomatic treatment of AD. AChEIs, however, improve only certain symptoms and do so for a limited period, without affecting underlying disease progression. Methylthioninium chloride (MTC) is an inhibitor of tau aggregation and, in addition, has a broad range of potential biological actions, including antioxidant and metabolic-enhancing activities. We have examined its activity in relation to the AChEI, rivastigmine (Exelon®) Methods: MTC was tested for its anti-amnesic abilities in a pharmacological model of AD in which amnesia was induced by acute administration of scopolamine in
T499
wild-type mice. Their spatial learning and memory were tested in the water maze, a task that assesses hippocampal-dependent cognition, which is impaired in AD. MTC was administered after scopolamine either at a fully effective dose or at a sub-effective dose co-administered with rivastigmine. Results: MTC, on a weight basis, was less toxic and more effective than rivastigmine when the drugs were administered singly after scopolamine. Although rivastigmine only reversed the scopolamine-induced deficits in learning, MTC reversed both short- and long-term memory in addition to the learning deficits. Co-administration of sub-effective doses of rivastigmine and MTC elicited a temporal synergy in reversing learning deficits and a full reversal of scopolamine-induced memory impairments at subefficacy doses for each drug individually. There were no non-specific side effects of MTC in this paradigm. Conclusions: The study indicates that MTC, in addition to its activity as a Tau Aggregation Inhibitor, also has symptomatic activity. It is able to reverse a pharmacological cholinergic deficit and is more affective in this respect than an established AChEI. When combined with the AChEI, the symptomatic efficacy of MTC was enhanced. P2-429
NURSING PROTOCOL IN DEMENTIA: A BRAZILIAN EXPERIENCE
Ceres Eloah Lucena Ferretti, Paulo Henrique Ferreira Bertolucci, Federal University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: Nonpharmacological approach can be very useful on dementia management. The Nursing protocol is an assessment instrument that was created with geriatric and neurological focus. Methods: The protocol can be used to all of disease stages. It’s applied on outpatients belonged to the Behavioral Neurology Unit, of Federal University of Sa˜o Paulo or, if necessary, at home dwelling patients by an expertise nurse. The instrument was designed to attend to assistance and research purposes. Generally, the protocol is applied in two moments and after the first interview with the patient and their caregiver, whether there are identified biopsychosocial problems, either with patients or with caregivers, nursing diagnosis and interventions are implemented. These interventions are based on NANDA taxonomy with respect to OREM theoretical model of nursing. The results of the first interview are compared to the final assessment. Results: Previous longitudinal and quasi-experimental studies showed that this model can be functional. We founded that some results showed a statistically significant improvement. ADLs dependencies (Z ⫽ 2.4; p ⫽ 0.014); behavioral disorders: total score on the NPI (Z⫽-3.1; p⫽0.002); aggressiveness (Z⫽ -2.3; p ⬍ 0.001); anxiety: (Z⫽ -2.2; p⫽0.026) and distress to the caregivers (Z⫽-2.2; p⫽0.030). Conclusions: Controlled studies should be accomplished to verify the efficacy of this intervention model, as the results may not be conclusive. P2-430
THE ASSOCIATION BETWEEN USE OF INTRAVENOUS IMMUNOGLOBULIN AND RISK OF ALZHEIMER’S DISEASE AND RELATED DISORDERS
Howard Fillit1, Gregory Hess2,3, Jerrold Hill2, 1Mount Sinai School of Medicine, New York, NY, USA; 2Surveillance Data Inc., Plymouth Meeting, PA, USA; 3Leonard Davis Institute, University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: Immunotherapy for Alzheimer⬘s disease (AD) has gained considerable interest. Recent studies indicate that immunotherapy with intravenous immunoglobulin (IVIg) for AD has clinical efficacy. Since IVIg is currently in use in clinical practice for other indications, we determined whether use of IVIg in usual care is associated with a lower risk of AD and related disorders (ADRD). Methods: A retrospective casecontrol study of patients age ⱖ65 was conducted using data available on 22 million age-qualified patients from the Surveillance Data Inc. database of medical claims. Study cases initiated IVIg treatment between 4/2001 and 9/2004, had claims data 1 year prior to index date of IVIg treatment to