Insulin-like growth factor binding proteins: regulation in chronic active plaques in multiple sclerosis and functional analysis of glial cells

Studies in experimental allergic encephalomyelitis, an animal model of multiple sclerosis (MS), suggest that astrocyte-secreted insulin-like growth factor binding protein-2 (IGFBP-2) helps target IGF-1 to IGF-1 receptor-expressing oligodendrocytes and promote remyelination. We examined the presence of IGFBPs 1-6 in astrocytes in normal post-mortem human brain tissue and lesions of MS by means of immunohistochemistry. Under normal conditions all six IGFBPs were detected. Compared to controls, hypertrophic astrocytes at the borders of chronic active MS lesions displayed increased immunoreactivity for IGFBP-2 and IGFBP-4. In vitro studies were performed to analyse the effects of IGFBPs on cellular proliferation of neonatal rat glial cells. Treatment of astrocytes with IGF-1 and -2 enhanced proliferation whereas IGFBP-2 and -4 inhibited cellular growth. Interestingly, combined treatment with IGFBP-2 and IGF-1 potentiated effects on cellular proliferation whereas combined treatment with IGFBP-2 and IGF-2 inhibited growth. Unlike IGFBP-2, IGFBP-4 inhibited proliferation in combined treatment with IGF-1. In contrast, combined treatment with IGFBP-2 and IGF-1 resulted in decreased cell survival of oligodendrocyte precursor cells. Our results suggest that the up-regulation of IGFBP-2 in reactive astrocytes in MS lesions may primarily serve to enhance the IGF-1-mediated mitogenic stimulus for astrocytes rather than supporting oligodendrocyte survival.     

Age-related evolution of amyloid burden, iron load, and MR relaxation times in a transgenic mouse model of Alzheimer's disease

T1 and T2 magnetic resonance relaxation times have the potential to provide biomarkers of amyloid-beta deposition that could be helpful to the development of new therapies for Alzheimer's disease. Here, we measured T1 and T2 times as well as plaques and iron loads in APP/PS1 mice, which model brain amyloidosis, and control PS1 mice. Iron was mostly associated with amyloid deposits in APP/PS1 animals, while it was diffuse in the PS1 mice. T1 was negatively correlated with age in most structures in APP/PS1 animals. This may be related to the age-associated myelin loss described in APP/PS1 mice rather than to amyloid deposition. T2 in the subiculum of adult APP/PS1 animals was lower than in PS1 mice, which may be related to the very high amyloid and iron loads in this region. T2 in the subiculum could thus serve as an early marker of the amyloid pathology.     

Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: report of 6 cases and systematic review of the literature

Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown etiology that affects multiple organs. We report 6 cases of ECD with neurological involvement and neuroradiological abnormalities on brain MRI. A literature review revealed 60 other cases of ECD with neurological involvement. We therefore analyzed 66 ECD patients with neurological involvement. Cerebellar and pyramidal syndromes were the most frequent clinical manifestations (41% and 45% of cases), but seizures, headaches, neuropsychiatric or cognitive troubles, sensory disturbances, cranial nerve paralysis or asymptomatic lesions were also reported. Neurological manifestations were always associated with other organ involvement, especially of bones (at least 86%) and diabetes insipidus (47%). Neurological involvement was responsible for severe functional handicaps in almost all patients and was responsible for the death of 6 of the 66 patients (9%). Neuroradiological findings could be separated into three patterns: the infiltrative pattern (44%), with widespread lesions, nodules or intracerebral masses, the meningeal pattern (37%), with either thickening of the dura mater or meningioma-like tumors, and the composite pattern (19%), with both infiltrative and meningeal lesions. Received in revised form: 21 October 2005     

Adjustment to community residential settings over time among older adults with serious mental illnesses

This exploratory cross-sectional study examined adjustment over time of three groups of seniors with serious mental illnesses (N=33), who were transferred from a psychiatric hospital to a community residential facility from 1995-1998. The study participants had lived in the community for 6-41 months. Outcomes included measures of global, social, cognitive and ADL functioning, quality of life and rehospitalizations. Analyses revealed no significant deterioration in symptomatology, cognitive and ADL functioning between groups and a significant change in social functioning. Five participants were readmitted for short hospitalizations. Participants in all groups expressed a positive quality of life in their current community residence.     

Cardiac channelopathy causing sudden death as revealed by molecular autopsy

Background

Mutations in cardiac ion channel genes have been identified to cause sudden unexplained deaths (SUD), and polymorphisms have also been suggested to be risk factors. Therefore, postmortem genetic testing has become an important tool in elucidating the cause of death.

Methods and results

In a sudden death case, a LQT-3-associated mutation (Il768V) in the cardiac sodium channel gene SCN5A was detected beside the common polymorphism H558R which is known to mitigate the effect of mutations in the gene. Both sequence variations were heterozygous. Large number of intervening base pairs make it impossible to identify whether they were located in cis or trans. Functional consequences of both variants were characterized after expressing different cRNAs in Xenopus oocytes by voltage clamp measurements. Western blot analysis indicates that the cis configuration of both variants may lead to a null allele. Since the woman had received an injection of Ultracain®, the potential effect of this drug was tested. In a trans configuration of both variants, the mutant channel exhibited an increase susceptibility of at least 10% for blocking with the drug articaine. Another novel finding is that the midpoint of activation in the case of the mutant channel is leftward shifted of at least ?10 mV.

Conclusion

The results of the study suggest that postmortem molecular screening is an important tool to elucidate the cause of SUD and that the administration of a drug and a functional interaction between polymorphisms and ion channel mutations may trigger the risk for sudden death.     

The Caregivers Quality of Life Cancer index scale (CQoLC): an exploratory factor analysis for validation in French cancer patients’ spouses

Purpose

The purpose of this study was to evaluate the reliability and validity of the Caregivers Quality of Life Cancer index scale (CQoLC) in a sample of spouses of French cancer patients.

Methods

The CQoLC, the Medical Outcomes Study Short Form 12 (MOS SF-12) and the State-Trait Anxiety Inventory (STAI) were administered to 300 spouses aged 21–85 years. Clinical data such as severity of cancer, medical treatment and duration of illness were obtained from a review of medical records.

Results

An exploratory factor analysis yielded a 23-item measure with one factor explaining 38.76% of the variance: labeled impairment of quality of life. The correlations between this factor and MOS SF-12 were negative for the physical component (ρ = ?0.351, p < 0.001) and positive for the mental component (ρ = 0.184, p < 0.005). One-way ANOVA with STAI scores indicated good discriminant validity (F[2, 237] = 4.80, p < 0.01, η² = 0.04). Participants with low anxiety had a better quality of life than those with moderate and high anxiety.

Conclusions

The findings indicate that the CQoLC has sufficient validity and reliability to assess the impairment of quality of life in spouses of French cancer patients.     

Antifungal Activity of 10 Guadeloupean Plants

Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. Copyright © 2012 John Wiley & Sons, Ltd.     

Recently Hospital-Discharged Older Adults Are Vulnerable and May Be Underserved by the Older Americans Act Nutrition Program

The home-delivered meal (HDM) program of the Older Americans Act Nutrition Program (OAANP) has traditionally served frail homebound older adults; however, due to gaps in the continuum of care, enrollment in this program following hospital discharge remains a challenge. Trained interviewers at 6 HDM sites in 6 U.S. states assigned 566 hospital-discharged individuals, ages 60–96 years, into either early (48 hour) or delayed (2 weeks) enrollment groups and assessed their health and nutrition status. Regardless of elapsed time at enrollment, more than 80% reported at least one limitation in activities and instrumental activities of daily living. About 20% had impaired cognition and more than 40% had depressive symptoms. Also, 40% reported fair or poor appetite. Despite intense recruitment from hospitals, only 30% ofparticipants were referred from hospitals. The recently hospital-discharged older adult population may include a higher prevalence of individuals with poor functional status and at nutritional risk than participants in the OAANP HDM program and yet may be underserved by this program.     

Cross-Border Use of Food Databases: Equivalence of US and Australian Databases for Macronutrients

When estimating dietary intake across multiple countries, the lack of a single comprehensive dietary database may lead researchers to modify one database to analyze intakes for all participants. This approach may yield results different from those using the country-specific database and introduce measurement error. We examined whether nutrient intakes of Australians calculated with a modified US database would be similar to those calculated with an Australian database. We analyzed 3-day food records of 68 Australian adults using the US-based Nutrition Data System for Research, modified to reflect food items consumed in Australia. Modification entailed identifying a substitute food whose energy and macronutrient content were within 10% of the Australian food or by adding a new food to the database. Paired Wilcoxon signed rank tests were used to compare differences in nutrient intakes estimated by both databases, and Pearson and intraclass correlation coefficients measured degree of association and agreement between intake estimates for individuals. Median intakes of energy, carbohydrate, protein, and fiber differed by <5% at the group level. Larger discrepancies were seen for fat (11%; P<0.0001) and most micronutrients. Despite strong correlations, nutrient intakes differed by >10% for an appreciable percentage of participants (35% for energy to 69% for total fat). Adding country-specific food items to an existing database resulted in similar overall macronutrient intake estimates but was insufficient for estimating individual intakes. When analyzing nutrient intakes in multinational studies, greater standardization and modification of databases may be required to more accurately estimate intake of individuals.     

Using Cognitive and Affective Illustrations to Enhance Older Adults’ Website Satisfaction and Recall of Online Cancer-Related Information

This study examined the effect of adding cognitive and affective illustrations to online health information (vs. text only) on older adults’ website satisfaction and recall of cancer-related information. Results of an online experiment among younger and older adults showed that illustrations increased satisfaction with attractiveness of the website. Younger adults were significantly more satisfied with the comprehensibility of the website than older adults, whereas older adults were more satisfied with perceived emotional support from the website than younger adults. Being more emotionally satisfied with the website led to greater recall of information for older adults, but not for younger adults. Illustrations can be used to enhance older adults’ website satisfaction and consequently recall of online cancer-related information.