bluuebunny/crossref_metadata_2025 huggingface dataset:
Do caregivers' experiences correspond with the concerns raised in the literature? Ethical issues relating to anti‐dementia drugs
Authors: Huizing Anna R. , Berghmans Ron L.P. , Widdershoven Guy A.M. , Verhey Frans R.J.
Published: September 2006

Background

The use of Cholinesterase inhibitors (ChE‐Is) has raised debate in the literature on the ethical issues of drug treatment in dementia patients. These issues concern the quality of life of dementia patients and the process of decision‐making regarding the use of ChE‐Is. We interviewed caregivers of patients with dementia, focussing on issues of quality of life and the process of decision‐making regarding the use of anti‐dementia drugs.

Aim

The aim of this article is to explore whether the ethical concerns raised in the literature are actually in line with experiences in the daily practice of dementia care.

Methods

Qualitative data that have been collected by semi‐structured interviews with 12 caregivers of patients who (had) used ChE‐Is.

Results

The results seem to indicate that theoretical considerations should be modified in the light of the reported experiences of caregivers. For example, problematic consequences of an early diagnosis and the creation of unreasonable hope did not appear in the study. Also problems concerning the rising awareness of cognitive decline were not found.

Conclusion

In the interest of an ongoing ethical debate on the development and use of anti‐dementia drugs it is important to further specify theoretical issues and to conduct empirical research into the practice of decision making and to get more insight in the perspectives of the patients using anti‐dementia medicines themselves. Copyright © 2006 John Wiley & Sons, Ltd.
A cross‐sectional study on the health related quality of life of depressed Chinese older people in Shanghai
Authors: Chan Sally Wai‐chi , Shoumei J. I. A. , Thompson David R. , Yan H. U. , Chiu Helen F. K. , Chien Wai‐tong , Lam Linda
Published: September 2006

Background

With an increasing life expectancy, there is a rapidly growing sector that is aging. Depression is the most prevalent functional mental disorder of older population. It is estimated that about 21% of the older population in Shanghai are suffering from depression.

Aim

This study investigated the self‐rated health related quality of life of community‐dwelling older people diagnosed with depression in Shanghai, and to examine the relationships between this and mental and physical health, functional status and social support.

Methods

A cross‐sectional survey was conducted in two community centres with a convenience sample of 71 participants. Measures included subjective perception of health related quality of life, level of depression, cognitive function, number of medical conditions, activities of daily living, functional abilities, and social support. The majority of the participants were female (n = 52, 73.23%), and married (n = 51, 71.8%).

Results

A higher level of depression was related to a poorer health related quality of life. Participants were least satisfied with their physical health. The level of depression, activities of daily living and satisfaction with social support were predictors of health related quality of life ratings.

Conclusion

The study identified how depression affects the bio‐psychosocial status of Chinese older people. Findings are discussed in light of the socio‐cultural environment in Shanghai. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of a qigong exercise programme on elderly with depression
Authors: Tsang Hector W. H. , Fung Kelvin M. T. , Chan Ashley S. M. , Lee Grace , Chan Fong
Published: September 2006

Objectives

This report released findings of a randomized controlled trial conducted in Hong Kong to further our understanding of the psychosocial effects of qigong on elderly persons with depression.

Design

Eighty‐two participants with a diagnosis of depression or obvious features of depression were recruited and randomly assigned into the intervention and comparison group. The intervention group was given a 16‐week period of Qigong practice while the comparison group participated in a newspaper reading group with same duration and frequency.

Results

After eight weeks of qigong practice, the intervention group participants outstripped themselves in improvement in mood, self‐efficacy and personal well being, and physical and social domains of self‐concept when compared with comparison subjects. After 16 weeks of practice, the improvement generalized to the daily task domain of the self‐concept.

Conclusions

This report shows that regular qigong practice could relieve depression, improve self‐efficacy and personal well being among elderly persons with chronic physical illness and depression. Copyright © 2006 John Wiley & Sons, Ltd.
Mirtazapine orally disintegrating tablets in depressed nursing home residents 85 years of age and older
Authors: Nelson J. Craig , Hollander Steven B. , Betzel James , Smolen Philip
Published: September 2006

Introduction

Treatment studies of depression in the very oldest patients are infrequent. For these reasons, this study of mirtazapine orally disintegrating tablets was carried out in nursing home residents ≥85 years old with physician‐diagnosed depression. The naturalistic conditions of the study allowed us to include patients with cognitive impairment, concomitant medications and comorbid illness.

Methods

This was a subgroup analysis of nursing home residents ≥85 years old who took part in a larger 12‐week open‐label trial. Patients were eligible if they had physician‐diagnosed depression, and a Mini‐Mental State Exam score ≥10. The physician or nurse coordinator obtained data from healthcare professionals in daily contact with the patient to complete the Clinical Global Impression (CGI) scale, a modified 16‐item Hamilton Depression Scale (HAM‐D), and the Cornell Scale for Depression in Dementia (CSDD). Treatment‐emergent adverse events were recorded.

Results

Of the 50 patients enrolled at 23 sites, 72% completed the 12‐week trial. The mean age of the participants was 89.3 years. The mean HAM‐D score declined from 16.9 at baseline to 7.3 at endpoint (ITT, LOCF analysis) For the CSDD, the mean score declined from 15.1 to 7.1. The percentage of responders on the CGI‐Improvement (CGI‐I) scale increased at each assessment reaching 55% at endpoint. Only 10% of the patients discontinued treatment because of adverse events. There was a mean increase in weight of 1.32 lbs (0.6 kg) at day 84.

Conclusion

Although lacking a placebo control, this naturalistic study suggests that mirtazapine orally disintegrating tablets were effective and well tolerated in this sample of depressed nursing home residents ≥85 years of age. Copyright © 2006 John Wiley & Sons, Ltd.
The assessment of fitness to drive in people with dementia
Authors: Lincoln Nadina B. , Radford Kate A. , Lee Elizabeth , Reay Alice C.
Published: September 2006

Objective

To determine whether cognitive tests predict fitness to drive in patients with dementia.

Design

Two group comparison of patients with dementia and healthy elderly volunteers, and comparison of patients with dementia who were found safe to drive and those found unsafe, followed by a validation study.

Participants

Forty‐two people with dementia and 33 healthy elderly volunteers with no known memory problems who were driving. Of the 42 people with dementia 37 were assessed on the road. A second sample of 17 people with dementia was also assessed on the road.

Main Measures

Stroke Drivers Screening Assessment, Mini Mental State Examination, Salford Objective Recognition Test, Stroop Test, Test of Everyday Attention, Visual Object and Space Perception Battery, Behavioural Assessment of the Dysexecutive Syndrome, Adult Memory and Information Processing Battery.

Results

All healthy elderly volunteers were safe to drive but 10 of the 27 patients with dementia were unsafe. Discriminant function analysis identified a combination of tests, which correctly classified 92% of drivers with dementia as safe or unsafe. Validation of this prediction on an independent sample had 59% accuracy using a cut‐off of 0 but 88% accuracy using a cut‐off of 5.

Conclusions

Safety to drive in people with dementia could be predicted from a combination of six cognitive tests. These correctly identified 67% of safe drivers in a validation sample. This assessment could be used to identify those who need evaluation of their safety on the road. Copyright © 2006 John Wiley & Sons, Ltd.
Psychological treatment of late‐life depression: a meta‐analysis of randomized controlled trials
Authors: Cuijpers Pim , van Straten Annemieke , Smit Filip
Published: September 2006

Background

Older meta‐analyses of the effects of psychological treatments for depression in older adults have found that these treatments have large effects. However, these earlier meta‐analyses also included non‐randomized studies, and did not include newer high‐quality randomized controlled trials.

Methods

We conducted a meta‐analysis of randomized studies on psychological treatments for depression in older adults.

Results

Twenty‐five studies were included, of which 17 compared a psychological intervention to a control condition (mainly waiting list and care‐as‐usual control groups). The quality of the included studies varied. Psychological treatments have moderate to large effects on depression in older adults (standardized mean effect size d = 0.72). Heterogeneity was very low. No differences were found between individual, group or bibliotherapy format, or between cognitive behavioral therapy and other types of psychological treatment. The effects were comparable in studies where depression was defined according to diagnostic criteria, and those in which depression was measured with self‐rating questionnaires.

Conclusion

Although the quality of many studies was not optimal, the results of this meta‐analysis support the results of earlier meta‐analyses, which also included non‐randomized studies. Psychological treatments are effective in the treatment of depression in older adults. Copyright © 2006 John Wiley & Sons, Ltd.
Co‐morbid and socio‐demographic factors associated with cognitive performance in an elderly community dwelling Irish population
Authors: Chin Ai‐Vyrn , O'Connell Henry , Kirby Michael , Denihan Aisling , Bruce Irene , Walsh J. B. , Coakley David , Lawlor Brian A. , Cunningham Conal
Published: September 2006

Background

Epidemiological studies suggest an association between health factors and dementia. The impact of these factors on the cognitive performance of the elderly population is unclear. Possible correlates of poor cognitive performance in a community dwelling elderly Irish population were examined.

Methods

Subjects were from a sample of individuals over 65 years agreeable to interview using the Geriatric Mental State (GMS)‐Automated Geriatric Examination for Computed Assisted Taxonomy (AGECAT) package conducted at the subject's home. Associations between patient profiles and Mini Mental State Examination (MMSE) score were investigated in a multivariate model.

Results

There were 793 subjects, 528 (66.6%) female with mean (s.d.) age 74.8 (6.7) yrs. Mean MMSE score was 26.5 (3.3). 169 (21.3%) were current smokers, 198 (25%) ex‐smokers. Two hundred and twenty‐four (28.3%) had a history of hypertension, 85 (10.7%) case level anxiety or depression, 51 (6.4%) stroke, ten0 (1.3%) epilepsy, nine (1.1%) Parkinson's disease and 29 (3.7%) dementia. Two hundred and fifty‐five (32.2%) subjects were on psychotropic medications. Factors associated with MMSE score included age (p ≤ 0.0001), diagnosis of dementia (p ≤ 0.0001), socioeconomic group (p ≤ 0.0001), education (p ≤ 0.0001), previous stroke (p = 0.0013) and use of psychotropic medication (p = 0.03). Case level anxiety or depression (p = 0.99), Parkinson's disease (p = 0.52), epilepsy (p = 0.26), smoking status (p = 0.99) and hypertension (p = 0.34) were not found to be associated with cognitive performance.

Conclusion

Factors associated with cognitive performance included age, socioeconomic group, education, previous stroke and use of psychotropic medication. These factors should be adjusted for in studies assessing cognition in this population. Stroke prevention strategies and avoidance of psychotropic medication may benefit cognitive performance. Copyright © 2006 John Wiley & Sons, Ltd.
Early diagnosis of dementia in primary care: a representative eight‐year follow‐up study in Lower Saxony, Germany
Authors: Maeck Lienhard , Haak Sebastian , Knoblauch Anita , Stoppe Gabriela
Published: September 2006

Objective

To investigate whether primary care competency in early diagnosis of dementia might have changed during 1993 and 2001.

Method

By means of a representative follow‐up survey 122 out of 170 (71.8%) family physicians (FPs) in Lower Saxony, Germany, were randomly assigned to two written case samples presenting a patient with mild cognitive impairment (case 1a vs. 1b: female vs. male patient) and moderate dementia (case 2a vs 2b: vascular type (VD) vs Alzheimer's disease (DAT)), respectively. By means of a structured face‐to‐face interview, they were asked for their diagnostic considerations.

Results

In comparison to 1993, dementia was significantly more frequently considered. However, there was a striking tendency in overestimating vascular aetiology and under‐diagnosing probable DAT (case 1a/1b: DAT: 11.0% in 1993 vs 26.2% in 2001; VD: 2.1% in 1993 vs 17.2% in 2001). As a possible contributor to a dementia syndrome, concomitant medication was considered only exceptionally (case 2a/2b: 4.4% in 1993 vs 2.5% in 2001). Physicians above 50 years of age showed a significantly lower early diagnostic awareness. At follow‐up, the presumed interest in geriatric (psychiatric) topics dramatically faded from 66.9% to 35.2%.

Conclusions

Our results demonstrate a persistent need of training efforts aiming at the early recognition of dementia, especially of DAT, in primary care. Copyright © 2006 John Wiley & Sons, Ltd.
Suicidal ideation among elderly homecare patients
Authors: Raue Patrick J. , Meyers Barnett S. , Rowe Jennifer L. , Heo Moonseong , Bruce Martha L.
Published: September 2006

Objectives

To identify the prevalence, correlates, and one‐year naturalistic course of suicidal ideation in a representative sample of elderly adults newly admitted to visiting nurse homecare.

Method

Five hundred and thirty‐nine participants (aged ≥65), newly initiating homecare for skilled nursing services, were interviewed with the Structured Clinical Interview for DSM‐IV (SCID‐IV) and measures of depression severity, medical comorbidity, functional status, and social support. Participants were classified as having no suicidal ideation in the past month, passive ideation, active ideation, or active ideation with poor impulse control or suicide plan.

Results

Fifty‐seven participants (10.6%) reported passive and six (1.2%) reported active suicidal ideation. Higher depression severity, greater medical comorbidity, and lower subjective social support were independently associated with the presence of any level of suicidal ideation. At one year, suicidal ideation persisted for 36.7% of those with ideation at baseline, and the incidence of suicide ideation was 5.4%

Conclusions

The high prevalence, persistence, and incidence of suicidal ideation in medically ill home healthcare patients underscore the relevance of this population for suicide prevention efforts. The clinical and psychosocial factors associated with suicidal ideation in this underserved, high‐risk population are potentially modifiable, and thus useful targets for suicide prevention interventions. Copyright © 2006 John Wiley & Sons, Ltd.
Schizotypy, marijuana, and differential item functioning
Authors: Earleywine Mitch
Published: September 2006

At least five studies report elevated schizotypy scores in cannabis users. The current research confirms higher schizotypy scores in regular cannabis users. Nevertheless, further analyses reveal that select items on the brief version of the Schizotypal Personality Questionnaire do not function comparably in current and former users. Multiple statistical approaches confirmed this problem, including the Mantel‐Haenszel statistic, Rasch difficulty estimates, a logistic regression approach, the Breslow‐Day (BD) statistic, and a combined decision rule using Mantel‐Haenszel and BD together. Cannabis users appear to misinterpret at least one item, “I sometimes use words in unusual ways” making them more likely to endorse it even if they are no more schizotypal than the former users. Users might consider cannabis‐related slang as an unusual use of words. Removing problematic items does not decrease the internal consistency of the measure, but eliminates the significant difference between current and former users. These results suggest that links between cannabis use and schizotypy require cautious interpretation and may arise from measurement problems. Copyright © 2006 John Wiley & Sons, Ltd.
Conceptual fuzzy neural network model for water quality simulation
Authors: Chaves Paulo , Kojiri Toshiharu
Published: September 2006

Artificial neural networks (ANNs) have been applied successfully in various fields. However, ANN models depend on large sets of historical data, and are of limited use when only vague and uncertain information is available, which leads to difficulties in defining the model architecture and a low reliability of results. A conceptual fuzzy neural network (CFNN) is proposed and applied in a water quality model to simulate the Barra Bonita reservoir system, located in the southeast region of Brazil. The CFNN model consists of a rationally‐defined architecture based on accumulated expert knowledge about variables and processes included in the model. A genetic algorithm is used as the training method for finding the parameters of fuzzy inference and the connection weights. The proposed model may handle the uncertainties related to the system itself, model parameterization, complexity of concepts involved and scarcity and inaccuracy of data. The CFNN showed greater robustness and reliability when dealing with systems for which data are considered to be vague, uncertain or incomplete. The CFNN model structure is easier to understand and to define than other ANN‐based models. Moreover, it can help to understand the basic behaviour of the system as a whole, being a successful example of cooperation between human and machine. Copyright © 2006 John Wiley & Sons, Ltd.
Comment on ‘M. M. Reddy, P. Schuster, C. Kendall and M. B. Reddy, characterization of surface and ground water δ18O seasonal variation and its use for estimating groundwater residence times. Hydrological Processes 20 (2006) this issue’
Authors: Criss R. E. , Winston W. E.
Published: September 2006

Reddy et al. (2006, Hydrological Processes 20: 1753–1772) disregard germane published data and successful isotopic models, selectively depict data from their data sets, misplot many of their data, and use poorly correlated sinusoidal fits to their data to derive erroneous hydrologic time constants for features in the Shingobee River Headwaters Area. A damped running average model is more realistic. Copyright © 2006 John Wiley & Sons, Ltd.
Semiempirical GGA‐type density functional constructed with a long‐range dispersion correction
Authors: Grimme Stefan
Published: September 2006

A new density functional (DF) of the generalized gradient approximation (GGA) type for general chemistry applications termed B97‐D is proposed. It is based on Becke's power‐series ansatz from 1997 and is explicitly parameterized by including damped atom‐pairwise dispersion corrections of the form C6 · R−6. A general computational scheme for the parameters used in this correction has been established and parameters for elements up to xenon and a scaling factor for the dispersion part for several common density functionals (BLYP, PBE, TPSS, B3LYP) are reported. The new functional is tested in comparison with other GGAs and the B3LYP hybrid functional on standard thermochemical benchmark sets, for 40 noncovalently bound complexes, including large stacked aromatic molecules and group II element clusters, and for the computation of molecular geometries. Further cross‐validation tests were performed for organometallic reactions and other difficult problems for standard functionals. In summary, it is found that B97‐D belongs to one of the most accurate general purpose GGAs, reaching, for example for the G97/2 set of heat of formations, a mean absolute deviation of only 3.8 kcal mol−1. The performance for noncovalently bound systems including many pure van der Waals complexes is exceptionally good, reaching on the average CCSD(T) accuracy. The basic strategy in the development to restrict the density functional description to shorter electron correlation lengths scales and to describe situations with medium to large interatomic distances by damped C6 · R−6 terms seems to be very successful, as demonstrated for some notoriously difficult reactions. As an example, for the isomerization of larger branched to linear alkanes, B97‐D is the only DF available that yields the right sign for the energy difference. From a practical point of view, the new functional seems to be quite robust and it is thus suggested as an efficient and accurate quantum chemical method for large systems where dispersion forces are of general importance. © 2006 Wiley Periodicals, Inc. J Comput Chem 2006
Similarity measures based on Gaussian‐type promolecular electron density models: Alignment of small rigid molecules
Authors: Leherte Laurence
Published: September 2006

Various molecular similarity measures (overlap, Coulomb, kinetic, electrostatic energy) and similarity indices (Carbó, Hodgkin–Richards, Kulczynski, Shape Tanimoto) are applied to the superposition of 3D promolecular electron density (PED) distributions. The original aspect of the paper lies in the consideration of smoothed PEDs, which allow to decrease the number of local solutions to a superposition problem, together with the use of the less common kinetic and electrostatic energy similarity measures. Results are obtained for a family of five rigid endothiapepsin ligands that were already considered in previous applications, based on graph representations of their PED. In the present work, it is observed that the use of smoothed PED and the kinetic similarity measure, together with the Kulczynski or Shape Tanimoto index, performed the best to align molecules of different sizes. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Tissue‐engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF‐β1 in platelet‐rich plasma
Authors: Chen Wei‐Hong , Lo Wen‐Cheng , Lee Jie‐Jen , Su Ching‐Hua , Lin Che‐Tong , Liu Hen‐Yu , Lin Tsou‐Wen , Lin Wei‐Chao , Huang Te‐Yang , Deng Win‐Ping
Published: September 2006

Human intervertebral disc (IVD) degeneration often initiated from the human nucleus pulposus (hNP) with aging leading to IVD destruction and extracellular matrix (ECM) depletion. Previously, we have successfully employed transforming growth factor‐β1 (TGF‐β1) to promote chondrogenesis of mesenchymal progenitor cells (MPCs) and immortalized human mesenchymal stem cells. In this study, we examine the role of TGF‐β1 in platelet‐rich plasma (PRP) on disc regeneration, including proliferation, redifferentiation, and the reconstitution of tissue‐engineered NP. hNP cells were isolated from volunteers with different ages and cultured in the presence of PRP. We found that the most effective concentration for hNP proliferation was 1 ng/ml TGF‐β1 in PRP, which was further applied in the following experiments. hNP cell proliferation in all age groups were increased time‐dependently by PRP and cell morphologies showed aggregation. The mRNA of Sox9, type II collagen, and aggrecan were all significantly upregulated by PRP through RT‐PCR. Glycosaminoglycan (GAG) accumulation reached the highest value at day 7 and continued to day 9 culture. PRP promoted NP regeneration via the Smad pathway was also determined and highly activated p‐Smad2/3 at 30 min and continuously sustained to 120 min. Immunostaining of type II collagen indicates that PRP participates in chondrogenesis of tissue‐engineered NP with collagen scaffolds. We concluded that growth factors in PRP can effectively react as a growth factor cocktail to induce hNP proliferation and differentiation, and also promote tissue‐engineered NP formation. These findings are the first to demonstrate that PRP might be a therapeutic candidate for prevention of disc degeneration. J. Cell. Physiol. 209: 744–754, 2006. © 2006 Wiley‐Liss, Inc.
Gene therapy for BCR‐ABL+ human CML with dual phosphorylation resistant p27Kip1 and stable RNA interference using an EBV vector
Authors: Sengupta Amitava , Banerjee Debasish , Chandra Sarmila , Banerjee Subrata
Published: September 2006

Background

BCR‐ABL‐mediated chronic myelogenous leukemia (CML) CD34+ cell proliferation mostly depends on the nucleo‐cytoplasmic ratio of the cyclin‐dependent kinase inhibitor p27. The ubiquitin‐ligase SCFSkp2 promotes degradation of phosphorylated p27 at T187 in the nucleus, resulting in G1/S progression of the cells. On the other hand, phosphatidylinositol‐3‐kinase (PI3K)‐directed T157 nuclear localization signal (NLS) phosphorylation results in cytoplasmic sequestration of p27, leading to abnormal integrin‐mediated proliferation of CD34+ CML cells.

Methods

We demonstrate the generation of an engineered Epstein‐Barr virus (EBV) vector with a BAC backbone that has the unique capacity to carry doubly modified (DM) p27 (i.e. T187A, T157A p27) along with the BCR‐ABL siRNA expression construct. The HSV‐tk suicide gene has also been incorporated in the same vector, which promotes apoptosis in a BCR‐ABL‐independent pathway.

Results

Expression of DM p27 markedly inhibits proliferation of BCR‐ABL+ primary human CML cells. Moreover, DM p27 strongly inhibits the growth of imatinib‐resistant CML cells, compared to the T157A p27 (SM p27). The CML growth inhibition is found to be the result of significant G1/S arrest with concomitant increase in hypophosphorylated retinoblastoma (Rb). Moreover, the EBV vector mediated stable RNA interference induces apoptosis in K562 cells and reduces myeloid colony forming units.

Conclusions

We therefore propose a multi‐gene delivery strategy for BCR‐ABL+ CML cells by targeting not only the fusion transcript, but also the downstream signaling, to overcome drug resistance in the acute phase of CML. Copyright © 2006 John Wiley & Sons, Ltd.
The size of minimum 3‐trees
Authors: Arocha Jorge L. , Tey Joaquín
Published: September 2006

A 3‐uniform hypergraph (3‐graph) is said to be tight, if for any 3‐partition of its vertex set there is a transversal triple. We give the final steps in the proof of the conjecture that the minimum number of triples in a tight 3‐graph on n vertices is exactly $\left\lceil n(n-2)/3 \right\rceil$. © 2006 Wiley Periodicals, Inc. J Graph Theory 54: 103–114, 2007
Synthesis and evaluation of 90Y‐DOTA‐Colchicine conjugate in murine fibrosarcoma model
Authors: Satpati Drishty , Korde Aruna , Pandey Usha , Dhami Prem , Banerjee Sharmila , Venkatesh Meera
Published: September 2006

Colchicine is a cytotoxic bioactive alkaloid that exhibits its action by microtubular binding. With an aim to develop a tumor targeted radio‐therapeutic agent, colchicine has been functionalized to trimethylcolchicinic acid and conjugated to the isothiocyanato derivative of DOTA (1,4,7,10‐tetraaza cyclododecane tetracetic acid). DOTA coupled colchicine was radiolabeled with 90Y, one of the most commonly used therapeutic radioisotope. Complexation of 200 µg of the conjugate with 90Y was carried out at pH 4.5 with an incubation time of 45 min at 70°C. Complexation yield of 90Y‐DOTA‐NCS‐colchicine was confirmed to be >98% using C‐18 reverse phase HPLC system. 90Y‐colchicine complex could be differentiated from 90Y‐p‐NCS‐benzyl‐DOTA on the basis of difference in their retention times 8 and 4 min, respectively in a standardized HPLC system. Biodistribution studies in Swiss mice fibrosarcoma tumor model showed an uptake of ∼0.8% ID/g tumor at 3 h.p.i. that was retained till 24 h.p.i. 90Y‐DOTA‐NCS‐colchicine complex showed excellent pharmacokinetics with major portion of the radioactivity being excreted out within 3 h.p.i. and no accumulation of radioactivity in vital organs. Copyright © 2006 John Wiley & Sons, Ltd.
Exacerbated loss of cell survival, neuropeptide Y‐immunoreactive (IR) cells, and serotonin‐IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line “depressed” rat: Implications for the pathophysiology of depression?
Authors: Husum H. , Aznar S. , Høyer‐Hansen S. , Larsen M. Hald , Mikkelsen J.D. , Møller A. , Mathé A.A. , Wörtwein G.
Published: September 2006

Impairment of hippocampal neurogenesis has been proposed to provide a cellular basis for the development of major depression. Studies have shown that serotonin (5‐HT) and neuropeptide Y (NPY) may be involved in stimulating cell proliferation in the dentate gyrus. The Flinders‐sensitive line (FSL) rat represents a genetic model of depression with characterized 5‐HT and NPY abnormalities in the hippocampus. Consequently, it could be hypothesized that hippocampal neurogenesis in the FSL rat would be impaired. The present study examined the relationship among 1) number of BrdU‐immunoreactive (IR) cells, 2) NPY‐IR cells in the dentate gyrus, and 3) length of 5‐HT‐IR fibers in the dorsal hippocampus, as well as volume and number of 5‐HT‐IR cells in the dorsal raphé nucleus, in adult and aged FSL rats and control Flinders‐resistant line (FRL) rats. Surprisingly, adult FSL rats had significantly more BrdU‐IR and NPY‐IR cells compared with adult FRL rats. However, aging caused an exacerbated loss of these cell types in the FSL strain compared with FRL. The aged FSL rats also had shortened 5‐HT‐IR fibers in the dorsal hippocampus, indicative of an impaired 5‐HT innervation of this area, compared with FRL. These results suggest that, for “depressed” FSL rats, compared with FRL rats, aging is associated with an excacerbated loss of newly formed cells in addition to NPY‐IR cells and 5‐HT‐IR dendrites in the hippocampus. These observations may be of relevance to the depression‐like behavior of the FSL rat and, by inference, to the pathophysiology of depression. © 2006 Wiley‐Liss, Inc.
Evidence for the presence of the type 2 corticotropin releasing factor receptor in the rodent cerebellum
Authors: Bishop Georgia A. , Tian Jin Bin , Stanke Jennifer J. , Fischer Andy J. , King James S.
Published: September 2006

Corticotropin releasing factor (CRF), localized in afferent inputs to the cerebellum, binds to two receptors defined as the Type 1 (CRF‐R1) and the Type 2 (CRF‐R2α). CRF‐R1 has been localized to the cerebellum, as has a truncated isoform of CRF‐R2α. Evidence for the presence of the full length isoform of CRF‐R2α in the cerebellum is conflicting. We used RT‐PCR, immunohistochemical, and physiologic techniques to resolve this conflict. RT‐PCR data show low levels of CRF‐R2α in the vermis and hemisphere of the cerebellum. These observations were confirmed by the Gene Expression Nervous System Atlas (GENSAT) database. A CRF‐R2α antibody was used to determine the cellular distribution of the receptor in the cerebellum. The vast majority of the receptors are localized to Bergmann glial cells located throughout the cerebellum, as well as astrocytes in the granule cell layer. Neuronal labeling is present in sub‐populations of Purkinje cells, Golgi cells, basket cells, and cerebellar nuclear neurons. Physiologic data show that urocortin II, which binds selectively to CRF‐R2α, increases the firing rate of both Purkinje cells and nuclear neurons; this response can be blocked by the CRF‐R2α‐specific antagonist, antisauvagine‐30. The present results confirm that CRF‐R2α is present in the cerebellum and functions in circuits that modulate the firing rate of Purkinje cells and cerebellar nuclear neurons. A comparative analysis showed that the patterns of distribution of CRF‐R1, CRF‐R2α and CRF‐R2α‐tr are distinct. These data indicate that the CRF family of peptides modulates cerebellar output by binding to multiple CRF receptors. © 2006 Wiley‐Liss, Inc.
Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis
Authors: Hindinger Claudia , Hinton David R. , Kirwin Stefanie J. , Atkinson Roscoe D. , Burnett Margaret E. , Bergmann Cornelia C. , Stohlman Stephen A.
Published: September 2006

Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T‐cell proliferation and cytokine release in a dose‐dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination. In contrast to in vitro analysis, no reductions in peripheral neuroantigen specific T‐cell responses were detected in comparing ligand and vehicle treated mice. These data suggest that LXR agonists play an important protective role in the regulation of T‐cell‐mediated inflammatory disease of the central nervous system. © 2006 Wiley‐Liss, Inc.
The immunosuppressant rapamycin exacerbates neurotoxicity of Aβ peptide
Authors: Lafay‐Chebassier Claire , Pérault‐Pochat Marie Christine , Page Guylène , Bilan Agnès Rioux , Damjanac Milena , Pain Stéphanie , Houeto Jean‐Luc , Gil Roger , Hugon Jacques
Published: September 2006

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system characterized by two major lesions: extracellular senile plaques and intraneuronal neurofibrillary tangles. β‐Amyloid (Aβ) is known to play a major role in the pathogenesis of AD. Protein synthesis and especially translation initiation are modulated by different factors, including the PKR/eIF2 and the mTOR/p70S6K pathways. mRNA translation is altered in the brain of AD patients. Very little is known about the translation control mediated by mTOR in AD, although mTOR is a central regulator of translation initiation and also ribosome biogenesis and cell growth and proliferation. In this study, by using Western blotting, we show that mTOR pathway is down‐regulated by Aβ treatment in human neuroblastoma cells, and the underlying mechanism explaining a transient activation of p70S6K is linked to cross‐talk between mTOR and ERK1/2 at this kinase level. This phenomenon is associated with caspase‐3 activation, and inhibition of mTOR by the inhibitor rapamycin enhances Aβ‐induced cell death. Moreover, in our cell model, insulin‐like growth factor‐1 is able to increase markedly the p70S6K phosphorylation controlled by mTOR and reduces the caspase‐3 activity, but its protective effect on Aβ cell death is mediated via an mTOR‐independent pathway. These results demonstrate that mTOR plays an important role as a cellular survival pathway in Aβ toxicity and could represent a possible target for modulating Aβ toxicity. © 2006 Wiley‐Liss, Inc.
Functional modulation of parkin through physical interaction with SUMO‐1
Authors: Um Ji Won , Chung Kwang Chul
Published: September 2006

Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the extensive and progressive loss of dopaminergic neurons in the CNS substantia nigra pars compacta region. Mutations in the parkin gene, which encodes for E3 ubiquitin ligase, have been implicated in autosomal recessive juvenile parkinsonism, an early‐onset and common familial form of PD. Although several parkin substrates have already been identified, the molecular mechanism underlying the regulation of enzymatic activity of parkin has yet to be clarified. In a previous study, we demonstrated that RanBP2 becomes a new target for parkin E3 ubiquitin ligase and is processed via parkin‐mediated ubiquitination and subsequent proteasomal degradation. RanBP2, which is localized in the cytoplasmic filament of the nuclear pore complex, belongs to the small ubiquitin‐related modifier (SUMO) E3 ligase family. Here we show that parkin appears to bind selectively to the SUMO‐1 in vivo and in vitro. Moreover, the physical association of SUMO‐1 with parkin results in an increase in the nuclear transport of parkin as well as its self‐ubiquitination. Our findings suggest that the E3 ubiquitin ligase activity of parkin and its intracellular localization may be modulated through the SUMO‐1 association. © 2006 Wiley‐Liss, Inc.
Suprachiasmatic astrocytes as an interface for immune‐circadian signalling
Authors: Leone María Juliana , Marpegan Luciano , Bekinschtein Tristán A. , Costas Mónica A. , Golombek Diego A.
Published: September 2006

The hypothalamic suprachiasmatic nuclei (SCN), the site of a mammalian circadian clock, exhibit a dense immunoreactivity for glial fibrillary acidic protein (GFAP), a specific marker for astrocytes. Although there is evidence of a circadian variation in GFAP‐IR in the hamster SCN and of the participation of glial cells in input and output mechanisms of the clock, the role of these cells within the circadian system is not clearly understood. The fact that astroglia can express and respond to cytokines suggests that they could work as mediators of immune signals to the circadian system. In the present study, we have found a daily variation of GFAP‐IR in the mouse SCN, peaking during the light phase. In addition, we have identified GFAP and nuclear factor‐κB (NF‐κB) in glial cells within the SCN and in primary cultures of the mouse SCN. Moreover, SCN glia cultures were transfected with an NF‐κB/luc construct whose transcriptional activity was increased with lipopolysaccharide 2 μg/ml, tumor necrosis factor‐α 20 ng/ml, or interleukin‐1α 100 ng/ml, after 12 hr of stimulation. These results suggest that the glial cells of the SCN can mediate input signals to the mouse circadian system coming from the immune system via NF‐κB signaling. © 2006 Wiley‐Liss, Inc.
Ascorbic acid, aroma compounds and browning of orange juices related to PET packaging materials and pH
Authors: Berlinet Cécilia , Brat Pierre , Brillouet Jean‐Marc , Ducruet Violette
Published: September 2006

The ascorbic acid content of orange juice made from concentrate was measured after 9 months of storage at 20 °C in glass, standard monolayer polyethylene terephthalate (PET1), multilayer PET (PET2) and plasma‐treated PET (PET3) containers. Glass enabled the best preservation of ascorbic acid and, in plastic packaging materials, ascorbic acid losses were correlated with their oxygen permeability. PET2 and PET3, which exhibit oxygen permeability 10 times less than that of PET1, enabled a gain of 100 mg L−1 after 9 months of storage. Freshly hand‐squeezed orange juice samples were adjusted to various pH values using sodium hydroxide; a rise in the pH from 3.2 to 4.0 significantly reduced the amounts of off‐flavours (i.e., furfural and α‐terpineol) appearing during storage, by 79% and 65%, respectively. Moreover, an increase in the pH from 3.2 to 4.0 enabled the protection of ascorbic acid levels without detrimentally increasing non‐enzymatic browning. Copyright © 2006 Society of Chemical Industry
Influence of branch bending on sugar, organic acid and phenolic content in fruits of ‘Williams’ pears (Pyrus communis L.)
Authors: Colaric Mateja , Stampar Franci , Solar Anita , Hudina Metka
Published: September 2006

Selected sugars, organic acids and phenolic compounds were analysed in mature fruits of ‘Williams’ pears using high‐performance liquid chromatography. Fruits were harvested from the branches of trees tested in three treatments: branches were bent in summer 2003 (1 September), in spring 2004 (15 May) and control (branches were not bent). Pears contained up to 73.54 g kg−1 fresh weight (FW) of fructose, 9.42 g kg−1 FW of glucose, 7.94 g kg−1 FW of sucrose and 24.59 g kg−1 FW of sorbitol. Major organic acids were (in order of descending quantity) citric, malic, shikimic and fumaric acid (up to 3.05 g kg−1 FW, 2.24 g kg−1 FW, 71.79 mg kg−1 FW and 0.49 mg kg−1 FW, respectively). Chlorogenic acid (280.86–357.34 mg kg−1 FW) was the predominant phenolic acid, followed in concentration (mg kg−1 FW) by syringic acid (95.46–131.32), epicatechin (46.55–83.09), catechin (25.67–44.81), vanillic acid (1.87–3.48), sinapic acid (0.83–1.72) and caffeic acid (0.72–1.04). Significant differences in content of fructose, sorbitol, total sugars, catechin, epicatechin, sinapic acid, syringic acid, and a sum of determined phenolic compounds were observed among the treatments. Fruits from summer bending branches had the lowest content of individual sugars, citric acid and phenolic compounds and the highest content of malic, shikimic and fumaric acid. The highest content of fructose, sorbitol, sucrose, total sugars, caffeic acid, catechin, epicatechin and syringic acid were determined in the fruits from the spring treatment. In the control treatment the highest content of glucose, citric acid, chlorogenic acid, sinapic acid, vanillic acid, as well a sum of determined phenolics, were observed. The lowest content of fumaric acid was in the spring treatment and of malic and shikimic acid in the control. Copyright © 2006 Society of Chemical Industry
Rapid phase‐compositional assessment of lipid‐based food products by time domain NMR
Authors: Trezza E. , Haiduc A. M. , Goudappel G. J. W. , van Duynhoven J. P. M.
Published: September 2006

In food science and technology, assessment of phase‐compositional behaviour of lipids is critical for understanding many product properties and for effective process control. Time Domain NMR is a rapid and easy‐to‐handle technique, and is already well appreciated as a tool for phase‐compositional assessment in foods. The phase‐compositional detail that can be obtained with the established methodology is limited, however. In this work, we set out to obtain more phase‐compositional details of lipids as currently feasible with the already established ‘classical’ NMR methods. We deployed a combined FID‐CPMG experiment, and analyzed the Transversal Relaxation Decays by Deconvolution (TRDD) with semi‐empirical mathematical functions for solid, semi‐solid and liquid components. Within the solid component, different lipid crystal polymorphs can be discerned in a quantitative manner, i.e. α, β and β′. The TRDD method was validated against established NMR SFC methods, in terms of accuracy (‘trueness’) and precision. The solid fat content (SFC) of a large collection of fat blends was measured by the commonly employed NMR Direct and Indirect SFC methods and a good correlation with the results of the TRDD was observed, thereby demonstrating accuracy. Furthermore, TRDD was found to be equally precise as the established NMR SFC methods. Copyright © 2006 John Wiley & Sons, Ltd.
Structural determination of diterpenes from Daphne genkwa by NMR spectroscopy
Authors: Akhtar Kalsoom , Bahadar Khan Sher , Ali Irshad
Published: September 2006

Five daphnane type diterpenes have been isolated from the chloroform soluble fraction of Daphne genkwa. The structure of the new compound (1) was assigned as 5β‐hydroxyresiniferonol‐6α,7α‐epoxy‐12β‐acetoxy‐9,13,14‐ortho‐2E‐decenoate by extensive NMR studies. Copyright © 2006 John Wiley & Sons, Ltd.
Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in uteri of ovariectomized mice after treatment with ovarian steroid hormones
Authors: Fritzsche Britta , Vermot Julien , Neumann Ulrike , Schmidt Anja , Schweigert Florian J. , Dollé Pascal , Rühl Ralph
Published: September 2006

The retinoic acid (RA) synthesizing enzymes, retinaldehyde dehydrogenases (RALDH), are expressed in specific spatial and temporal patterns in uterine tissues during estrous cycle and early pregnancy in mice. Expression of RALDH1 and 2 has been shown to be induced by estrogen treatment within the uterus. In this study, we determined the influence of progesterone and 17‐ß‐estradiol on the uterine expression of the RA‐metabolizing enzyme CYP26A1 after specific time intervals (1, 4, 24, and 48 hr after treatment of ovariectomized mice). In a following experiment, we investigated the influence of gestagen (promegestone 0.3 mg/kg body weight), estrogen (estradiol 3 µg/kg), their combination, as well as the antagonizing anti‐progesterone hormone (RU 486 10 mg/kg) on the uterine expression of CYP26A1. Expression of CYP26A1 was localized using in situ hybridization and quantified using RT‐PCR. CYP26A1 mRNA expression was strongly—although transiently—induced in uterine endometrial epithelial and glandular cells after administration of gestagen or the combination of gestagen + estrogen, but not by estrogen alone. These observations were confirmed by semi‐quantitative RT‐PCR experiments on whole uteri. Thus, we show that the expression of CYP26A1 in endometrial epithelial cells is regulated by progesterone and not significantly influenced by co‐administration of estrogen. These data indicate an additional level of hormonal control of endogenous RA levels in the mouse uterus, where its synthesis would rely on estrogen‐dependent expression of RALDH enzymes, whereas its active metabolism would be triggered by progesterone‐induced CYP26A1 expression. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Identification of a heat‐shock protein Hsp40, DjB1, as an acrosome‐ and a tail‐associated component in rodent spermatozoa
Authors: Doiguchi Masamichi , Kaneko Takane , Urasoko Aiko , Nishitani Hideo , Iida Hiroshi
Published: September 2006

Iba1 is a 17‐kDa EF‐hand protein highly expressed in the cytoplasm of elongating spermatids in testis. Using Iba1 as a bait, we performed yeast Two‐hybrid screening and isolated a heat‐shock protein Hsp40, DjB1, from cDNA library of mouse testis. To characterize DjB1 that is encoded by Dnajb1 gene, we carried out immunoblot analyses, in situ hybridization, and immunohistochemistry. Immunoblot analyses showed that DjB1was constitutively expressed in mouse testis and that its expression level was not changed by heat shock. Dnajb1 mRNA was exclusively expressed in spermatocytes and round spermatids in mouse testis, and Dnajb1 protein DjB1 was predominantly expressed in the cytoplasm of spermatocytes, round spermatids, and elongating spermatids. In mature mouse spermatozoa, DjB1 was localized in the middle and the end pieces of flagella as well as in association with the head (acrosomal region). Association of DjB1 with the acrosomal region in sperm head was also observed in rat spermatozoa. These data suggested that DjB1, which was constitutively expressed in postmeiotic spermatogenic cells in testis, was integrated into spermatozoa as at least two components, that is, sperm head and tail of rodent spermatozoa. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.