Plasma esterases and inflammation in ageing and frailty

OBJECTIVES: Esterases are enzymes of drug metabolism known to be reduced in frail older people and during acute illness. The mechanism for this is unknown. The aim of this study was to examine esterase activity and inflammation in ageing and frailty. METHODS: Thirty frail patients (mean age 84.9 years) dependent on continuing inpatient care, 40 patients of intermediate frailty attending Day Hospital (84.2 years), 40 fit older controls (82.7 years) and 30 young controls (23.3 years) were studied. Frailty indicators, plasma esterase activities and markers of inflammation were measured. RESULTS: With increasing patient frailty, C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) increased significantly and esterase activity, with the exception of aspirin esterase, fell significantly (p < 0.005). There were significant negative correlations between log-transformed IL-6 and acetylcholinesterase (r = -0.354, p < 0.01), butyrylcholinesterase (r = -0.392, p < 0.01) and benzoylcholinesterase activity (r = -0.241, p < 0.05) and significant negative correlations between TNF-alpha and acetylcholinesterase (r = -0.223, p < 0.01), butyrylcholinesterase (r = -0.279, p < 0.01) and benzoylcholinesterase activity (r = -0.253, p < 0.01). Aspirin esterase activity did not correlate with IL-6 or TNF- alpha. CONCLUSION: Frailty was associated with higher inflammatory markers and lower esterase activity. There was a weak but significant negative correlation between both IL-6 and TNF-alpha and the activity of three of four esterases. The negative correlation between esterase activity and inflammatory markers may have a causal basis, comparable to the inflammatory suppression of cytochrome P-450 enzymes.     

The effect of community-acquired pneumonia on plasma esterases in older people

INTRODUCTION: Pneumonia is a major cause of morbidity and mortality in older people. The poor outcome of older pneumonia patients despite treatment is still not understood. OBJECTIVE: The aim of this study was to examine the effect of community-acquired pneumonia on enzymes of drug metabolism in older people. METHODS: Fifteen patients (median age 67 years) with a clinical and radiological diagnosis of community-acquired pneumonia and 14 healthy volunteers matched for age and gender (median age 75 years) were recruited. Plasma activities of benzoylcholinesterase, butyrylcholinesterase, acetylcholinesterase and aspirin esterase were determined spectrophotometrically at three time points in pneumonia patients--within 24 h of admission to hospital, 2 days later and 10 days later. Monocyte aryl hydrocarbon hydroxylase (AHH) activity was determined spectrofluorimetrically at the same time points. Enzyme activities were measured at one time point in healthy controls. RESULTS: Mean plasma benzoylcholinesterase activity was significantly lower in pneumonia patients on admission to hospital (mean +/- SEM 848 +/- 100) and after 10 days of treatment (mean +/- SEM 925 +/- 114) than in healthy controls (mean +/- SEM 1333 +/- 84, P < 0.05). Similarly, plasma acetylcholinesterase activity was significantly lower in pneumonia patients on admission (P = 0.007) and after 10 days of treatment (P = 0.01) than in controls. Butyrylcholinesterase activity was lower in pneumonia patients on admission (P = 0.029) than in healthy controls, but improved slightly after treatment so there was no longer a significant difference at 10 days compared with controls (P = 0.077). In contrast there were no significant differences in plasma aspirin esterase activity or induced monocyte AHH activity between pneumonia patients and healthy controls. The activities of benzoylcholinesterase (r = -0.536, P = 0.04), butyrylcholinesterase (r = -0.638, P = 0.01), acetylcholinesterase (r = -0.583, P = 0.022) and aspirin esterase (r = -0.624, P = 0.013) correlated inversely with the British Thoracic Society pneumonia poor prognostic index. CONCLUSION: The activities of several esterases are reduced in older pneumonia patients. Other enzymes including aspirin esterase and induced monocyte AHH activity are unaltered in pneumonia. There was a significant inverse relationship between the activities of all esterases studied and the British Thoracic Society pneumonia poor prognostic index.     

The effect of age and frailty upon blood esterase activities and their response to dietary supplementation

1. The aims of this study were two-fold. First, to define ranges of blood esterase activities in three groups, namely young subjects, fit community dwelling elderly and frail, chronically hospitalised elderly subjects, and second, to determine whether low blood esterase activities in the frail patients could be altered by increasing their nutritional intake. 2. Plasma cholinesterase, aspirin esterase, paraoxonase and phenylacetate esterase activities were all significantly lower in the frail elderly compared with the young and fit elderly volunteers. The activity of red blood cell esterase was not different in the frail elderly. 3. Fourteen frail elderly patients were randomly assigned to receive either hospital meal provision plus supplemental feeding with Build-up (Nestle) and Maxijul (SHS Ltd) or hospital provision alone for 8 weeks. Dietary intake was measured for all patients at the start of the study and at week 8. Measurements of blood esterase (cholinesterase, phenylacetate esterase, paraoxonase, aspirin esterase and red blood cell esterase), albumin and anthropometric indices (weight, triceps skinfold thickness and mid arm circumference) were made before the study and repeated at week 4 and 8. 4. There was a significant increase in plasma cholinesterase at week 4 (P < 0.05) but this was not statistically significant at week 8. There were no significant changes in any of the other esterase activities or anthropometric measurements. 5. We conclude that the lower esterase activities of the frail chronically hospitalised elderly do not respond to dietary supplementation for a period of 8 weeks with routinely available products. The hypothesis that lower esterase activities are the direct result of undernutrition which would be corrected by dietary supplementation has not been supported by this study.     

Effect of age and nutritional status on heart rate responses to cough and maximum handgrip

Autonomic nerve activity can be assessed using simple bed side tests such as cough and maximum hand grip (MHG). The alterations in these tests are, however, poorly documented in physiological states. The present study aimed to uncover the effect of nutritional status and age on these tests. 93 male adults were divided into normal body mass index (BMI) (BMI; 18.5 to 25 kg/m2; young 18-30 yrs, n=28; old >60 yrs, n=25) and low BMI (BMI; <18.5 kg/m2; young 18-30 yrs, n=19; old >60 yrs, n=14) groups. The younger subjects showed a significantly higher heart rate response to cough and MHG in both normal and low BMI groups as compared to the older subjects (P<0.01). However, there were no significant differences for the heart rate responses to cough and MHG between the low and normal BMI groups either in the young or in the elderly. The data suggest that while the heart rate response to cough and MHG are useful tests of vagal activity to the heart when expected differences are large, they may be of limited use in uncovering more subtle changes.     

Clinical significance of esterases in man

Esterases, hydrolases which split ester bonds, hydrolyse a number of compounds used as drugs in humans. The enzymes involved are classified broadly as cholinesterases (including acetylcholinesterase), carboxylesterases, and arylesterases, but apart from acetylcholinesterase, their biological function is unknown. The acetylcholinesterase present in nerve endings involved in neurotransmission is inhibited by anticholinesterase drugs, e.g. neostigmine, and by organophosphorous compounds (mainly insecticides). Cholinesterases are primarily involved in drug hydrolysis in the plasma, arylesterases in the plasma and red blood cells, and carboxylesterases in the liver, gut and other tissues. The esterases exhibit specificities for certain substrates and inhibitors but a drug is often hydrolysed by more than one esterase at different sites. Aspirin (acetylsalicylic acid), for example, is hydrolysed to salicylate by carboxylesterases in the liver during the first-pass. Only 60% of an oral dose reaches the systemic circulation where it is hydrolysed by plasma cholinesterases and albumin and red blood cell arylesterases. Thus, the concentration of aspirin relative to salicylate in the circulation may be affected by individual variation in esterase levels and the relative roles of the different esterases, and this may influence the overall pharmacological effect. Other drugs have been less extensively investigated than aspirin and these include heroin (diacetylmorphine), suxamethonium (succinylcholine), clofibrate, carbimazole, procaine and other local anaesthetics. Ester prodrugs are widely used to improve absorption of drugs and in depot preparations. The active drug is released by hydrolysis by tissue carboxylesterases. Individual differences in esterase activity may be genetically determined, as is the case with atypical cholinesterases and the polymorphic distribution of serum paraoxonase and red blood cell esterase D. Disease states may also alter esterase activity.     

Reaction of human albumin with aspirin in vitro: Mass spectrometric identification of acetylated lysines 199, 402, 519, and 545

The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.     

Aspirin binding and the effect of albumin on spontaneous and enzyme-catalysed hydrolysis

A method of measuring the binding of aspirin to albumin without the interference of hydrolysis was developed. At concentrations of 10 mg litre^?1, aspirin is about 85% bound to bovine serum albumin (4 g%), whereas its hydrolysis product, salicylic acid, is 95% bound. Salicylic acid was shown to displace aspirin from albumin binding sites. Both salicylic acid and aspirin bind more strongly to bovine serum albumin than to human serum albumin at protein concentrations of 4 g%. Protein binding protected aspirin against spontaneous hydrolysis although protein-bound aspirin still hydrolysed at a finite rate. In contrast, albumin enhanced the enzyme-catalysed hydrolysis of aspirin. By using a simple model, the rate constants for the individual processes contributing to the overall hydrolysis rate constant in the presence of albumin and esterase are calculated.     

Age-related alteration of carbamazepine-serum protein binding in man.

To determine whether biological maturation influences the kinetics of carbamazepine-serum protein binding, the carbamazepine free fraction (%) was investigated in the serum of 66 patients, ranging from 4 to 83 years, with epilepsy or trigeminal neuralgia, treated with carbamazepine alone or carbamazepine in combination with phenytoin, phenobarbital, and/or valproic acid, over a relatively long period. Biochemical parameters such as levels of albumin and non-glycated albumin showed a significant relationship with carbamazepine free fraction (r = -0.521, P < 0.001 for albumin; r = -0.700, P < 0.001 for non-glycated albumin). Non-glycated albumin was more strongly correlated with carbamazepine free fraction. The biochemical parameters showed a significant relationship with age (r =-0.243, P < 0.1 for albumin; r =0.666, P < 0.001 for glycated albumin; r = -0.459, P < 0.001 for non-glycated albumin; r = 0.640, P < 0.001 for carbamazepine free fraction). Glycated albumin (%), non-glycated albumin and carbamazepine free fraction (%) were strongly correlated with age, whereas albumin showed only a weak correlation with age. To evaluate the effects of ageing on carbamazepine-serum protein binding, the patients were divided into three groups according to age: children, 4-15 years; adults, 16-64 years; elderly, 65-83 years. Albumin and non-glycated albumin were much lower, and glycated albumin (%) and carbamazepine free fraction (%) much higher in the elderly group than in the other two groups. The results of this study showed that the major ligand of carbamazepine in the serum was non-glycated albumin, which decreased with age. These observations suggested that in elderly patients, the elevation of free carbamazepine concentrations in the serum caused by reduced non-glycated albumin levels, induces increases in the sensitivity of the pharmacological effects of carbamazepine and the risk of drug interactions.     

C-反应蛋白水平与维持性血液透析老年患者营养状态及贫血的关系

目的评价老年维持性血液透析患者C-反应蛋白（CRP）与营养状态及贫血的关系。方法38例老年及同期42例年轻维持性血液透析患者于透析日空腹采血测定红细胞（RBC）、血红蛋白（Hb）、红细胞压积（Hct）、转铁蛋白（TF）以及血浆白蛋白（Alb）、血肌酐（SCr）、尿素氮（BUN）和CLIP;测定患者肱三头肌皮褶厚度（TSF）、上臂围（AC）、上臂肌围（AMC）等。结果老年维持性血液透析患者TSF、AC、AMC、RBC、Hsb、Hct、TF、BUN、SCr、Alb均显著低于年轻组患者,而CRP水平显著高于年轻组患者（P〈0．05或P〈0．01）;老年患者CRP与Hsb、Hct、Alb呈显著负相关（P〈0．01,P〈0．01,P〈0．05）。结论CRP是反映维持性血液透析患者早期营养不良及炎性反应的敏感指标。     

Salicylate protein binding in serum from young and elderly subjects as measured by diafiltration

Summary The protein binding of salicylate was measured by continuous ultrafiltration (diafiltration) at 22°C in serum obtained from 5 healthy young (mean age: 27 years) and 5 healthy elderly (mean age: 73 years) male volunteers. Unbound salicylate increased disproportionately with increasing total salicylate concentration, up to 7000 µmol, in all sera. The fraction bound of salicylate was significantly lower in sera from elderly but this was not due to decreased albumin or total protein concentrations. The binding of salicylate to serum proteins was characterized by two classes of binding sites. The high affinity site had an association constant of either 94901/mol (young) or 75601/mol (elderly) and the number of binding sites was either 4.7 (young) or 3.7 (elderly). The total binding capacity of the low affinity site, 1121/mol, in sera from elderly was significantly less than the binding capacity, 631l/mol, in sera from young. Differences in binding capacity of the low affinity site partially accounted for a two to three-fold increase in the salicylate free fraction in elderly sera. These data suggest that age-related differences in serum protein binding may influence salicylate pharmacokinetics.     

The pharmacokinetics of frusemide are influenced by age.

After a 24 h control period 80 mg frusemide was given intravenously over 2 min to a group of young and a group of elderly healthy male volunteers. The serum concentration of frusemide and the excretion in urine of the drug and a glucuronidated metabolite were followed for 24 h. The elimination of the drug from serum was described by an open two compartment model. The serum clearance (CLs) was 170 +/- 19 ml min-1 in the young and 129 +/- 11 ml min-1 in the elderly (P less than 0.01) and the average renal clearance (CLr) was 67% of CLs in the young and 58% of CLs in the elderly (NS). The average amount of unchanged frusemide in the urine during the first 30 min was 30 +/- 6 mg in the young but only 20 +/- 4 mg in the elderly (P less than 0.01). The albumin concentration in serum was 15% lower in the elderly but on the average the protein bound fraction of frusemide was 98.6% in both groups. The Vd ss did not differ between the two age groups (0.130 1 kg-1) but the elimination half-life was 70 +/- 20 min in the young and 102 +/- 33 min in the elderly (P less than 0.05). In the young 11.4 +/- 5.0 mg frusemide was excreted as a glucuronidated compound whereas this figure was only 5.4 +/- 2.9 mg in the elderly (P less than 0.01). It is concluded that the age-related changes in the fate of unchanged frusemide in the organism mainly can be explained by a reduction in the tubular secretion of the drug which in turn may be caused by a reduction in renal plasma flow.     

Measurement of human urinary kallikrein and evidence for non-kallikrein urinary TAMe esterases by direct immunoassay and by affinity chromatography

Kallikrein was separated from other $\text{p-}\text{tosyl-}\text{L}\text{-arginine}$ methyl ester (TAMe) esterases in human urine by direct affinity chromatography of concentrated fresh pooled urine. Quantitative analysis of total TAMe esterase activity in pooled, fractionated urine indicated that less than one-third was due to urokallikrein and that the remainder was attributable to one or more esterases which lack kinin-generating activity and fail to react with a monospecific anti-urokallikrein serum. Using a radial immunodiffusion assay for human urokallikrein, recovery of purified urokallikrein added to urine was 95 per cent and the coefficient of variation in replicate analyses was 8.4 per cent. When this method was compared with a kinin-generating and a [³H]TAMe esterase method for determination of kallikrein activity in urine, all three assays were well correlated in 50 urine samples from normal subjects in varying states of salt and water metabolism. However, analysis of the regression line of esterase activity on antigen concentration indicated that at least half of the urinary TAMe esterase activity was due to non-kallikrein esterases. The demonstration by direct assay and by separation techniques that at least one-half of the alkaline TAMe esterase activity of urine is not urokallikrein indicates that changes in urinary esterase activity cannot be equated solely with alterations in urokallikrein. A combination of direct immunological and kinin-generating assays should permit accurate evaluation of urokallikrein concentration and activity.     

Clinical pharmacokinetics of the salicylates

The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral administration as an aqueous solution aspirin is rapidly absorbed at the low pH of the stomach millieu. Less rapid absorption is observed with other formulations due to the rate limiting step of tablet disintegration - this latter factor being maximal in alkaline pH. The rate of aspirin absorption is dependent not only on the formulation but also on the rate of gastric emptying. Aspirin absorption follows first-order kinetics with an absorption half-life ranging from 5 to 16 minutes. Hydrolysis of aspirin to salicylic acid by nonspecific esterases occurs in the liver and, to a lesser extent, the stomach so that only 68% of the dose reaches the systemic circulation as aspirin. Both aspirin and salicylic acid are bound to serum albumin (aspirin being capable of irreversibly acetylating many proteins), and both are distributed in the synovial cavity, central nervous system, and saliva. The serum half-life of aspirin is approximately 20 minutes. The fall in aspirin concentration is associated with a rapid rise in salicylic acid concentration. Salicylic acid is renally excreted in part unchanged and the rate of elimination is influenced by urinary pH, the presence of organic acids, and the urinary flow rate. Metabolism of salicylic acid occurs through glucuronide formation (to produce salicyluric acid), and salicyl phenolic glucoronide), conjugation with glycine (to produce salicyluric acid), and oxidation to gentisic acid. The rate of formation of salicyl phenolic glucuronide and salicyluric acid are easily saturated at low salicylic acid concentrations and their formation is described by Michaelis-Menten kinetics. The other metabolic products follow first-order kinetics. The serum half-life of salicylic acid is dose-dependent; thus, the larger the dose employed, the longer it will take to reach steady-state. There is also evidence that enzyme induction of salicyluric acid formation occurs. No significant differences exist between the pharmacokinetics of the salicylates in the elderly or in children when compared with young adults. Apart from differences in free versus albumin-bound salicylate in various disease states and physiological conditions associated with low serum albumin, pharmacokinetic parameters in patients with rheumatoid arthritis, osteoarthritis, chronic renal failure or liver disease are essentially the same.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative efficacy of soluble aspirin and aspirin tablets in postoperative dental pain

Summary The efficacy of single doses (1.2 g) of soluble aspirin and aspirin tablets was determined in a randomised, placebo-controlled, double-blind, parallel study in 90 patients (45 females) with postoperative pain after removal of impacted lower third molars. Also investigated was the relationship between plasma aspirin esterase activity and overall pain scores after both aspirin preparations. Patients reported significantly less pain (p<0.001) after treatment with aspirin than after treatment with placebo. However, patients receiving soluble aspirin reported both an earlier onset and a longer duration of pain relief than those who received aspirin tablets. A significant correlation was observed between plasma aspirin esterase activity and overall pain scores after both soluble aspirin (r=0.57,p<0.01) and aspirin tablets (r=0.51,p<0.02). It is concluded that soluble aspirin is the preferred aspirin formulation for treating postoperative pain after third molar surgery and that plasma aspirin esterase activity is a determinant of a patient's analgesic response to aspirin in postoperative dental pain.     

“A” esterases and their role in regulating the toxicity of organophosphates

Esterases which can hydrolyse organophosphates without being inhibited by them are termed A esterases. Using paraoxon and pirimiphos-methyl oxon as substrates, high A esterase activity is found in the liver and plasma or serum of a range of mammalian species. In a study of serum A esterases of sheep and humans, over 80% of the activity separated into the high density lipoprotein (HDL) fraction following ultracentrifugation. When HDL fractions from sheep serum were run on Sepharose gel columns, most of the paraoxonase activity separated as a single peak of estimated molecular weight 360000, which corresponds to that of HDL₂ of humans.During the course of purification of A esterases by three different column procedures, contrasting esterase elution profiles were obtained with organophosphate and pyrethroid substrates. This was strong evidence for the existence of multiple forms of HDL A esterases.Levels of A esterase activity in plasma and liver of birds were much lower than those of mammals. This appears to be the main reason why birds are much more susceptible than mammals to organophosphates such as pirimiphos-methyl and diazinon which form active oxons that are good substrates for mammalian A esterases.No A esterase was detected in strains of rust red flour beetle (Tribolium castaneum) which were resistant to organophosphates. Similar observations have been made with strains of other insects resistant to organophosphates, raising the question to what extent esterases of this type are present in insects.Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday     

Aspirin binding and the effect of albumin on spontaneous and enzyme-catalysed hydrolysis

A method of measuring the binding of aspirin to albumin without the interference of hydrolysis was developed. At concentrations of 10 mg litre-1, aspirin is about 85% bound to bovine serum albumin (4 g %), whereas its hydrolysis product, salicylic acid, is 95% bound. Salicylic acid was shown to displace aspirin from albumin binding sites. Both salicylic acid and aspirin bind more strongly to bovine serum albumin than to human serum albumin at protein concentrations of 4 g %. Protein binding protected aspirin against spontaneous hydrolysis although protein-bound aspirin still hydrolysed at a finite rate. In contrast, albumin enhanced the enzyme-catalysed hydrolysis of aspirin. By using a simple model, the rate constants for the individual processes contributing to the overall hydrolysis rate constant in the presence of albumin and esterase are calculated.     

Novel nonsteroidal antiinflammatory drugs possessing a nitric oxide donor diazen-1-ium-1,2-diolate moiety: design, synthesis, biological evaluation, and nitric oxide release studies

A novel group of hybrid nitric oxide-releasing nonsteroidal antiinflammatory drugs ((*)NO-NSAIDs) possessing a 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (11, 13, 15) or 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (12, 14, 16) moiety attached via a one-carbon methylene spacer to the carboxylic acid group of the traditional NSAIDs aspirin, ibuprofen, and indomethacin were synthesized. Although none of these ester prodrugs (11-16) exhibited in vitro cyclooxygenase (COX) inhibitory activity against the COX-1 and COX-2 isozymes (IC(50) > 100 microM), all of the compounds (11-16) significantly decreased carrageenan-induced rat paw edema. In this regard, the ester prodrugs 11-16 showed equipotent antiinflammatory activities in vivo to that of the parent drugs aspirin, ibuprofen, and indomethacin. All of the compounds released nitric oxide upon incubation with either phosphate buffer solution at pH 7.4 (14-16% range) or porcine liver esterase (16-19% range), but the percentage of (*)NO released was up to sixfold higher (93%) when these ester prodrugs were incubated with guinea pig serum. These incubation studies suggest that both (*)NO and the parent NSAID would be released upon in vivo cleavage by nonspecific serum esterases. The simultaneous release of aspirin and nitric oxide from the (*)NO-aspirin prodrugs constitutes a potentially beneficial property for the prophylactic prevention of thrombus formation and adverse cardiovascular events such as stroke and myocardial infarction. The data acquired in an in vivo ulcer index (UI) assay showed that for this group of ester prodrugs, particularly the (*)NO-aspirins (11, 12) and (*)NO-ibuprofens (13, 14), no lesions were observed (UI = 0) when compared to the parent drugs aspirin (UI = 57, 250 mg/kg po dose), ibuprofen (UI = 45, 250 mg/kg po dose), or indomethacin (UI = 34, 30 mg/kg po dose) at equivalent doses. Accordingly, these hybrid (*)NO-NSAID prodrugs possessing a diazen-1-ium-1,2-diolate moiety, represent a new approach for the rational design of antiinflammatory drugs with reduced gastric ulcerogenicity.     

The prevalence of malnutrition in elderly hip fracture patients

AIM: To determine the prevalence of protein and energy malnutrition in elderly patients with a fracture of the proximal femur, in New Zealand. METHODS: Consecutive elderly patients (65 years and over) admitted to Christchurch Hospital with a fracture of the proximal femur over a four-month period were recruited. Nutritional indices were measured within three days of admission. These included triceps skinfold thicknesses, mid upper arm circumference, serum albumin and pre-albumin. RESULTS: Forty-two per cent of patients had at least two, and nine per cent had three, indicators of protein and energy malnutrition present on admission. There was no significant difference in the prevalence of malnutrition between young old (<80 years) and old old (80 years and over) patients. Patients residing in an institution had lower mean protein reserves, as indicated by lower corrected arm muscle area (p=0.003) and pre-albumin levels (p=0.09), than those living in the community. A drink, rather than a pudding or biscuit, was the preferred protein and energy supplement form. Ensure Plus (lactose-free) and Fortisip (lactose-free) were the most preferred drink supplements. CONCLUSION: Protein and energy malnutrition is common in elderly New Zealanders who fracture their femur. The prevalence is comparable to overseas data. These patients prefer nutritional supplementation given as a drink.     

老年和青年2型糖尿病不同发病年龄与血清脂联素的关系

目的以不同发病年龄阶段的新发2型糖尿病患者为研究对象,研究血清脂联素浓度差别及其作用。方法根据1999年WHO与国际糖尿病联合会糖尿病诊断标准入选2004～2006年新诊断的2型糖尿病患者120例。入选者按性别和年龄分组（〉60岁61例为老年糖尿病组,〈40岁59例为青年糖尿病组）,另选择老年和青年对照组各60例。分析各组影响血清脂联素水平的因素。结果糖尿病各组血清脂联素水平低于对照组[老年男性（2．27±1．77）mg／Lvs（3．97±1．49）mg／L,老年女性（2．76±1．29）mg／LVS（4．44±1．89）mg／L,青年男性（1．15±0．92）mg／LVS（3．23±1．28）mg／L,青年女性（2．92±2．15）mg／LVS（5．94±1．57）mg／L]（P〈0．01）。血清脂联素与性别相关,女性高于男性（P〈0．01）,并与体重指数和腰围呈负相关（P〈0．01）。控制性别、体质指数、腰围后与其他指标无明显相关性（P〉0．05）。青年糖尿病组与对照组相比血清脂联素下降水平高于老年组下降水平（P〈0．01）,女性更明显。结论青年2型糖尿病患者与对照组间的脂肪、能量代谢变化差异比老年更明显。     

A comparative study of the effects of aspirin and paracetamol (acetaminophen) on platelet aggregation and bleeding time

Summary In a double blind, randomised trial, the effects of 1 g aspirin and 1 g paracetamol were compared on bleeding time and platelet aggregation in 40 volunteers (20 females). Also investigated was the relationship between plasma aspirin esterase activity and both bleeding time and platelet aggregation after aspirin. Following 1 g aspirin there was a significant increase in bleeding time at 24 h (p<0.01). A significant reduction (P<0.01) in platelet aggregation with collagen was observed at 1, 6 and 24 h after aspirin, but no significant reduction (P>0.05) was observed with ADP. Paracetamol had no effect on bleeding time or platelet aggregation. Plasma aspirin esterase activity ranged from 0.26–0.6 µmol/ml/min. A significant negative correlation (R=–0.55, P<0.001) was observed between percentage increase in bleeding time (24 h) and plasma aspirin esterase activity. Further significant correlations were observed between plasma aspirin esterase activity and change in platelet aggregation with collagen at 1 h (R=0.68, P<0.001), 6 h (R=–0.73, P<0.001) and 24 h (R=–0.67, P<0.001). These results suggest that it might be possible to predict an individual's haemostatic response to aspirin from knowledge of their plasma aspirin esterase activity.