bluuebunny/crossref_metadata_2025 huggingface dataset:
A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of ‘vascular depression’
Authors: Taragano Fernando E. , Allegri Ricardo , Vicario Augusto , Bagnatti Pablo , Lyketsos Constantine G.
Published: January 2005

Background

‘Vascular depression’ may be caused by cerebrovascular disease. Calcium channel blockers, which are putative treatments for cerebrovascular disease, might be expected to improve depression reduction and to prevent recurrence of depression in this patient population. This clinical trial was designed to test these hypotheses.

Design

This was a controlled, double blind, randomized clinical trial in which 84 patients with vascular depression (Alexopoulos criteria) were treated with antidepressants at standard doses. Patients were also randomized to nimodipine (n = 40) or an inactive comparator, vitamin C (n = 44). Treatment outcomes were assessed using the Hamilton depression rating scale (HDRS) regularly up to 300 days after treatment initiation.

Results

As expected, depression reduction was successful in most patients. In addition, those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA (F(1,81) = 8.64, p = 0.004). As well a greater proportion of nimodipine‐treated participants (45 versus 25%) exhibited a full remission (HDRS ≤10) (χ2(df, 1) = 3.71, p = 0.054). Among those experiencing a substantial response in the first 60 days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a recurrence of major depression when compared to those on antidepressant alone (32%) (χ2(df, 1) = 3.59, p = 0.058).

Conclusions

In treating vascular depression, augmentation of antidepressant therapy with a calcium‐channel blocker leads to greater depression reduction and lower rates of recurrence. These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients. Copyright © 2001 John Wiley & Sons, Ltd.
The effectiveness of very short scales for depression screening in elderly medical patients†
Authors: Pomeroy Ian M. , Clark Christopher R. , Philp Ian
Published: January 2005

Objective

To compare very short scales for screening for depression with longer, widely used scales.

Methods

Eighty‐seven patients over the age of 60 who were admitted to rehabilitation wards or were attending a day rehabilitation facility at a British teaching hospital were screened for depression using the 1‐item mental health inventory, and the 4‐item, 15‐item and 30‐item geriatric depression scales. The sensitivity, specificity, and areas under receiver operating characteristic curves were compared, with the diagnostic criteria for research of ICD‐10 providing the criterion diagnosis of depressive episode.

Results

All the scales had comparable sensitivity (82.4–100%), specificity (60.0–71.4%), and positive predictive values (33.3–42.9%). Comparison of receiver operating characteristic curves for each scale showed no statistically significant difference between them (range 0.80–0.88).

Conclusions

The very short scales performed just as well as the widely used longer screening scales in this population. They are worthy of further examination in elderly populations at risk of depression, and may be particularly suitable for older adults due to their brevity and ease of use. Copyright © 2001 John Wiley & Sons, Ltd.
Reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale
Authors: Marin Deborah B. , Flynn Sean , Mare Marlene , Lantz Melinda , Hsu Ming‐Ann , Laurans Max , Paredes Maria , Shreve Tricia , Zaklad Gabrielle R. , Mohs Richard C.
Published: January 2005

Objective

This study investigated the reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale (CDR‐CC).

Method

Sixty‐two residents in a chronic care facility participated in an inter‐rater and 1 month test–retest reliability study. The instrument was validated against the Mini‐Mental State Examination (MMSE).

Results

Inter‐rater and 1 month test–retest reliability for the global CDR‐CC score were excellent (intraclass correlation coefficients 0.99 and 0.92, respectively). The CDR‐CC domain and global scores were negatively correlated with the MMSE.

Conclusions

The CDR‐CC is a global assessment tool that reliably and validly measures cognitive and functional impairment in a chronic care setting. Copyright © 2001 John Wiley & Sons, Ltd.
Memory rehabilitation in Alzheimer's disease: a review of progress
Authors: De Vreese Luc P. , Neri Mirco , Fioravanti Mario , Belloi Luciano , Zanetti Orazio
Published: January 2005

Background

Memory rehabilitation is a sadly misrepresented area of applied research in Alzheimer's disease.

Objectives

To gather and evaluate recent evidence for the clinical effectiveness or ecologically validity of memory rehabilitation for mild to moderate Alzheimer's patients.

Methods

Computerised searches and some handsearching were conducted spanning the last five years, from 1995 to 2000, inclusively. Criteria for inclusion in this overview involved the use of a precise memory rehabilitation technique within an experimental study design applied to Alzheimer's patients with pre‐ and post‐treatment evaluation.

Findings

Three potential levels of memory rehabilitation procedures with proven clinical or pragmatic efficacy were identified. The first level bears on the facilitation of residual explicit memory with structured support both at encoding and at subsequent recall; the second level of memory rehabilitation exploits the relatively intact implicit memory system (priming and procedural memory); the last deals with finding ways of coping with the patient's limited explicit memory capacities through the use of external memory aids. A proposal of suggestions for good practice and future research in memory rehabilitation is also offered with the hope to spur further development in this rapidly expanding area of applied research.

Conclusion

The available evidence shows that alternative and innovative ways of memory rehabilitation for Alzheimer's patients can indeed be clinically effective or pragmatically useful with a great potential for use within the new culture of a more graded and proactive type of Alzheimer's disease care. Copyright © 2001 John Wiley & Sons, Ltd.
Elderly Japanese emigrants to Brazil before World War II: II. prevalence of senile dementia
Authors: Meguro Kenichi , Meguro Mitsue , Caramelli Paulo , Ishizaki Junichi , Ambo Hideo , Chubaci Rosa Y. S. , Hamada Gerson S. , Nitrini Ricardo , Yamadori Atsushi
Published: January 2005

Background

We previously showed the prevalence of dementia in the town of Tajiri (Miyagi Prefecture, Japan), and found it to be 8.0%.The first population‐based study on dementia in Brazil (Catanduva) disclosed the prevalence as being 7.1%. To evaluate the effects of environment on development of dementia, elderly Japanese immigrants living in Brazil were examined. Brazil is the country with the largest number of Japanese immigrants.

Methods

All immigrants aged 65 years and over from Miyagi Prefecture, living in the four cities of the São Paulo Metropolitan area were targeted (n = 192). We were able to examine 166 subjects (86.5%). The diagnosis of dementia was based on the DSM‐IV with the severity assessed by the CDR (clinical dementia rating) scales. The cognitive ability screening instrument (CASI) was used for neuropsychological assessment.

Results

Thirteen subjects were diagnosed with dementia, CDR 1–3, the prevalence being 7.8%. Older subjects suffered more from dementia, and, paradoxically, the more highly educated subjects also suffered more. All the CASI items, except for long‐term memory and visual construction, significantly deteriorated in the CDR 0.5 group compared with the CDR 0 group.

Comments

The prevalence of dementia was not thought to be affected by environmental factors. A paradoxically higher rate of dementia in the more educated subjects was probably due to the historical problems of the immigrants. Intact CASI item long‐term memory in the CDR 0.5 group indicated that suspected dementia patients could maintain this function. This is the first epidemiological study on dementia in elderly Japanese immigrants in Brazil. Copyright © 2001 John Wiley & Sons, Ltd.
Depressive symptoms and associated factors in a cognitively normal elderly population: the Tajiri Project
Authors: Ambo Hideo , Meguro Kenichi , Ishizaki Junichi , Shimada Masumi , Yamaguchi Satoshi , Sekita Yasuyoshi , Yamadori Atsushi
Published: January 2005

Background and objective

Since depression is one of the main problems of elderly subjects, it is important to examine the prevalence of this condition and to identify associated factors.

Methods

A total of 1525 cognitively normal subjects aged 65 years and over in the town of Tajiri, a typical agricultural town in Japan, were analysed. Their MMSE (mini‐mental state examination) scores were 24 or over. Depressive state was assessed by Zung's SDS (self‐rating depression scale) with a comprehensive interview to examine ADL, demographics and symptoms associated with illness, etc. The prevalence of depression was calculated. To determine the factors associated with depression, the t‐test and the Chi‐square test were used. To examine the relative strength of each factor, logistic regression analysis was performed.

Results

The ratio of the depressive subjects was 6.4%, lower than those of previous reports, probably due to the effect of excluding dementia subjects. The ratio for older females aged 80 years and over was 14.3%, which was significantly higher than that of the males. Among socio‐demographic factors, sex, age, number of children and perception of economic status, were significantly related. For health status and ADL, such factors as perception of health and medical history of heart disease and rheumatism were related. For familial and social status, factors such as daily activity and several conversation abilities were related. The logistic regression analysis indicated that perception of health and daily activity were associated.

Conclusions

In this study, we isolated some factors related to depression in a cognitively normal population. Knowledge of such factors is important for appropriate mental care of aged subjects. Copyright © 2001 John Wiley & Sons, Ltd.
Treatment‐emergent behavioural side effects with selective serotonin re‐uptake inhibitors in adults with learning disabilities
Authors: Biswas A. B. , Bhaumik S. , Branford D.
Published: January 2005

Selective serotonin re‐uptake inhibitors are widely used for the treatment of depression suffered by adults with learning disabilities. However, the presentation, time of onset and prevalence of treatment emergent symptoms, have not been extensively studied in adults with learning disabilities. The aim of this study was to determine these aspects of treatment. The study design involved retrospective analysis of case notes of all adults with learning disabilities treated with either fluoxetine or paroxetine for depression. During 31% of treatment episodes, patients suffered treatment emergent symptoms during treatment with either selective serotonin re‐uptake inhibitor (SSRI). These symptoms subsided on discontinuation of the SSRI. The common emergent symptoms in this group were elevated mood (39%), decreased sleep (35%), hyperactivity (30%), overtalkativeness (26%), agitation (24%) and aggression (37%). In 20% symptoms developed within 1 month and in 67% within 7 months of starting treatment with a SSRI. There were no significant differences noted in the frequency and nature of treatment emergent symptoms between fluoxetine and paroxetine. Few guidelines, if any, exist for initiating and continuing antidepressant treatment for therapeutic or prophylactic use in this patient population. Close monitoring of efficacy and tolerability, including treatment emergent psychiatric symptoms is warranted. Copyright © 2001 John Wiley & Sons, Ltd.
Zolpidem and triazolam interact differentially with a delay interval on a digit‐enter‐and‐recall task
Authors: Rush Craig R. , Baker Robert W.
Published: January 2005

Zolpidem (AMBIEN®), an imidazopyridine, is now the most commonly prescribed hypnotic in the United States. Zolpidem is neuropharmacologically distinct from benzodiazepine hypnotics in that it binds with low affinity to α5‐containing GABAA‐receptor subtypes. Despite its unique benzodiazepine‐receptor binding profile, the results of most of the published studies conducted with humans suggest that the absolute magnitude of impairment produced by zolpidem is comparable to that observed with benzodiazepine hypnotics like triazolam. The present study compared the acute effects of zolpidem (0, 7.5, 15 and 22.5 mg) and triazolam (0, 0.1875, 0.375 and 0.5625 mg) in 10 non‐drug‐abusing humans using a Digit‐Enter‐and‐Recall task with varying delay intervals (0, 10 and 20 s). To more fully characterize the behavioral effects of zolpidem and triazolam, several other performance tasks and subject‐rated drug‐effect questionnaires were included. Zolpidem and triazolam impaired performance on the Digit‐Enter‐and‐Recall task as a function of dose under all delay intervals. However, the dose‐related effects of the drugs interacted differentially with the delay interval such that zolpidem produced significantly less impairment than triazolam following the longest delay (i.e., 20 s). Zolpidem and triazolam produced comparable dose‐related impairment on the digit symbol substitution test (DSST), circular lights task, and picture recall/recognition task. Zolpidem and triazolam generally produced qualitatively and quantitatively similar subject‐rated drug effects, although some between‐drug differences were observed. Consistent with the pharmacokinetics of these drugs, the effects of zolpidem peaked sooner and were shorter in duration than those observed with triazolam. The results of this experiment suggest that zolpidem may have less potential than triazolam to impair recall, which may be due to differences between these compounds in terms of their benzodiazepine‐receptor binding profile. The results of the present study are also concordant with previous studies that found that drugs that act at the GABAA‐receptor complex can be differentiated based on their interaction with the delay interval on a Digit‐Enter‐and‐Recall task. Copyright © 2001 John Wiley & Sons, Ltd.
Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening
Authors: Hindmarch Ian , Patat Alain , Stanley Neil , Paty Isabelle , Rigney Una
Published: January 2005

The objective was to assess residual effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double‐blind, placebo‐controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg. A battery of objective tests exploring psychomotor and cognitive functions such as critical flicker fusion (CFF), choice reáction time (CRT), digit symbol substitution test (DSST), and memory tests (Sternberg memory scanning and a word list) were administered immediately after morning waking. Zaleplon 10 mg was devoid of residual effects whatever – the time of dosing – except a minimal but significant decrease in DSST scores when administered 1 h before awakening. Zaleplon 20 mg produced significant residual effects on performance (increase in CRT, and decrease in CFF threshold and in DSST scores) and memory (decrease in immediate and delayed free recall of words) only when administered 1 h before awakening. In contrast, zolpidem 10 mg produced significant detrimental residual effects on CRT and delayed free recall of words, when administered up to 5 h before waking, on DSST and Sternberg when administered up to 3 h before awakening and on CFF when administered 1 h before awakening. The residual effects of zolpidem 10 mg were more marked than those observed after zaleplon 20 mg. The present results demonstrate that zaleplon 10 mg has no or minimal residual effects when administered in the middle of the night as little as 1 h before waking. The lack of clinically significant residual effects with zaleplon may be explained by its unique pharmacokinetic (rapid elimination half‐life) and pharmacodynamic (selective binding for GABAA receptors with the α1 subunit, dissociation between sleep inducing properties and impairment of cognitive functions) profiles. Copyright © 2001 John Wiley & Sons, Ltd.
Mirtazapine and paroxetine: a drug‐drug interaction study in healthy subjects
Authors: Ruwe F. J. L. , Smulders R. A. , Kleijn H. J. , Hartmans H. L. A. , Sitsen J. M. A.
Published: January 2005

Paroxetine inhibits cytochrome P450 2D6, which is involved in the metabolism of mirtazapine. The possible drug‐drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three‐way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug‐drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright © 2001 John Wiley & Sons, Ltd.
Differential efficacy of risperidone versus haloperidol in psychopathological subtypes of subchronic schizophrenia
Authors: Cavallaro R. , Mistretta P. , Cocchi F. , Manzato M. , Smeraldi E.
Published: January 2005

The aim of this study was to evaluate the efficacy and tolerability of risperidone versus haloperidol in subchronic schizophrenia, using psychopathological subgroups of patients with negative or positive and mixed symptoms to analyse the possible differential efficacy of the drugs. A total of 33 patients diagnosed using DSM‐IV criteria entered the 6 week double‐blind study with either risperidone or haloperidol 5 mg/day. Twenty‐nine patients completed at least 2 weeks of treatment and entered the last observation carried‐forward analysis. Both treatments were effective in reducing total scores and positive and negative subscale scores on the Positive and Negative Scale for Schizophrenia (PANSS), with a significantly better extrapyramidal profile in the risperidone‐treated group. When analysis was repeated in each treatment group by psychopathological subtype (negative vs positive‐mixed subgroups based on the PANSS composite index), risperidone was significantly superior to haloperidol in the intention to treat analysis in the negative subgroup. Repeated measures multivariate analysis of variance showed a significantly greater improvement in the PANSS negative subscale scores of risperidone‐treated patients in the negative subgroup and a significant improvement in the PANSS positive subscale scores in both psychopathological subtypes. Haloperidol was significantly effective only in reducing positive symptoms in the positive subtype. Our results indicate that risperidone may be proposed for first‐line treatment of subchronic schizophrenia, in particular the negative subtype. Copyright © 2001 John Wiley & Sons, Ltd.
Validation of a vegetated filter strip model (VFSMOD)
Authors: Abu‐Zreig Majed , Rudra R. P. , Whiteley H. R.
Published: January 2005

Vegetated filter strips (VFS) are designed to reduce sediment load and other pollutants into water bodies. However, adaptation of VFS in the field has been limited owing to lack of data about their efficiency and performance under natural field conditions. A number of models are available that simulate sediment transport and trapping in VFS, but there is a general lack of confidence in VFS models owing to limited validation studies and model limitations that prevent correct application of these models under field conditions. The objective of this study is to test and validate a process‐based model (VFSMOD) that simulates sediment trapping in VFS. This model links three submodels: modified Green–Ampt's infiltration, Quadratic overland flow submodel based on kinematic wave approximation and University of Kentucky sediment filtration model. A total of 20 VFS, 2, 5, 10 and 15 m long and with various vegetation covers, were tested under simulated sediment and runoff conditions. The results of these field experiments were used to validate the VFS model. The model requires 25 input parameters distributed over five input files. All input parameters were either measured or calculated using experimental data. The observed sediment trapping efficiencies varied from 65% in the 2‐m long VFS to 92% in the 10‐m long filters. No increase in sediment removal efficiency was observed at higher VFS length. Application of the VFS model to experimental data was satisfactory under the condition that actual flow widths are used in the model instead of the total filter width. Predicted and observed sediment trapping efficiencies and infiltration volume fitted very well, with a coefficient of determination (R2) of 0·9 and 0·95, respectively. Regression analyses revealed that the slope and intercept of the regression lines between predicted versus observed infiltration volume and trapping efficiency were not significantly different than the line of perfect agreement with a slope of 1·0 and intercept of 0·0. Copyright © 2001 John Wiley & Sons, Ltd.
Nutrient fluxes at the river basin scale. I: the PolFlow model
Authors: Wit M. J. M. de
Published: January 2005

Human activity has resulted in increased nutrient levels in rivers and coastal seas all over Europe. Models that can describe nutrient fluxes from pollution sources to river outlets may help policy makers to select the most effective source control measures to achieve a reduction of nutrient levels in rivers and coastal seas. Part I of this paper describes the development of such a model: PolFlow. PolFlow was specially designed for operation at the river basin scale and is here applied to model 5‐year average nitrogen and phosphorus fluxes in two European river basins (Rhine and Elbe) covering the period 1970–1995. Part II reports an error analysis and model evaluation, and compares PolFlow to simpler alternative models. Copyright © 2001 John Wiley & Sons, Ltd.
Nutrient fluxes at the river basin scale. II: the balance between data availability and model complexity
Authors: de Wit M. J. M. , Pebesma E. J.
Published: January 2005

In order to model complex environmental systems, one needs to find a balance between the model complexity and the quality of the data available needed to run and validate the model. This paper describes a method to find this balance. Four models of different complexity were applied to describe the transfer of nitrogen and phosphorus from pollution sources to river outlets in two large European river basins (Rhine and Elbe). A comparison of the predictive capability of these four models tells us something about the added value of the added model complexity. We also quantified the errors in the data that were used to run and validate the models and analysed to what extent the model validation errors could be attributed to data errors, and to what extent to shortcomings of the model. We conclude that although the addition of more process description is interesting from a theoretical point of view, it does not necessarily improve the predictive capability. Although our analysis is based on an extensive pollution‐sources–river‐load database it appeared that the information content of this database was sufficient only to support models of a limited complexity. Our analysis also illustrates that for a proper justification of a model's degree of complexity one should compare the model to simplified versions of the model. Copyright © 2001 John Wiley & Sons, Ltd.
Hydrogeological aspects of groundwater drainage of the urban areas in Kuwait City
Authors: Al‐Rashed Muhammad F. , Sherif Mohsen M.
Published: January 2005

Residential areas in Kuwait City have witnessed a dramatic rise in subsurface water tables over the last three decades. This water rise phenomenon is attributed mainly to over irrigation practices of private gardens along with leakage from domestic and sewage networks. This paper presents a comprehensive study for urban drainage in two selected areas representing the two hydrogeological settings encountered in Kuwait City. In the first area, a vertical drainage scheme was applied successfully over an area of 1 km2. The system has been under continuous operation and monitoring for more than 4 years without problems, providing a permanent solution for the water rise problem in this area. The hydrogeological system has approached steady state conditions and the water levels have dropped to about 3·5 m below the ground surface. In the second area a dual drainage scheme, composing of horizontal and vertical elements, is proposed. Horizontal elements are suggested in the areas where the deep groundwater contains hazardous gases that may pose environmental problems. The proposed drainage scheme in the second area has not yet been implemented. Field tests were conducted to assess the aquifer parameters in both areas and a numerical model has been developed to predict the long‐term response of the hydrogeological system in the two areas under consideration. Copyright © 2001 John Wiley & Sons, Ltd.
The effect of mining and related activities on the sediment–trace element geochemistry of Lake Coeur d'Alene, Idaho, USA. Part III. Downstream effects: the Spokane River Basin
Authors: Grosbois Cecile A. , Horowitz Arthur J. , Smith James J. , Elrick Kent A.
Published: January 2005

During 1998/1999, surface and subsurface sediment samples were collected along the entire length of the Spokane River from its outlet at the northern end of Lake Coeur d'Alene (CDA), Idaho, to Lake Roosevelt on the Columbia River, Washington. The study was conducted to determine if the trace element enrichments observed in Lake CDA and on the floodplain and in the CDA River extend through the Spokane River Basin (SRB).

As in Lake CDA, surface sediments in the SRB are enriched in Pb, Zn, As, Cd, Sb and Hg relative to local background levels. Pb, Cd and Zn are the most elevated, with maximum enrichment occurring in the upper Spokane River in close proximity to Lake CDA. On average, enrichment decreases downstream, apparently reflecting both increased distance from the inferred source (the CDA River Basin), as well as increased dilution by locally derived but unenriched materials. Only Cd and Zn display marked enrichment throughout the SRB. Pb, Zn and Cd seem to be associated mainly with an operationally defined iron oxide phase, whereas the majority of the As and Sb seem to be matrix‐held.

Subsurface sediments also are enriched in Pb, Zn, As, Cd, Sb and Hg relative to background levels. Based on 137Cs and excess 210Pb dating, trace element enrichment began in the middle part of the SRB (Long Lake) between 1900 and 1920. This is contemporaneous with similar enrichments observed in Lake CDA, as well as the completion of Long Lake Dam (1913). In the most downstream part of the basin (Spokane River Arm of Lake Roosevelt), enrichment began substantially later, between 1930 and 1940. The temporal difference in enrichment between Long Lake and the River Arm may reflect the latter's greater distance from the presumed source of the enrichment (the CDA River Basin); however, the difference is more likely the result of the completion of Grand Coulee Dam (1934–1941), which formed Lake Roosevelt, backed up the Spokane River, and increased water levels in the River Arm by about 30 m.
Formation of apatite on poly(α‐hydroxy acid) in an accelerated biomimetic process
Authors: Chen Yun , Mak Arthur F. T. , Li Jiashen , Wang Min , Shum Anita W. T.
Published: January 2005

Bonelike apatite coating was formed on poly(L‐lactic acid) films and poly(glycolic acid) scaffolds within 24 h through an accelerated biomimetic process. The ion concentrations in the simulated body fluid (SBF) were nearly 5 times of those in the human blood plasma. The apatite formed was characterized by using scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The apatite formed in 5SBFs was similar in morphology and composition to that formed in the classical biomimetic process using SBF or 1.5SBF and similar to that of natural bone. This indicated that the biomimetic apatite‐coating process could be accelerated by using concentrated simulated body fluid at 37°C. Besides saving time, the accelerated biomimetic process is particularly significant to biodegradable polymers. Some polymers that degrade too fast to be coated with apatite by a classical biomimetic process (e.g., PGA) could be coated with bonelike apatite in an accelerated biomimetic process. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 73B: 68–76, 2005
Presence of MUC4 in human milk and at the luminal surfaces of blood vessels
Authors: Zhang Jin , Perez Aymee , Yasin Mohammad , Soto Pedro , Rong Min , Theodoropoulos George , Carothers Carraway Coralie A. , Carraway Kermit L.
Published: January 2005

MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP‐1 (MUC4α) and a transmembrane subunit ASGP‐2 (MUC4β), which has been implicated in the protection of epithelial cell surfaces. Surprisingly, development and characterization of a new monoclonal antibody (mAb), called 1G8, against ASGP‐2 demonstrated by immunohistochemistry the presence of MUC4 at the luminal surfaces of blood vessels of both normal tissues and tumors. Muc4 was detected with 1G8 and other Muc4 antibodies in blood vessels from humans, rats and mice. This expression of MUC4 in endothelial cells was confirmed by immunoblotting with 1G8 in human umbilical vein endothelial cells (HUVECs), human iliac artery endothelial cells (HIAECs), and human microvascular endothelial cells (HMVECs). MUC4 could be observed on HUVECs grown on either plastic or Matrigel. Finally, MUC4 expression in the three types of endothelial cell lines was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR). These results provide, to our knowledge, the first demonstration of a member of the MUC gene family and membrane mucin in blood vessels. As a luminal surface component, the MUC4 is situated to contribute to the non‐adhesive luminal surface and to act as an intrinsic protection and survival factor. © 2005 Wiley‐Liss, Inc.
Hypoxia/reoxygenation reduces microvascular endothelial cell coupling by a tyrosine and MAP kinase dependent pathway
Authors: Rose Keeley , Ouellette Yves , Bolon Michael , Tyml Karel
Published: January 2005

Communication of electrical signals along the microvascular endothelium plays a key role in integrating microvascular function required for local regulation of blood flow. The aim of the present study was to examine the effect of a short‐term hypoxia (0.1% O2, 1 h) plus reoxygenation (H/R) on electrical coupling in cultured monolayers of microvascular endothelial cells (rat skeletal muscle origin). To assess coupling, we used a current injection technique and a Bessel function model to compute the intercellular resistance (an inverse measure of coupling) and cell membrane resistivity (a measure of resistance to current leakage across the cell membrane). H/R resulted in rapid (within 4 min after reoxygenation) and sustained (up to 100 min) reduction in intercellular coupling, but it did not alter membrane resistivity. H/R did not alter gap junction protein connexin 43 expression nor its tyrosine phosphorylation as determined by immunoblot and immunoprecipitation analyses. Inhibition of mitochondrial respiration (1 mM NaCN) did not mimic the effect of H/R. However, pre‐treatment of monolayers with tyrphostin A48 (1.5 μM), PP2 (10 nM) (tyrosine kinase inhibitors), U 0126 (20 μM), and PD 98059 (5 μM) (MEK1/2 inhibitors) inhibited the H/R‐induced reduction in coupling. These results indicate that endothelial cell coupling was reduced quickly after reoxygenation, via activation of a tyrosine and MAP kinase dependent pathway. We predict that a short‐term H/R can rapidly compromise microvascular function in terms of reduced cellular communication along the vascular wall. © 2005 Wiley‐Liss, Inc.
Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down‐regulation of transferrin receptor dependent iron uptake
Authors: Kang Jae Seung , Cho Daeho , Kim Young‐In , Hahm Eunsil , Kim Yeong Seok , Jin Shun Nu , Kim Ha Na , Kim Daejin , Hur Daeyoung , Park Hyunjeong , Hwang Young Il , Lee Wang Jae
Published: January 2005

Sodium ascorbate (vitamin C) has a reputation for inconsistent effects upon malignant tumor cells, which vary from growth stimulation to apoptosis induction. Melanoma cells were found to be more susceptible to vitamin C toxicity than any other tumor cells. The present study has shown that sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose‐ and time‐dependent fashion, indicating that intracellular iron levels may be a critical factor in sodium ascorbate‐induced apoptosis. Indeed, sodium ascorbate‐induced apoptosis is enhanced by the iron chelator, desferrioxamine (DFO) while it is inhibited by the iron donor, ferric ammonium citrate (FAC). Moreover, the inhibitory effects of sodium ascorbate on intracellular iron levels are blocked by addition of transferrin, suggesting that transferrin receptor (TfR) dependent pathway of iron uptake may be regulated by sodium ascorbate. Cells exposed to sodium ascorbate demonstrated down‐regulation of TfR expression and this precedes sodium ascorbate‐induced apoptosis. Taken together, sodium ascorbate‐mediated apoptosis appears to be initiated by a reduction of TfR expression, resulting in a down‐regulation of iron uptake followed by an induction of apoptosis. This study demonstrates the specific mechanism of sodium ascorbate‐induced apoptosis and these findings support future clinical trial of sodium ascorbate in the prevention of human melanoma relapse. © 2005 Wiley‐Liss, Inc.
Application of the TLM technique to integrated optic component modelling
Authors: Jacquin O. , Ndagijimana F. , Cachard A. , Benech P.
Published: January 2005

The TLM algorithm is of high interest to simulate new integrated optical devices as a ‘photonic band gap’ (PBG) structures. These components are realized with semiconductor material and constituted by a set of abrupt optical discontinuities. The electromagnetic behaviour of these structures does not allow the use of usual simulation methods of integrated optics. Indeed, their validity conditions are not satisfied. Then, we have to use unusual simulation method for integrated optics as TLM software which allows the visualization and understanding of the behaviour of electromagnetic field in the PBG structures. In this paper, the simulation results of different optical devices made from the TLM method are presented. Copyright © 2001 John Wiley & Sons, Ltd.
γ‐Glutamylcysteine ethyl ester protection of proteins from Aβ(1–42)‐mediated oxidative stress in neuronal cell culture: A proteomics approach
Authors: Boyd‐Kimball Debra , Sultana Rukhsana , Poon H. Fai , Mohmmad‐Abdul Hafiz , Lynn Bert C. , Klein Jon B. , Butterfield D. Allan
Published: January 2005

Protein oxidation mediated by amyloid β‐peptide (1–42) (Aβ[1–42]) has been proposed to play a central role in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with aging and the loss of cognitive function. The specific mechanism by which Aβ(1–42), the primary component of the senile plaque and a pathologic hallmark of AD, contributes to the oxidative damage evident in AD brain is unknown. Moreover, the specific proteins that are vulnerable to oxidative damage induced by Aβ(1–42) are unknown. Identification of such proteins could contribute to our understanding of not only the role of Aβ(1–42) in the pathogenesis of AD, but also provide insight into the mechanisms of neurodegeneration at the protein level in AD. We report the proteomic identification of two proteins found to be oxidized significantly in neuronal cultures treated with Aβ(1–42): 14‐3‐3ζ and glyceraldehyde‐3‐phosphate dehydrogenase. We also report that pretreatment of neuronal cultures with γ‐glutamylcysteine ethyl ester, a compound that supplies the limiting substrate for the synthesis of glutathione and results in the upregulation of glutathione in neuronal cultures, protects both proteins against Aβ(1–42)‐mediated protein oxidation. © 2005 Wiley‐Liss, Inc.
Inactivation of bad by site‐specific phosphorylation: The checkpoint for ischemic astrocytes to initiate or resist apoptosis
Authors: Chen Xiao Qian , Lau Lok Ting , Fung Yin‐Wan Wendy , Yu Albert Cheung Hoi
Published: January 2005

Bcl‐2‐associated death protein (Bad), a member of the Bcl family, directs astrocytes in primary cultures to enter or resist apoptosis during ischemia in vitro. Under ischemia, Bad was the only Bcl family member whose expression was upregulated significantly during the early stages of an ischemic insult. Increased endogenous Bad was translocated from the cytoplasm to mitochondria to induce apoptosis in astrocytes. Concurrently, ischemia also induced Bad phosphorylation specifically on Ser112 to promote survival. This site‐specific phosphorylation of Bad was mediated by an early activation of the mitogen‐activated protein kinase/extracellular signal‐regulated protein kinase (MAPK/ERK) intracellular signaling pathway. This study demonstrates that ischemia‐induced Bad plays a dual role in determining whether astrocytes enter or resist apoptosis after an ischemic insult. © 2005 Wiley‐Liss, Inc.
PLCγ signaling underlies BDNF potentiation of Purkinje cell responses to GABA
Authors: Cheng Qing , Yeh Hermes H.
Published: January 2005

Brain‐derived neurotrophic factor (BDNF) regulates neuronal survival, neurite outgrowth, and excitatory synaptic transmission. We reported recently that acute BDNF exposure decreased γ‐aminobutyric acid (GABA) responses in cultured mouse cerebellar granule cells through tyrosine receptor kinase B (TrkB) receptor‐mediated signaling. In the present study, we extend this work to investigate BDNF‐induced modulation of GABA responses and GABAA receptor‐mediated synaptic events in cerebellar slices. Thin (200 μm) parasagittal slices of cerebellum were prepared from postnatal Day 7 and 14 mice. Purkinje cells and granule cells, both of which express TrkB‐like immunoreactivity, were identified for whole‐cell recording. BDNF promptly enhanced GABA responses in Purkinje cells but, consistent with our previous finding in culture, attenuated those recorded in granule cells. In Purkinje cells, BDNF exposure shifted rightward the cumulative peak amplitude distribution for miniature inhibitory postsynaptic currents (mIPSCs) without changing the mIPSC frequency. BDNF‐induced potentiation of Purkinje cell responses to GABA was blocked by TrkB‐Fc (receptor body that sequesters BDNF), K252a (inhibitor of TrkB receptor autophosphorylation), U73122 (inhibitor of phospholipase‐Cγ [PLCγ]), KN62 (specific inhibitor of calcium/calmodulin‐dependent kinase), KT5720 (specific cyclic AMP‐dependent kinase inhibitor), and by intracellular dialysis of Rp‐cyclic AMP or BAPTA (1,2‐bis(o‐aminophenoxy)ethane‐N,N, N′,N′‐tetraacetic acid). Overall, our results indicate that BDNF acutely potentiates GABAA receptor function in cerebellar Purkinje cells via the TrkB receptor‐PLCγ signal transduction cascade. In addition, we propose that cyclic AMP‐mediated intracellular signaling mechanisms may facilitate manifestation of the BDNF‐induced modulatory outcome. © 2005 Wiley‐Liss, Inc.
Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system
Authors: Feng Jian , Chang Hua , Li En , Fan Guoping
Published: January 2005

To explore the role of DNA methylation in the brain, we examined the expression pattern of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the mouse central nervous system (CNS). By comparing the levels of Dnmt3a and Dnmt3b mRNAs and proteins in the CNS, we showed that Dnmt3b is detected within a narrow window during early neurogenesis, whereas Dnmt3a is present in both embryonic and postnatal CNS tissues. To determine the precise pattern of Dnmt3a and Dnmt3b gene expression, we carried out X‐gal histochemistry in transgenic mice in which the lacZ marker gene is knocked into the endogenous Dnmt3a or Dnmt3b gene locus (Okano et al. [1999] Cell 99:247–257). In Dnmt3b‐lacZ transgenic mice, X‐gal‐positive cells are dispersed across the ventricular zone of the CNS between embryonic days (E) 10.5 and 13.5 but become virtually undetectable in the CNS after E15.5. In Dnmt3a‐lacZ mice, X‐gal signal is initially observed primarily in neural precursor cells within the ventricular and subventricular zones between E10.5 and E17.5. However, from the newborn stage to adulthood, Dnmt3a X‐gal signal was detected predominantly in postmitotic CNS neurons across all the regions examined, including olfactory bulb, cortex, hippocampus, striatum, and cerebellum. Furthermore, Dnmt3a signals in CNS neurons increase during the first 3 weeks of postnatal development and then decline to a relatively low level in adulthood, suggesting that Dnmt3a may be of critical importance for CNS maturation. Immunocytochemistry experiments confirmed that Dnmt3a protein is strongly expressed in neural precursor cells, postmitotic CNS neurons, and oligodendrocytes. In contrast, glial fibrillary acidic protein‐positive astrocytes exhibit relatively weak or no Dnmt3a immunoreactivity in vitro and in vivo. Our data suggest that whereas Dnmt3b may be important for the early phase of neurogenesis, Dnmt3a likely plays a dual role in regulating neurogenesis prenatally and CNS maturation and function postnatally. © 2005 Wiley‐Liss, Inc.
Expression profiling of sciatic nerve in a Charcot‐Marie‐Tooth disease type 1a mouse model
Authors: ten Asbroek Anneloor L.M.A. , Verhamme Camiel , van Groenigen Marjon , Wolterman Ruud , de Kok‐Nazaruk Maryla M. , Baas Frank
Published: January 2005

Expression profiling was performed on sciatic nerve of normal mice and of transgenic mice overexpressing the peripheral myelin protein 22 kDa (PMP22). These mice represent a model for the hereditary peripheral neuropathy Charcot‐Marie Tooth type 1A. Comparison of the profiles reveals that the proteasomal degradation pathway and various signaling mechanisms are up‐regulated in the diseased nerve. The down‐regulated processes represent cell shape and adhesion as well as cellular activity and metabolism. In addition, we found that the most significantly up‐regulated differences could not be mapped on known transcripts and thus might represent not identified transcripts. Our data will be helpful to direct future research aimed at deciphering the molecular pathogenesis of the most prevalent hereditary peripheral neuropathy. © 2005 Wiley‐Liss, Inc.
Effect of tumor necrosis factor‐α on the reciprocal G‐protein‐induced regulation of norepinephrine release by the α2‐adrenergic receptor
Authors: Reynolds Jessica L. , Ignatowski Tracey A. , Spengler Robert N.
Published: January 2005

α2‐Adrenergic receptors control norepinephrine (NE) release and tumor necrosis factor‐α (TNF) production from neurons. TNF regulates NE release, depending on α2‐adrenergic receptor functioning. The relationship between TNF production in the brain and α2‐adrenergic receptor activation could have profound control over NE release. TNF and α2‐adrenergic regulation of NE release was investigated in rat hippocampal slices incubated with pertussis toxin (PTX). The α2‐adrenergic receptor couples to Gαi/o‐proteins to inhibit NE release; however, in slices preexposed to PTX, α2‐adrenergic receptor activation facilitates NE release. TNF exposure subsequent to PTX restores α2‐adrenergic inhibition of NE release. PTX exposure of hippocampal slices prevents agonist‐induced increases in Gαi/o labeling with a GTP analog; after subsequent TNF exposure, agonist‐induced increases in Gαi/o labeling are restored. TNF regulation of NE release transforms from inhibition to facilitation depending on α2‐adrenergic receptor activation following PTX exposure. Therefore, TNF directs the coupling of the α2‐adrenergic receptor, ultimately affecting NE release. © 2005 Wiley‐Liss, Inc.
Effects of an absenteeism feedback intervention on employee absence behavior†
Authors: Gaudine Alice P. , Saks Alan M.
Published: January 2005

The purpose of this study was to test the effects of an Absenteeism Feedback Intervention (AFI) on employee absenteeism. Three hundred and seventy‐one employees working in 14 experimental and 13 control groups in a medium sized hospital participated in the study. Employees working in the experimental groups received absenteeism feedback at three time periods that provided them with information about their own number of absent days and episodes (sequential days counted as a single absence episode) as well as the average of their work and occupational group. Comparisons of absent days and episodes between the AFI and control groups indicate some support for the effectiveness of the intervention. In particular, there was a reduction in absent days and episodes for employees with higher than average absenteeism during the previous year but who were not extreme offenders. The research and practical implications of the AFI for reducing employee absenteeism are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
ENSO variability, teleconnections and climate change
Authors: Diaz Henry F. , Hoerling Martin P. , Eischeid Jon K.
Published: January 2005

An overview is presented of the principal features of the El Niño–Southern Oscillation (ENSO) teleconnections in terms of regional patterns of surface temperature, precipitation and mid‐tropospheric atmospheric circulation. The discussion is cast in the context of variations in the associations over time, with decadal scale changes emphasized. In the five decades or so for which we have adequate records to reliably analyse the global aspects of ENSO effects on regional climates around the world, we have witnessed one major decadal scale change in the overall pattern of sea‐surface temperatures (SST) in the global ocean, and concomitant changes in the atmospheric response to those changes. The analysis underscores the connection between low frequency changes in tropical SST, ENSO and decadal scale changes in the general atmospheric circulation, pointing to the complex interplay between the canonical ENSO system, slow changes in SST in the Indo‐Pacific over the last century, and long‐term changes in the atmospheric circulation itself. Published in 2001 by John Wiley & Sons, Ltd.