Plasma esterases and inflammation in ageing and frailty

Hubbard, Ruth E.; O'Mahony, M Sinead; Calver, Brian L.; Woodhouse, Ken

doi:10.1007/s00228-008-0499-1

Cited by 121 publications

(78 citation statements)

References 32 publications

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“…This result was in line with previous findings in F344 rats (Kosasa et al, 1999). In elderly subjects, the plasma BChE activity was enhanced although AChE activity was maintained (Hubbard et al, 2008). Upon dosing with the ChEIs, donepezil exerted the greatest inhibitory effect on total ChE, derived mostly from AChE inhibition.…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats

Goh¹,

Aw²,

Lee³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Physiological alterations that may change pharmacological response accompany aging. Pharmacokinetic/pharmacodynamic properties of cholinesterase inhibitors (ChEIs) used in the treatment of Alzheimer's disease, donepezil, tacrine, and galantamine, were investigated in an aged Lister hooded rat model. Intravenous and oral 6-h blood sampling profiles in old (30 months old) and young (7 months old) rats revealed pharmacokinetic changes similar to those in humans with an approximately 40% increase in C max of galantamine and prolonged t 1/2 (1.4-fold) and mean residence time (1.5-fold) of donepezil. Tacrine disposition was maintained with age, and area under the concentration-time curve and clearance in old rats were similar to those in young rats for all drugs tested as was bioavailability. Old rats showed a trend of increased pharmacodynamic sensitivity (<20%) to ChEIs in cholinesterase activity assays, which was attributed to pharmacokinetic effects because a trend of higher blood and brain concentrations was seen in the old rats although brain/blood ratios remained unaffected. Enhanced cholinergic-mediated behaviors such as tremor, hypothermia, salivation, and lacrimation were also observed in the old rats, which could not be accounted for by a similar magnitude of change in pharmacokinetics. A decrease in expression of muscarinic acetylcholine receptor subtype 2 detected in old rat brains was postulated to play a role. Greater age effects in both pharmacokinetics and pharmacodynamics of donepezil and tacrine were seen in previous studies with Fischer 344 rats, indicating a potential risk in overreliance on this rat strain for aging studies.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats

Goh¹,

Aw²,

Lee³

et al. 2010

Drug Metab Dispos

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“…Esterases are phase I enzymes of drug metabolism found widely in tissues and plasma, the liver being the most important site of synthesis. They are reduced in frail older people but not affected by ''healthy ageing'' (Williams et al 1989), with a weak but significant negative correlation between inflammatory markers and esterase activity (Hubbard et al 2008). This may have a causal basis, comparable to the inflammatory suppression of cytochrome P-450 (CYP) enzymes.…”

Section: Clinical Relevancementioning

confidence: 96%

Frailty, inflammation and the elderly

2010

Self Cite

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Frailty is a term used as a marker of vulnerability, identifying individuals with a diminished capacity to respond to external stressors. Those who are frail are at increased risk of death, institutionalisation and worsening disability. While the associations of frailty with increasing chronological age, female gender, functional dependence and chronic disease are now well described, the aetiology of frailty remains less clearly understood. The growing body of evidence linking inflammation and frailty in older people, an association that seems consistent across different frailty definitions, is therefore of great interest to research gerontologists. However, further studies are needed to establish the exact nature of this relationship. Inflammation may be primarily causal, a compensatory response to viral antigens or subclinical disease or an epi-phenomenon, merely a marker of another key pathophysiological process such as excessive oxidative stress. Furthermore, it has recently been recognised that frailty is most strongly associated with a combination of immunological and physiological impairments rather than a single biomarker. This supports the conceptualisation of ageing as the progressive accumulation of damage to a complex system resulting in aggregate loss of system redundancy. The frail older person is analogous to a complex system without redundancy: capacity to respond to external stressors is reduced. A critical mass of abnormalities across different systems may therefore be a more important determinant of frailty than any individual pathway.

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“…In addition, plasma choline esterase activity in advanced rheumatoid arthritis was found to be lower than in less advanced cases (29). In an earlier study conducted on a geriatric population, negative correlations of IL-6 and TNF-α with choline esterases were reported (30). In the same study, frailty was also associated with high inflammatory markers and low choline esterase activities (30).…”

Section: Türk Fizmentioning

confidence: 86%

“…In an earlier study conducted on a geriatric population, negative correlations of IL-6 and TNF-α with choline esterases were reported (30). In the same study, frailty was also associated with high inflammatory markers and low choline esterase activities (30).…”

Section: Türk Fizmentioning

confidence: 91%

Ailesel Akdeniz Ateşli Hastalarda Kolinesteraz, Adenozin Deaminaz ve Miyeloperoksidaz Aktiviteleri

Özkol¹,

Ediz²,

Şekeroğlu³

et al. 2012

tftr

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Objective: The aim of this study was to determine Acetylcholinesterase (AChE), Butyrilcholinesterase (BChE), Adenosine Deaminase (ADA) and Myeloperoxidase (MPO) activities in patients with Familial Mediterranean Fever (FMF) during attacks and attack-free periods. Although an inflammatory process is the main pathology in FMF, the activities of AChE, BChE and MPO which might be affected by inflammation has not yet been assessed in FMF. Materials and Methods: The subjects were divided into 3 groups: Group 1. FMF patients in acute attack period (FMF-AP); Group 2. FMF patients in attack-free period (FMF-AFP); Group 3. Healthy Control subjects (HC). The first two groups consisted of 41 and 35 patients, respectively. Thirty individuals without a history of other potential health problems constituted the healthy control (HC) group. We measured the activities of MPO, ADA, AChE and BChE in whole blood and serum of the study groups. Acute phase reactants (AFP) were also evaluated. Results: In the current study, while ADA and MPO activities increased, AChE decreased significantly in both whole blood and serum in FMF-AP group, BChE decreased in only whole blood in this group compared with FMF-AFP and HC groups (p<0.05). In FMF-AP group, both whole blood and serum ADA (r=0.313, r=0.267), and MPO (r=0.341, r=0.253) activities were correlated with C-reactive protein, respectively (all p values <0.001). Conclusion: Our study demonstrated that there are significant differences between FMF-AP and other groups in terms of AChE, BChE, ADA and MPO activities. Thus, we suggest that elevated ADA, MPO and decreased AChE and BChE activities may be considered as supportive markers to distinguish FMF attacks from attack-free periods. However, further larger-scale studies are needed to validate these results.

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Plasma esterases and inflammation in ageing and frailty

Cited by 121 publications

References 32 publications

Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats

Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats

Frailty, inflammation and the elderly

Ailesel Akdeniz Ateşli Hastalarda Kolinesteraz, Adenozin Deaminaz ve Miyeloperoksidaz Aktiviteleri

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