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No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50346/1/410300420_ftp.pd

Antiepileptic Drug Actions

Antiepileptic drugs (AEDs) vary in their efficacy against generalized tonic-clonic, myoclonic, and absence seizures, suggesting different mechanisms of action. Phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) reduced the ability of mouse central neurons to sustain high-frequency repetitive firing of action potentials (SRF) at therapeutic free serum concentrations. Phenobar-bital (PB) and the benzodiazepines (BZDs), diazepam (DZP), clonazepam (CZP), and lorazepam (LZP), also reduced SRF, but only at supratherapeutic free serum concentrations achieved in treatment of generalized tonic-clonic status epilepticus. These AEDs interact with sodium channels to slow the rate of recovery of the channels from inactivation. The BZDs and PB enhanced Γ-aminobutyric acid (GABA) responses evoked on mouse central neurons by binding to two different sites on the GABA A receptor channel. BZDs increased the frequency of GABA receptor channel openings. In contrast, barbiturates increased the open duration of these channels. VPA enhanced brain GABA concentration and may enhance release of GABA from nerve terminals. Ethosuximide (ESM) reduced a small transient calcium current which has been shown to be involved in slow rhythmic firing of certain neurons. Reduction of SRF, enhancement of GABA-ergic inhibition, and reduction of calcium current may be, in part, the bases for A ED action against generalized tonic-clonic, myoclonic, and absence seizures, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65920/1/j.1528-1157.1989.tb05810.x.pd

Introduction and Symposium Overview

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65408/1/j.1528-1157.1999.tb00871.x.pd

Basic Living Expenses for the Canadian Elderly

Our research undertakes to determine the basic living expenses required by Canadian seniors living in different circumstances in terms of age, gender, city of residence, household size, homeowner or renter, means of transportation and health status. The paper develops required expenses for food, shelter, health care, transportation and miscellaneous. The research identifies the typical expenses of seniors in each of these categories. Using 2001 as our base year, we follow the US Elder Standard to build an elderly threshold for Halifax, Montreal, Toronto, Calgary and Vancouver. The research is unique because it is the first Canadian study of absolute basic living expenses tailored to seniors, rather than simply to adults in general. This information is important to seniors, prospective retirees, financial planners, policy makers and actuaries in assessing the minimum level of income required in retirement and the adequacy of savings and income security programs. Our conclusions suggest that individual circumstances, rather than age, are the primary drivers in determining the cost of these basic expenses. Seniors are a diverse group, particularly with respect to health, so it is important that seniors and financial planners do not blindly rely on a fixed replacement ratio or universal level of income when projecting the level of finances needed to retire. This research enables the reader to determine the threshold that is suited to a senior’s general circumstances.Retirement Income Adequacy; Absolute Measure; Elder Standard; Canadian Data

The Canadian Elder Standard - Pricing the Cost of Basic Needs for the Canadian Elderly

We determined the after-tax income required to fi nance basic needs for Canadian elders living with different circumstances in terms of age, gender, city of residence, household size, homeowner or renter status, means of transportation, and health status. Using 2001 as our base year, we priced the typical expenses for food, shelter, medical, transportation, miscellaneous basic living items and home-based long-term care for elders living in fi ve Canadian cities. This is the fi rst Canadian study of basic living expenses tailored to elders instead of adults in general, prepared on an absolute rather than a relative basis. We also accounted for an individual’s unique life circumstances and established the varying effect that they have on the cost of basic expenses, particularly for home care. We found that the maximum Guaranteed Income Supple ment and Old Age Security benefi t did not meet the cost of basic needs for an elder living in poor circumstances.Canadian seniors, poverty measure, economic security, aging-in-place, cost-of-living, absolute measure, home care

Antiepileptic Drug Mechanisms of Action

Clinically used antiepileptic drugs (AEDs) decrease membrane excitability by interacting with ion channels or neurotransmitter receptors. Currently available AEDs appear to act on sodium channels, GABA A receptors, or calcium channels. Phenytoin, carbamazepine, and possibly valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing sodium channel inactivation. Benzodiazepines and barbiturates enhance GABA A receptor-mediated inhibition. Ethosuximide and possibly VPA reduce a low-threshold calcium current. The mechanisms of action of AEDs currently under development are less clear. Lamotrigine may decrease sustained high-frequency repetitive firing. The mechanisms of action of felbamate are unknown. Gabapentin (GBP) appears to bind to a specific binding site in the central nervous system with a restricted regional distribution, but the identity of the binding site and the mechanism of action of GBP remain uncertain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66291/1/j.1528-1157.1993.tb05918.x.pd

Effects of non‐sedative anxiolytic drugs on responses to GABA and on diazepam‐induced enhancement of these responses on mouse neurones in cell culture

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92395/1/j.1476-5381.1988.tb16554.x.pd

Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture

Four guanidino compounds that have been found to be markedly increased in cerebrospinal fluid and brain tissue of uremic patients, namely, guanidine, methylguanidine, creatinine, and guanidinosuccinic acid, were applied to mouse spinal cord neurons in primary dissociated cell culture to evaluate their effects on postsynaptic responses to gammaaminobutyric acid (GABA) and glycine. Intracellular microelectrode recording techniques were used. Guanidine, methylguanidine, creatinine, and guanidinosuccinic acid reversibly and in a dose-dependent manner inhibited both GABA and glycine responses. Guanidinosuccinic acid was the most potent inhibitor of the amino acid responses, followed in decreasing potency by methylguanidine, guanidine, and creatinine. Guanidinosuccinic acid inhibited responses to GABA and glycine, at concentrations similar to those found in cerebrospinal fluid and brain tissue of patients with terminal renal insufficiency. The other guanidino compounds tested exerted their effects only at concentrations higher than those found in uremic biological fluids and tissues. The inhibitory effect of guanidine and methylguanidine on responses to GABA was additive. The effect of the guanidino compounds on GABA responses was not antagonized by coapplication of the benzodiazepine-receptor antagonist CGS 9896. The results suggest that guanidine, methylguanidine, creatinine, and guanidinosuccinic acid inhibited responses to the inhibitory neurotransmitters GABA and glycine by blocking the chloride channel. The observed action of the studied guanidino compounds might contribute to the pathogenesis of the complex neurological symptomatology encountered in uremia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50338/1/410280505_ftp.pd