Immunopathology and treatments of Guillain-Barré syndrome and of chronic inflammatory demyelinating polyneuropathy

The concepts of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) have changed over the last decade. The spectrum of GBS ranges from acute inflammatory demyelinating polyneuropathy to pure motor, sensory-motor or bulbar variants and the Miller Fisher syndrome. Also CIDP includes different variants in addition to the typical clinical picture with symmetrical proximal and distal weakness, such as a form with predominant distal weakness, a pure sensory form, an asymmetric form and a form with predominant cranial nerve involvement. Detailed immunopathologic features have been described in GBS and CIDP: most current investigations are centered on the hypothesis of molecular mimicry in GBS and together with the pathogenic role of cell-mediated immunity different antibodies have been discovered in GBS which interfere with nerve impulse conduction on neuromuscular transmission. The immunopathogenesis of CIDP remains fragmentary and insufficient for a unified hypothesis. Activated macrophages and T-cells with the participation of T-1 helper cell related cytokines seem to play a fundamental role in demyelination. The nature of antigen presenting cells, T-cell receptors, adhesion molecules and the proinflammatory cytokines need to be explored to design more specific immunotherapies. Established treatments in GBS include intravenous immunoglobulin and plasma exchange. Randomized trials have shown the efficacy of prednisone, intravenous immunoglobulin and plasma exchange in CIDP. New insight in the pathogenetic role of the cytokine-network in CIDP opens new therapeutical possibilities with the modification of the T-1 helper cell reaction with interferon.     

Injury of mitochondria and the expressions of fas and bax mRNA in the hippocampus of epileptic rats of different latency

IN T R O D U C T IO N M itochondria provide cells energy through oxidative phosphorylation by m eans of ATP. Biochem icalevidence indicates that m ost ATP consum ptions in brain are used forthe electric activity ofneurons, so the sufficientenergy supply f…     

Perception of patients’ unpredictability and beliefs on the causes and consequences of schizophrenia

Abstract.Background: The belief that mental disorders involve a high risk of unpredictable behaviours is a factor which influences negatively the social acceptance of the mentally ill. In this paper, we compare the beliefs about the causes and psychosocial consequences of schizophrenia expressed by 536 respondents who had the firm conviction that patients with schizophrenia are unpredictable and by 457 respondents who firmly believed that they are not.Methods: The survey was conducted in 30 Italian geographic areas, randomly selected taking into account their location and population density. The data were collected by the Questionnaire about Opinions on Mental Illness (QO).Results: Respondents who believed that patients with schizophrenia are unpredictable reported more frequently factors such as use of alcohol and drugs and frequenting bad company as being involved in the development of the disorder. In addition, this group showed more restrictive opinions about patients civil and affective rights. Low education was found to be significantly associated with perception of unpredictability in schizophrenia.Conclusions: These results suggest the need to: a) inform the general public on the main clinical characteristics of schizophrenia and on the risk of unpredictable behaviours in the acute phases of this mental disorder; b) carry out sensitisation campaigns against discrimination toward people with schizophrenia emphasising successful experiences of social integration.     

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Title： It should reflect the scientific value of the study exactly and the language should be precise and peculiar. The concrete revise advices should be suggested if the title is not in accordance with the standards.     

Comparison of the behavioural and histological characteristics of the 6-OHDA and α-synuclein rat models of Parkinson's disease

Development of relevant models of Parkinson's disease (PD) is essential for a better understanding of the pathological processes underlying the human disease and for the evaluation of promising targets for therapeutic intervention. To date, most pre-clinical studies have been performed in the well-established rodent and non-human primate models using injection of 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). Overexpression of the disease-causing protein α-synuclein (α-syn), using adeno-associated viral (AAV) vectors, has provided a novel model that recapitulates many features of the human disease. In the present study we compared the AAV-α-syn rat model with models where the nigro-striatal pathway is lesioned by injection of 6-OHDA in the striatum (partial lesion) or the medial forebrain bundle (full lesion). Examination of the behavioural changes over time revealed a different progression and magnitude of the motor impairment. Interestingly, dopamine (DA) neuron loss is prominent in both the toxin and the AAV-α-syn models. However, α-syn overexpressing animals were seen to exhibit less cell and terminal loss for an equivalent level of motor abnormalities. Prominent and persistent axonal pathology is only observed in the α-syn rat model. We suggest that, while neuronal and terminal loss mainly accounts for the behavioural impairment in the toxin-based model, similar motor deficits result from the combination of cell death and dysfunction of the remaining nigro-striatal neurons in the AAV-α-syn model. While the two models have been developed to mimic DA neuron deficiency, they differ in their temporal and neuropathological characteristics, and replicate different aspects of the pathophysiology of the human disease. This study suggests that the AAV-α-syn model replicates the human pathology more closely than either of the other two 6-OHDA lesion models.     

Effects of aging and β-amyloid on the properties of brain synaptic and mitochondrial membranes

Summary. The effects of aging and of different amyloid β-peptides (Aβ) on the properties of purified synaptosomal plasma and mitochondrial membranes were studied using different fluorescent dyes. Aging led to opposite membrane alterations in both mouse brain fractions. Cholesterol levels were significantly enhanced in synaptosomal plasma membranes (SPM) from aged mice only. Flexibility of membrane fatty acids was decreased in synaptosomal plasma and mitochondrial membranes, mobility of pyrene was enhanced, but in SPM only. With regard to acyl chain flexibility in aged brain membranes, both membrane preparations were less sensitive to Aβ. By contrast, effects of Aβ on the mobility of pyrene were not reduced for aged synaptic membranes, but even seemed to be enhanced in the case of aged mitochondrial membranes. The data presented significantly enhance our understanding of the mechanism of the Aβ's disordering effects on synaptosomal membranes that are also detectable for mitochondrial membranes and show for the first time that Aβ effects are modified by brain aging. This is of special interest since membrane alterations and in particular modifications of membrane cholesterol were recently linked to Alzheimer's Disease. Received October 6, 2000; accepted April 2, 2001     

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Title: It should reflect the scientific value of the study exactly and the language should be precise and peculiar. The concrete revise advices should be suggested if the title is not in accordance with the standards. c It should directly point out the ba…     

Out of sight out of mind? Support and information given to distant and near relatives of those with dementia

OBJECTIVES: Increasing attention has been paid to the needs of family members caring for a person with dementia but little has been written about the impact on the wider family. This paper was intended to see whether the need for information would stretch to those relatives living far from the patient. METHOD: A case-control study comparing two sets of relatives of community-dwelling probands in contact with secondary services and having a clinical diagnosis of dementia: one set of relatives living less than an hour away and another set living further away.The reported need for and source of information obtained by relatives was questioned using a specially designed questionnaire. Mini Mental State Examination (MMSE) and Clinical Dementia Ratings Scale were used with probands. RESULTS: Relatives living distantly from the person with dementia reported similar rates of subjective distress but were more often dissatisfied with information received. Distant relatives were also less likely to access information from books or lay societies. CONCLUSION: The impact of having a relative with dementia does not lessen with distance. The wider family need support and information as well as 'primary carers'. If the whole family is to be supported in their caring role, then clinicians and the lay societies need to widen their supportive net.     

Mechanisms of Neuroprotective Effects of Nicotine and Acetylcholinesterase Inhibitors: Role of α4 and α7 Receptors in Neuroprotection

Neurotoxicity induced by glutamate and other excitatory amino acids has been implicated in various neurodegenerative disorders including hypoxic ischemic events, trauma, and Alzheimer’s and Parkinson’s diseases. We examined the roles of nicotinic acetylcholine receptors (nAChRs) in survival of CNS neurons during excitotoxic events. Nicotine as well as other nicotinic receptor agonists protected cortical neurons against glutamate neurotoxicity via α4 and α7 nAChRs at least partly by inhibiting the process of apoptosis in near-pure neuronal cultures obtained from the cerebral cortex of fetal rats. Donepezil, galanatamine and tacrine, therapeutic acetylcholinesterase (AChE) inhibitors currently being used for treatment of Alzheimer’s disease also protected neuronal cells from glutamate neurotoxicity. Protective effects of nicotine and the AChE inhibitors were antagonized by nAChR antagonists. Moreover, nicotine and those AChE inhibitors induced up-regulation of nAChRs. Inhibitors for a non-receptor-type tyrosine kinase, Fyn, and janus-activated kinase 2, suppressed the neuroprotective effect of donepezil and galantamine. Furthermore, a phosphatidylinositol 3-kinase (PI3K) inhibitor also suppressed the neuroprotective effect of the AChE inhibitors. The phosphorylation of Akt, an effector of PI3K, and the expression level of Bcl-2, an anti-apoptotic protein, increased with donepezil and galantamine treatments. These results suggest that nicotine as well as AChE inhibitors, donepezil and galantamine, prevent glutamate neurotoxicity through α4 and α7 nAChRs and the PI3K-Akt pathway.     

Behavioral Profiles of Affected and Unaffected Siblings of Children with Autism: Contribution of Measures of Mother–Infant Interaction and Nonverbal Communication

We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months.     

Preschoolers’ Contribution to their Diagnosis of Depression and Anxiety: Uses and Limitations of Young Child Self-Report of Symptoms

Background The assessment of psychopathology in preschool aged children has traditionally relied exclusively on adult informants as children under 6 years-of-age have been widely regarded as developmentally unable to serve as valid reporters of their own mental state. Based on the finding of a valid preschool depressive syndrome, methods to obtain self-report of symptoms of depression and related anxiety directly from the child are now needed. Methods The Berkeley Puppet Interview (BPI), a novel measure of psychopathology designed for the young child informant, was administered to N = 110 preschool study subjects aged 4.0–5.6 who participated in a comprehensive assessment of preschool depression. Parents filled out the Child Behavioral Checklists (CBCL) and the diagnosis was derived using parent report on the Diagnostic Interview Schedule for children, version IV (DISC-IV-YC) at baseline and 6 months later. Results Findings suggest that young children may serve as useful reporters of several core and basic symptoms of depression and anxiety based on significant correlations with a variety of parent report measures administered concurrently and 6 months later. However, no significant correlations were found between preschool reports of more complex or abstract symptoms. Conclusion These findings taken together suggest that the young child can validly self-report on some key aspects of depression and anxiety and that self-report of young children should be sought in these domains. Findings also suggested that these self-reports are limited to the core and basic symptoms of these disorders and that direct age appropriate approaches may not be useful beyond that domain.     

Do Canada and the United States differ in prevalence of depression and utilization of services?

OBJECTIVE: This study compared the prevalence of depression and the determinants of mental health service use in Canada and the United States. METHODS: The study used data from preliminary analyses of the 2003 Joint Canada/United States Survey of Health, which measured Canadian (N=3,505) and United States (N=5,183) resident ratings of health and health care services. Cross-national comparisons were made for the 12-month prevalence of DSM-IV major depression, 12-month service use for mental health reasons according to the type of professional seen, and determinants of service use. RESULTS: The rates of depression were similar in Canada (8.2%) and the United States (8.7%). However, U.S. respondents without medical insurance were twice as likely as Canadian respondents and U.S. respondents with medical insurance to meet the criteria for depression. Rates of mental health service use did not differ between Canada (10.1%) and the United States (10.6%). In the United States, medical insurance was not a determinant factor of service use. However, U.S. respondents with no medical insurance were more likely than the other two groups to report an unmet need. Also, among those with depression, U.S. respondents with no medical insurance were less likely to use any type of mental health service (36.5%) than U.S. respondents with medical insurance (55.7%) and Canadians (55.7%). Further, a positive correlation between a mental health need and service use was observed in Canada but not for those without medical insurance in the United States. CONCLUSIONS: There was no difference in the prevalence of depression and mental health service use between Canada and the United States. Among those with depression, however, disparities in treatment seeking were found to be associated with medical insurance in the United States. Both Canada and the United States need to improve access to health services for those with mental disorders, and special attention is needed for those without medical insurance in the United States.     

Genetics of migraine and migraine accompagneé: a study of eighty-one children and their families

Eighty-one patients suffering from childhood onset migraine and their families were investigated for familial prevalences of epileptic seizures and migraine. The incidence of epileptic seizures was not increased above the epidemiological risk. - In all, migraine is largely inherited from maternal ascendents, irrespective of the sex of the index case. Clinical subtypes of migraine ("non-focal migraine" and migraine accompagnée) are not accompanied by respectively increased familial prevalences. - Onset of migraine is earlier in patients with a higher familial impact. These findings are discussed in context with a proposed multifactorial pathogenesis of migraine.     

Diagnosis and disclosure of dementia – A comparative qualitative study of Irish and Swedish General Practitioners

Objectives: To explore the attitudes of Irish and Swedish General Practitioners (GPs) to the diagnosis and disclosure of dementia to patients; to investigate GP under-graduate/post-graduate training in dementia; to examine the post-diagnostic support services available to GPs in both countries and to investigate the extent to which dementia is perceived as stigmatising.

Methods: A cross-national exploratory qualitative design was used. In-depth interviews were conducted with five Irish and four Swedish GPs. Interviews were transcribed, translated, thematically coded and categorised.

Results: Both Irish and Swedish GPs unequivocally considered the early diagnosis of dementia important but neither group was proactive in making a diagnosis. Both groups relied heavily on family members or patients to bring to their attention memory loss and cognitive impairment problems. Most GPs reported a reluctance to diagnose and several acknowledged going to considerable lengths to avoid using the word ‘dementia’. The Swedish GPs had more exposure to dementia-specific training, saw the value in training and were generally very satisfied with post-diagnostic dementia services available to patients, while Irish GPs were less likely to have undergone training, were more equivocal about its value and were very dissatisfied with the community services available.

Conclusion: Despite the presence of very adequate post-diagnostic support services for people recently diagnosed with dementia, the majority of Swedish GPs like their Irish counterparts displayed therapeutic nihilism and were reluctant to speak overtly to their patients about their dementia. Dementia continues to be a stigmatising illness for both Irish and Swedish GPs.     

Validity of auditory perceptual assessment of velopharyngeal function and dysfunction – the VPC-Sum and the VPC-Rate

ABSTRACT

Overall weighted or composite variables for perceptual auditory estimation of velopharyngeal closure or competence have been used in several studies for evaluation of velopharyngeal function during speech. The aim of the present study was to investigate the validity of a composite score (VPC-Sum) and of auditory perceptual ratings of velopharyngeal competence (VPC-Rate). Available VPC-Sum scores and judgments of associated variables (hypernasality, audible nasal air leakage, weak pressure consonants, and non-oral articulation) from 391 5-year olds with repaired cleft palate (the Scandcleft project) were used to investigate content validity, and 339 of these were compared with an overall judgment of velopharyngeal competence (VPC-Rate) on the same patients by the same listeners. Significant positive correlations were found between the VPC-Sum and each of the associated variables (Cronbachs alpha 0.55–0.87, P < 0.001), and a moderately significant positive correlation between VPC-Sum and VPC-Rate (Rho 0.698, P < 0.01). The latter classified cases well when VPC-Sum was dichotomized with 67% predicted velopharyngeal competence and 90% velopharyngeal incompetence. The validity of the VPC-Sum was good and the VPC-Rate a good predictor, suggesting possible use of both measures depending on the objective.     

Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase-3β and the microtubule-associated protein tau in the hippocampus and cerebellum of female rat

Gonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first- choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule-associated protein tau and glycogen synthase kinase-3β (GSK3β) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administration for 60 days. The animals were sacrificed, and tissue proteins were analyzed by Western blot. We observed that, in the hippocampus, administration of E2, P4, or TIB significantly decreased the protein content of hyperphosphorylated tau and increased the tau dephosphorylated form, whereas only treatment with TIB increased the content of the phosphorylated form of GSK3β. In the cerebellum, E2 and TIB treatments resulted in a significant decrease in the expression of hyperphosphorylated tau, whereas E2 and TIB increased phosphorylated GSK3β; P4 had no effect. These results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3β phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues.     

Quality of life and subjective well-being in schizophrenia and schizophrenia spectrum disorders: Valid predictors of symptomatic response and remission?

Abstract

Objectives. To examine quality of life and subjective well-being as predictors of symptomatic treatment outcome. Methods. Biweekly PANSS ratings were performed in 285 inpatients with schizophrenia spectrum disorders within a multicenter trial by the German Research Network on Schizophrenia. Quality of life and subjective well-being were assessed using the Medical Outcomes Study-Short Form 36-Item Health Survey (SF-36), the Subjective Well-being Under Neuroleptic Treatment Scale (SWN-K) and the Adjective Mood Scale (AMS). Response was defined as an initial 20% PANSS total score reduction and remission according to the consensus criteria. Correlation analysis, logistic regression and CART-analysis were performed. Results. In total, 81% of the sample achieved symptom response and 48% symptom remission. The statistical analyses revealed early improvement within the first two treatment weeks in the SWN-K scale to be a significant predictor for symptomatic response. Concerning symptomatic remission the SF-36 and SWN-K baseline scores as well as SWN-K early improvement showed significant predictive value. Conclusions. These results highlight the importance of the patient's self-perception and especially of early improvement of quality of life and subjective well-being for symptomatic treatment outcome.