Biodistribution and catabolism of 18F-labeled N-epsilon-fructoselysine as a model of Amadori products

Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-epsilon-fructoselysine is formed via this reaction between the epsilon-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-epsilon-fructoselysine at the alpha-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-epsilon-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.     

Cognitive abilities and functional capacity in older adults: results from the modified Scales of Independent Behavior-Revised

The relationship between cognitive and functional abilities was examined in a sample of community-dwelling older adults. Self and informant (e.g., spouse) reports of participants' functional status were obtained on the modified Scales of Independent Behavior-Revised (mSIB-R). Participants also completed measures of processing speed, episodic memory, executive functioning, and verbal ability. Results showed that the mSIB-R correlated positively with cognitive variables. Hierarchical regression analyses suggested that each mSIB-R factor is predicted by somewhat different cognitive variables, after adjusting for demographic, health, and motor variables. This report-based measure was as accurate as a performance-based measure in classifying cognitive groups. Informant social/cognitive engagement and self physical/environment engagement factors showed the most promise in this regard. The findings reveal links between cognitive and functional abilities in a sample with varying degrees of cognitive impairment.     

Intraindividual Variability in Physical and Emotional Functioning: Comparison of Adults With Traumatic Brain Injuries and Healthy Adults

Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.     

Cognitive Functioning and Everyday Problem Solving in Older Adults

The relationship between cognitive functioning and a performance-based measure of everyday problem-solving, the Everyday Problems Test (EPT), thought to index instrumental activities of daily living (IADL), was examined in 291 community-dwelling non-demented older adults. Performance on the EPT was found to vary according to age, cognitive status, and education. Hierarchical regression analyses revealed that, after adjusting for demographic and health variables, measures of cognitive functioning accounted for 23.6% of the variance in EPT performance. In particular, measures of global cognitive status, cognitive decline, speed of processing, executive functioning, episodic memory, and verbal ability were significant predictors of EPT performance. These findings suggest that cognitive functioning along with demographic variables are important determinants of everyday problem-solving.     

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A

Background The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus.
Aim We compared the number of Wood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate.
Study design Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA ( n = 21) or etretinate ( n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0–3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters.
Results After CyA treatment the PASI-score amounted to 24 ± 4%, after etretinate to 56 ± 6% of the initial values (mean ± SEM). One week after CyA treatment, esosinophils dropped from 190 ± 21 to 137 ± 16/μ ( P = 0.038, Wilcoxon test), after 10 weeks to 127 ± 18/μ ( P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 ± 1.30 (CyA) and 15.3 ± 5.53 μg/1 (etretinate) were measured (normal range 3–16 /μg/1), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional.
Outcome We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.     

Neurocognitive markers of cognitive impairment: exploring the roles of speed and inconsistency

A well-known challenge for research in the cognitive neuropsychology of aging is to distinguish between the deficits and changes associated with normal aging and those indicative of early cognitive impairment. In a series of 2 studies, the authors explored whether 2 neurocognitive markers, speed (mean level) and inconsistency (intraindividual variability), distinguished between age groups (64-73 and 74-90+ years) and cognitive status groups (nonimpaired, mildly impaired, and moderately impaired). Study 1 (n = 416) showed that both level and inconsistency distinguished between the age and 2 cognitive status (not impaired, mildly impaired) groups, with a modest tendency for inconsistency to predict group membership over and above mean level. Study 2 (n = 304) replicated these results but extended them because of the qualifying effects associated with the unique moderately impaired oldest group. Specifically, not only were the groups more firmly distinguished by both indicators of speed, but evidence for the differential contribution of performance inconsistency was stronger. Neurocognitive markers of speed and inconsistency may be leading indicators of emerging cognitive impairment.     

Intraindividual variability as an indicator of malingering in head injury.

The utility of various measures of malingering was evaluated using an analog design in which half the participants (composed of three groups: naive healthy people, professionals working with head-injured people, individuals who suffered a head injury but not currently in litigation) were asked to try their best and the remainder was asked to feign believable injury. Participants were assessed with the Reliable Digit Span (RDS) task, the Victoria Symptom Validity Test (VSVT), and the Computerized Dot Counting Test (CDCT) on three separate occasions in order to determine whether repeat administration of tests improves prediction. The results indicated that regardless of an individual's experience, consideration of both level of performance (particularly on forced-choice symptom validity tasks) and intraindividual variability holds considerable promise for the detection of malingering.     

Psychometric Investigation of the Modified Scales of Independent Behavior-Revised in an Elderly Sample

Psychometric analysis of a modified version of the Scales of Independent Behavior-Revised (mSIB-R) was done by obtaining self- and informant- (e.g., spouse) reports of participants' functioning. Both reports showed excellent reliability, but with lower scores on the informant-reports than on the self-reports. Factor analysis of the mSIB-R resulted in three factors: basic living skills, social/cognitive engagement, and physical/environmental engagement. However, the composition of the factors varied somewhat by report (self or informant). The basic living skills factor on both reports correlated with Lawton and Brody's IADL measure. Investigating the mSIB-R's utility in differentiating among five groups with mild cognitive impairment suggested that informants rated individuals with deficits in multiple cognitive domains (including memory) the lowest across all factors. Self-reports were dependent on the factor in question. These results support the usefulness of the mSIB-R with non-demented elderly adults.     

On the differentiation of memory beliefs from memory knowledge: the factor structure of the Metamemory in Adulthood Scale

This study was designed to test the hypothesis that there are multiple factors of metamemory present in the Metamemory in Adulthood (MIA) questionnaire. Data on seven MIA scales from six separate studies on memory/metamemory relationships (total N = 750) were combined to yield two half-samples for cross-validation purposes. The samples were partitioned into young, middle-aged, and old groups. A multiple group confirmatory factor analysis was then conducted on the data, using the first half sample to develop a model and the second half sample to validate it. Although the models did not fully cross-validate, both analyses indicated that there are at least two higher-order factors in the MIA. The first involves beliefs about self-efficacy in using memory. The second factor combines knowledge about memory and affect concerning memory (e.g., achievement motivation). The analyses also indicated that the factor loadings for the second factor, tentatively labelled Knowledge, were invariant across the three age groups, but that there were age differences in the Self-Efficacy Beliefs factor loadings. The differences were localized to age-related increases in the loadings for the MIA Change and Locus scales. The two factor solution has potential for resolving conflicting results in the literature regarding age differences in both metamemory and metamemory/memory performance relationships.