Neutral endopeptidase depletion decreases colon cancer cell proliferation and TGF-B1 synthesis in indirect co-cultures with normal colon fibroblasts

Purpose Although recent studies have suggested that neutral endopeptidase (NEP) is implicated in the regulation of colon cancer (CC) cell growth and metastasis, the influence of the tumor microenvironment on this role of NEP has not been investigated so far. Normal colon fibroblasts (NCFs) constitute a component of the stroma surrounding a tumor in an early stage of its development. NCFs can influence transformed cells via different paracrine factors, including TGF-β1. This in vitro study was undertaken to evaluate the role of NEP in CC promotion in conditions of indirect co-culture of CC cells (LS180 and SW620) with NCFs (CCD-18Co) or their conditioned medium (CM-18Co). Methods We examined cell proliferation (with the BrdU assay) and invasiveness (using BME-coated inserts, 8 µm) of NEP-expressing, NEP-silenced (siRNA), and NEP-inhibited (with thiorphan, i.e. a NEP specific inhibitor) CC cells cultured alone or co-cultured with CCD-18Co or with their conditioned medium. The Western blot and ELISA methods were used to assess the level of TGF-β1. Results The results showed that the co-culture of the NEP-depleted CC cells with NCFs or their conditioned medium resulted in a significant decrease in cell proliferation in comparison with the proliferative potential of NEP-silenced/inhibited CC cells cultivated alone. In contrast, the NEP depletion did not influence the invasiveness of CC cells in the co-cultures. The co-culture of CC cells with CCD-18Co or CM-C18Co resulted in increased synthesis of TGF-β1, while the NEP downregulation decreased the synthesis of TGF-β1 in CC cells and abolished the stimulatory effect of the co-cultures on TGF-β1 production. Conclusions The results suggest that the expression of NEP by colon cancer cells is essential for their proliferation and TGF-β1 synthesis during paracrine interactions with NCFs (AU)

Peak nasal inspiratory flow in children with allergic rhinitis. Is it related to the quality of life?

INTRODUCTION AND OBJECTIVES: Allergic rhinitis (AR) is the most common allergic disease in childhood. Nasal obstruction is a typical symptom of AR, however, its quantification by clinical examination is difficult. To provide an objective assessment of nasal patency, the peak nasal inspiratory flow (PNIF) is used. Symptoms of AR have a noticeable impact on the quality of life. The aim of this study was to assess which factors may have an impact on PNIF values and to evaluate the possible relationships between PNIF and QoL in children with AR. Patients and METHODS: We recruited patients aged 6-17 years (n = 208, 89 girls and 119 boys) with AR. All children underwent PNIF measurements. Parents and children completed KINDL-R generic questionnaires, to assess the quality of life of the children. RESULTS: The average PNIF value was 98.9 ± 37.4 L/min. A very strong (p < 0.001) relationship between the PNIF value and height, age and weight of the child was observed. The sex of the patient has no influence on the PNIF value. We showed that PNIF values significantly increased with each attempt. The children assessed their QoL at 45.6 ± 8.5 points in the KINDL-R questionnaire and the parents rated their children's QoL at 73.7 ± 10.7 points. We observed a weak negative correlation between PNIF and the QoL based on the parents' assessment and the child's self-assessment. CONCLUSIONS: PNIF values depend mostly on height, but also on the child's age and weight. A learning effect (significant increase in PNIF upon each attempt) was shown. Higher PNIF does not improve the QoL

No disponible

Serum level of cathelicidin LL-37 is increased in euthymic patients with bipolar disorder irrespective of their cardio-metabolic status

Abstract Background Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in patients with bipolar disorder. Objectives The aim of this study is to re-evaluate serum LL-37 levels in patients with euthymic bipolar disorder and in healthy controls, matched for anthropometric and body composition parameters. Methods 36 adult patients with euthymic bipolar disorder and 68 non-depressed adults were included into the study. Concentration of LL-37 in serum was assessed using ELISA method. Detailed anthropometric measurements, body composition and biochemical analyses were performed. Results There was a statistically significant difference (p = 0.01) in serum LL-37 level between patients with bipolar disorder (4.97 ± 7.98 ng/mL) and control subjects (1.78 ± 2.69 ng/mL). Discussion Results of this study indicate that LL-37 serum level is increased in euthymic bipolar disorder patients. We found that this increase could not be attributed to analyzed anthropometric or body composition parameters.

Microbiome in the primary prevention of allergic diseases and bronchial asthma

Tremendous progress in the ability to identify and test the function of microorganisms in recent years has led to a much better understanding of the role of environmental and host microbiome in the development of immune function, allergic sensitization and asthma. In this review, the most recent findings on the relationships between environmental microbiota, respiratory, intestinal microbiome, the consequences of early-life microbial exposure type and gut-lung microbial axis and the development of asthma and atopy are summarized. The current perspective on gut and airway microbiome manipulation for the primary prevention of allergic diseases and asthma is also discussed

No disponible

[Communication, language and the brain: from past anterior to near future]. / Communication, langage et cerveau : du passé antérieur au futur proche.

The goal of this article is to share some reflection on the astonishing evolution of the ideas in communication neuroscience and neurolinguistics over the last 30 years, since the founding of the société de neuropsychologie de langue française. in particular, a number of conceptual and methodological advancements have characterized this period, many of which have been lead or heavily contributed by french-speaking research groups in that field. among the advances discussed, are (a) the widening to discourse and pragmatic components of the concept of language, as well as the theoretical and clinical implication of this conceptual extension, (b) the unique contribution of anatomical and functional neuroimaging, (c) the massive impact of the cognitive revolution on theoretical frameworks of language components, and its influence on therapy, (d) the disappearance and the re-appearance of the brain in the main stream research on language over this period, (e) the new perspectives offered though attention put on social aspects of language and the social participation of the individual with language disorders, (f) the emergence of a genuine science of aphasia rehabilitation, and (g) the rediscovery of inter-individual characteristics both genetically- and environmentally- determined. The authors then risk themselves in trying to envision what could characterize the evolution in the field for the next 30 years. Though perilous, this speculative exercise allowed to pinpoint to a number of anticipated advancements including (a) a probable reconciliation between cognitive and connectionist models to the benefit of both visions, (b) an increased contribution of social and emotional neurosciences, (c) some inescapable technological advancements, including light portable neuroimaging devices which will allow to study the neurobiological bases of communication in natural contexts, (d) the integration between communication and aging in cognitive neuroscience and (e) the development of new research fields at some unexpected cross-roads (e.g., physical activity and communication ?) as well as the description of new types of aphasia (e.g., towards a chat aphasia !). Taken together, the advancements made over the 30 last years, and the perspective of future development, confirms the premier role of cognitive neuroscience of language and neurolinguistics in setting the pace through innovative approaches that allow unveiling the mysteries of the mutual relationships between brain and cognition.

[A subjective evaluation of epibulbar and etrobulbar anesthesia in cataract phacoemulsification]. / Sub''ektivnaia otsenka metodov epibul'barnoi i retrobul'barnoi anestezii pri fakoemul'sifikatsii katarakty.

Described in the paper are comparative descriptions of the efficiency of epibulbar and retrobulbar anesthesia made through evaluating the sensation of pain experienced by patients in cataract phacoemulsification and IOL implantation. The patients (1046 subjects, aged 28 to 89) were shared between 2 groups; they received an identical premedication by midazolam, peroral administration, 3.75 mg in 1 h before surgery. Epibulbar anesthesia with 1% proximetacaine hydrochloride, administered via instillator, was used in Group 1 (524 patients). Analgesia with 2% lidocaine hydrochloride solution (injections, 1:1) was made in Group 2 (522 patients). The subjective pain sensations experienced by patients during subsequent surgical stages were evaluated by an international 6-point scale. The pain sensations were found to vary from 0 to 4 points (mean point value--2.25) in Group 1. The most severe pain was experienced by the patients during the introduction of the phacoemulsificator tip into the anterior chamber of the eye (mean pain value--1.75 points) as well as during IOL implantation (mean pain value--1.25). The instillator-based analgesia does not normally provoke any complications and is well tolerated by patients; it can be recommended for cataract phacoemulsification.

Effects of peak concentrations on the neurotoxicity of styrene in volunteers.

The manufacture of fibreglass reinforced plastic products may give rise to substantial peak exposures to styrene. Such exposure patterns need further consideration in terms of styrene neurotoxicity. The aim of this study was to evaluate the neurotoxic effects of short-term peak exposures in volunteers, at levels respecting the Quebec occupational exposure limits (8 hours time weighed average of 213 mg/m3 and 15 min average of 426 mg/ m3). The volunteers had not been previously exposed to styrene and they had no documented exposure to known neurotoxicants during the study. Twenty-four volunteers were exposed to five exposure scenarios during 6 hours: a, stable exposure to 106 mg/m3; b, variable exposure with a mean concentration of 106 mg/m3 with four 15 min peaks mounting up to 213 mg/m3; c, stable exposure to 213 mg/m3; d, variable exposure with a mean concentration of 213 mg/m3 and four peaks of 426 mg/m3 and e, two stable exposures to 5 mg/m3 (control). Before and after each exposure scenario, volunteers were submitted to a battery of sensory tests (visual and olfactory), neuropsychological tests (reaction time, attention, memory, psychomotor function), and self-evaluation questionnaires (mood and symptoms) in a test-retest design. The results show that the different exposure scenarios involving peak exposures did not influence either the performance to any test or subjective signs and symptoms. However, due caution must be exercised in extrapolation of the current results to occupational exposure since only acute exposures were tested and volunteers were at rest during exposure, which resulted in lower doses than those experienced by physically active workers.

Production of narratives: picture sequence facilitates organizational but not conceptual processing in less educated subjects.

Fifty-three healthy older adults were produced stories induced by two types of picture stimuli (single picture and picture sequence). Discourse samples were analyzed for: (1) percentage of expected main ideas (which reflect conceptual processing) and (2) number of transitional markers (which reflect organizational processing). Results indicate that the older group (75 to 84 years) produced a lower percentage of main ideas and less transitional markers than the younger group (65 to 74 years). Both groups also showed better performance in response to the picture sequence than to the single picture. For the percentage of expected main ideas, however, a superior performance in response to the picture sequence was observed only among older subjects with higher (11 to 18 years) but not lower (4 to 10 years) levels of formal education. The role of education and the importance of stimulus type in discourse-specific tasks are discussed.

Employee reactions to the introduction of a bulk food distribution system in a nursing home.

Decentralized bulk food distribution was implemented in a nursing home. Employees working with elderly residents with dementia were asked their opinion of the impact of the new system on residents and workload. A convenience sample of 24 employees (57% of the staff) completed a 31-item, self-administered Likert-scale questionnaire that allowed open-ended comments. Responses were subjected to descriptive quantitative analysis, and a qualitative approach was used to explore themes that emerged in comments. Qualitative analysis indicated that 52% of responses were negative in tone, 30% were positive, and 18% were neutral. Initially, three categories of comments emerged, with specific multiple themes related to the residents (41%), the employees (37%), or the food-service system (22%). Most comments in the employee category were negative, and suggested that the decentralized food-service system caused hardship for the staff. This problem was resolved by adding one staff-hour at the midday meal. One year later, an abbreviated repeat survey of 29 employees revealed adaptation and general acceptance of the system. Because a motivated patient care staff is essential to the successful feeding of nursing home residents with dementia, employees' concerns must be considered when operational changes are planned.

Key dimensions of client satisfaction with assistive technology: a cross-validation of a Canadian measure in The Netherlands.

The purpose of this study was to conduct a cross-validation of the bidimensional structure of a satisfaction measure with assistive technology. Data were drawn from a follow-up study of 243 subjects who had been administered the Dutch version of the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST). Ratings related to 12 satisfaction items were analysed. Factor analysis results showed that the underlying structure of satisfaction with assistive technology consists of two dimensions related to assistive technology, Device (eight items) and Services (four items), accounting for 40% of the common variance. This finding was consistent with a previous Canadian study and was interpreted as supporting the adequacy and stability of the QUEST measure of satisfaction. Although the structure is delineated, further studies are recommended to support its use in European countries.

[Plurality of patterns of cognitive impairment in normal aging and in dementia]. / Pluralité des patrons d'atteinte cognitive accompagnant le vieillissement normal et la démence.

Normal aging, as well as most of the degenerative diseases of the central nervous system characterizing old age, have an impact on cognitive abilities which are obvious as well as increasingly understood. Cognitive changes in normal ageing realize a plurality of possible patterns of cognitive disabilities. Dementias are also well known to be characterized by a plurality of cognitive impairments patterns. The different cognitive patterns are likely to be due to distinct levels of impairments of different domains of cognition, or of different components within one given domain of cognition. These differences are such that in some cases they can even realize double dissociations. The plurality of cognitive impairments patterns in normal aging and in dementia will be discussed as well as the different factors that could contribute to such a plurality. Some of these factors relate to pre-morbid characteristics of the individuals known to influence the functional organization of the brain for cognition. Others--of major importance--are related to the nature and the distribution of the pathophysiological processes underlying normal ageing or a given degenerative disease. It is also reminded that some or many of these factors can interact with more general cognitive factors, such as speed of execution. It is however suggested that, despite of their presence, these general factors partly contribute to the cognitive impairments in neurodegenerative dementia. In this case, the impact of different disease-related factors over a general cognitive factor is probably much greater than in the case of normal aging.

Conceptual apraxia and semantic memory deficit in Alzheimer's disease: two sides of the same coin?

This study was designed to examine the patterns of apraxic disturbances and the relationships between action knowledge and other measures of semantic knowledge about objects in 10 well-characterized Alzheimer's disease (AD) patients. Five tasks were used to assess components of action knowledge (action-tool relationships, pantomime recognition, and sequential organization of action) and praxis execution (actual use, pantomiming) according to the cognitive model of praxis. Three tasks (verbal comprehension, naming, and a visual semantic matching task) were used to assess verbal-visual semantics. Considering patterns of apraxia first, conceptual apraxia was found in 9 out of the 10 AD patients, suggesting that it is a common feature even in the early stages of AD. Second, we found partly parallel deficits in tests of action-semantic and verbal-visual semantic knowledge in 9 AD patients. Impaired action knowledge was found only in patients with a semantic language deficit. These findings provide no evidence that "action semantics" may be separated from other semantic information. Our results support the view of a unitary semantic system, given that the representations of action-semantic and other semantic knowledge of objects are often simultaneously disrupted in AD.

Relationships between acid-soluble thiol peptides and accumulated Pb in the green alga Stichococcus bacillaris.

Stichococcus bacillaris, an ubiquitous green microalga accumulated inorganic lead (Pb) from aqueous solutions extra- and intracellularly. In response to Pb uptake acid-soluble thiol peptides (glutathione - GSH and phytochelatins - PC) were synthesized. The proportion of the intracellular Pb uptake by algal cells was low and comprised only 3-6% of the total metal sorption. The intracellular uptake was dependent on external Pb concentration, time of metal exposure and cell metabolism. Pb accumulation in alga was determined by means of 210Pb radiometry. Reduced GSH and PC were determined in algal cells using HPLC with the post-column derivatization with Ellman's reagent. Within the studied concentration range 0.1-20 µM, inorganic lead caused a significant production of induced thiol peptides: PC (n=2-4) and some other unidentified oligopeptides, probably (GluCys)n. The time of appearance and the concentration of individual oligomers of phytochelatins were dependent on the external Pb concentration and time of metal exposure. In algal cells exposed to Pb, significant changes in the GSH level accompanying the formation of the induced thiol peptides were also observed. The GSH level decreased in the cells exposed to the lower (up to 10 µM) studied Pb concentrations or increased in the cells treated with higher (20 µM) Pb concentrations. The thiol groups originated from induced peptides (mainly phytochelatins) followed a stoichiometric relationship 2:1 to the intracellular Pb amounts, however, only at the lowest studied external concentration (0.1 µM). At higher concentrations (up to 2.5 µM), intracellular Pb concentration was equal or even exceeded (at Pb>2.5 µM) two to three times the level of induced thiols. S. bacillaris accumulated intracellularly by 46% more Pb in light than in dark and the level of induced thiol peptides was significantly higher in the cells exposed to Pb under illumination. The rapid formation of these peptides in S. bacillaris in response to Pb, and their elimination (by about 90%) when algae were placed into the Pb-free solution reveal a tight regulation of GSH and phytochelatin pools in the algal cells exposed to toxic metals. The obtained results suggest that both PCs and GSH are the primary line of defence against the Pb toxicity. Additionally, the induced thiol peptides in S. bacillaris could be a good indicator of intracellular Pb availability and stress at the metal concentrations found in polluted fresh waters.

Pantomime recognition impairment in Alzheimer's disease.

This study was designed to examine whether 10 AD patients with diffuse lesions and an early semantic deficit could comprehend the meaning of pantomimes and symbolic gestures. We especially wanted to determine the relationship between pantomime recognition and production. The tasks involved naming or showing an understanding (e.g., circumlocutions) of the pantomimes executed by the examiner and producing pantomimes to verbal command or to imitation. The results showed no significant relationship between pantomime comprehension and pantomime production. However, 60% of AD patients performed poorly compared to controls on the Gesture Recognition task. Gesture comprehension was highly correlated with a measure of global cognitive impairment (3MS). The data are consistent with the proposed separation of comprehension and action production systems in a cognitive model of praxis. Gesture comprehension may be diffusely distributed and thus preserved in the early stages of AD as in circumscribed lesions of the left parietal lobe.

Item analysis of the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST).

The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) is an outcomes assessment tool designed to measure satisfaction with assistive technology in a structured and standardized way. The purpose of this article is to present the results of an analysis of the 24 items comprising QUEST and to explain how a subset of items demonstrating optimal measurement performance was selected. The criteria against which the items were measured were general acceptability, content validity, contribution to internal consistency, test-retest stability, and sensitivity. The items that ranked best in terms of these measurement properties were submitted to factorial analysis in order to complete the item selection. The first series of analyses reduced the item pool approximately by half, and the second series of analyses led to the final selection of 12 items. Factor analysis results suggested a bidimensional structure of satisfaction with assistive technology related to the assistive technology device (eight items) and services (four items). The 12-item revised version that will result from this study should prove to be a reliable and valid instrument for measuring outcomes in the field of assistive technology.

Cognitive processing of drawing abilities.

This critical review examines constructional apraxia from a cognitive neuropsychological perspective. To our knowledge, van Sommers (1989) is the only researcher to present a global cognitive model of drawing abilities. He organizes it into two hierarchical systems: Marr's model of visual perception and a graphic production system. The latter comprises four hierarchically organized components: depiction decisions, production strategy, contingent planning, and articulatory and economic constraints. Van Sommers' model will be discussed in light of other models and on the basis of empirical neuropsychological studies (Farah, 1984; Kosslyn & Koenig, 1992; Roncato, Sartori, Masterson, & Rumiati, 1987; van Sommers, 1989). We find that: (1) the Kosslyn and Koenig visual perception model describes more accurately the perceptual components underlying copying than the visual perception system of van Sommers' drawing model, (2) Van Sommers' arguments in favor of a depiction processing as opposed to visual imagery are not convincing, (3) Van Sommers' assumption that a production strategy is a component is unclear, and (4) articulatory and economic constraints are not cognitive components, but constraints imposed during action programming. This literature review leads to a discussion of future research topics and the specificity of constructional apraxia.

Comparative study of oral and written picture description in patients with Alzheimer's disease.

Oral and written picture descriptions were compared in 22 patients with Alzheimer's disease (AD) and 24 healthy elderly subjects. AD patients had a significant reduction of all word categories, which, similarly to controls, was more pronounced in written than in oral texts. They also reported fewer information units than controls, but without task difference. At the syntactic level, written descriptions of AD subjects were characterized by a diminution of subordinate clauses and a reduction of functors. More grammatical errors were present in written descriptions by AD and control subjects. AD and control groups produced an equivalent number of semantic errors in both tasks. However, in oral description, AD patients had more word-finding difficulties. In sum, AD descriptions were always shorter and less informative than control texts. Additionally, written descriptions of AD patients appeared shorter and more syntactically simplified than, but as informative as oral descriptions. Whereas no phonemic paraphasias were observed in either group, AD patients produced many more graphemic paragraphias than controls produced. Furthermore, written descriptions had more irrelevant semantic intrusions. Thus, as compared to oral descriptions, written texts appeared to be a more reliable test of semantic and linguistics difficulties in AD.

Development of the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST).

This study's purpose was to develop a clinical instrument designed to evaluate user satisfaction with assistive technology devices. This paper describes the methodology used to develop the instrument entitled the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST). Based on the theoretical and practical foundations of assistive technology as well as on the concept of satisfaction, preliminary versions of the instrument were created and examined by a panel of team participants. After the panel's recommendations were incorporated, a pretest of the revised instrument was conducted and the final French version of QUEST emerged. The originality of QUEST lies in its inter-activeness and user-directed approach to assessing satisfaction with assistive technology. From a set of 27 variables, the user is asked to indicate the degree of importance he/she attributes to each of the satisfaction variables and then to rate his/her degree of satisfaction with each of the variables considered (quite or very) important. While QUEST remains a clinical instrument undergoing pilot testing, it holds much promise in our quest for a reliable and valid means of assessing assistive technology outcome from the user's perspective.

[Cognitive heterogeneity in Alzheimer's disease]. / Heterogeneidade cognitiva na doença de Alzheimer.

The authors describe and discuss neuropsychological aspects related to the functional organization of the brain connected to cognition in 81 Alzheimer's disease patients in the Laboratoire Théophile-Alajouanine du Centre de Recherche du Centre hospitalier Côte-des-Neiges in the University of Montreal. They confront the clinical of homogeneity against the heterogeneity within functional organization of the brain. The criteria used for diagnosis were those of the NINCDS-ADRDA. All of the patients were in the beginning of the evolution, in stages 3 and 4 of Reiberg (Functional Assessment Staging, FAST). The conclusion shows that there are two cognitive profiles: a non-recurrent profile, made up by the majority of the patients, and the heterogeneity depends on the genetic background of each individual; a recurrent profile, made up by a small group of patients that show changes in the heterogeneity of clinical, nosological, pathological and normal aging forms.

[Adequate neuropsychological evaluation of dementia]. / Avaliação neuropsicológica adequada às demências.

The authors discuss the protocol of the Optimal Neuropsychological Evaluation of Dementias of Montreal and its possible application in Brazil. This protocol is important for evaluation in neuropsychological evolution of dementia of the Alzheimer type and for bringing to the fore distinct affected cognitive profiles as much on a transversal base as longitudinal. The authors believe that its application would contribute to the progress of research in neurology, as in the clear distinction between normal aging and pathological aging.