Phase-dependent expression of matrix metalloproteinases and their inhibitors in demyelinating canine distemper encephalitis

Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent enzymes that cleave molecules of the extracellular matrix, and thus are able to open the blood-brain-barrier and affect myelin. Their inhibitors (TIMPs) are important candidates for the therapy of demyelinating diseases. To establish an immunohistochemical profile of MMP and TIMP expression in plaque variants in dogs with spontaneous demyelinating distemper encephalitis, paraffin-embedded cerebella were studied employing the avidin-biotin-peroxidase complex method with a panel of nine polyclonal (anti-MMP-1, -3, -7, -9, -12, -13, -14, -TIMP-1, and -2) and two monoclonal antibodies (anti-latent MMP-2, and -MMP-11). All MMPs and TIMPs were prominently up-regulated in acute and subacute non-inflammatory lesions, and double-labeling techniques showed that they were mainly expressed by astrocytes and brain macrophages/microglia. In subacute inflammatory and chronic plaques, a moderate to strong decrease of MMP and TIMP expression compared to acute lesions was observed. In these phases MMP-11, -12, and -13 were still moderately present. In addition to astro- and microglia, invading perivascular mononuclear cells were positive for MMPs and TIMPs. In summary, there seems to be a phase-dependent expression of MMPs and TIMPs in demyelinating canine distemper encephalitis, and an MMP-TIMP imbalance might account for the lesion progression in this disease.     

Human ependymomas reveal frequent deletions on chromosomes 6 and 9

Ependymomas are glial tumors of the brain and spinal cord. Genetic aberrations associated with the development of these tumors have not been fully identified yet. In previous cytogenetic and comparative genomic hybridization studies, multiple genomic imbalances in ependymomas were found, including partial or whole chromosome losses (1p, 4q, 6q, 9, 10, 11, 13, 16, 17, 19q, 20q and 22q). The aim of this study was to map particularly the commonly affected regions in ependymomas. Thirty-three pairs of matched normal and tumor specimens from ependymoma patients were genotyped using 34 polymorphic microsatellite markers distributed over 15 chromosomes. Loss of heterozygosity (LOH) was found in 26 of 33 tumors (78.8%). The most frequent LOHs were found on the long arms of chromosomes 6 (30.3%) and 9 (27.3%). LOH was also detected on 3p14 (13.3%), 10q23 (10.3%) and 11q (18.2%). Because of the high percentage of LOH on chromosome 6 and 9, we conclude that important tumor suppressor genes are situated on these two chromosomes.Dedicated to Prof. Dr. H.K. Mueller-Hermelink's 60th birthday.     

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.     

Bioelectrical behaviour of hypoxic human neocortical tissue under the influence of nimodipine and dimethyl sulfoxide

Nimodipine and dimethyl sulfoxide (DMSO) have been shown to affect electrophysiological responses in rodent brain tissue in an vitro model of hypoxia. In the present study, the same agents were now examined for their effects on human neocortical brain slices under repeated hypoxic conditions. DMSO (0.4%), with and without addition of nimodipine (40 micromol/l), did not increase the latency of anoxic depolarization (AD). This finding is not in line with our previous observations of DMSO effects, with and without nimodipine, on brain slices of guinea pigs. AD latency was significantly longer in human neocortical brain slices compared with hippocampal slices of rodents even without any pharmacological influence. A possible acute effect of DMSO-nimodipine may therefore be masked by an interspecies difference of hypoxia resistance.     

Effects of valproic acid,carbamazepine, and phenobarbitone on the fatty acid composition of erythrocyte membranes in children

PURPOSE: To investigate a possible relation between antiepileptic drugs (AEDs) and the fatty acid composition of membranes. METHODS: Fatty acid (FA) composition of erythrocytes was studied in children with epilepsy receiving AED monotherapy. Children taking valproate (VPA, n = 28), carbamazepine (CBZ, n = 17), or phenobarbitone (PB, n = 14) were compared with healthy controls (n = 25). FAs were measured by capillary-gas chromatography (GC-FID). RESULTS: Significant changes (p < 0.05) in the FA composition of membranes were found. In children treated with VPA, C13:0 was decreased (8.2 +/- 2% vs. 10.7 +/- 4% in controls) and C14:0 increased (1.4 +/- 0.5% vs.1 +/- 0.5% in controls). C17:0 again was reduced (9.9 +/- 4% vs. 13.2 +/- 6% in controls), whereas the long-chained acids were enhanced: C18:2n-6 (6 +/- 2.4% vs. 3.9 +/- 2.5% in controls), and C20:4n-6 (1.9 +/- 1.7% vs. 1.4 +/- 0.5% in controls). The nonidentified FAs also increased with VPA therapy: 2.5 +/- 0.8% versus 1.7 +/- 0.9% in controls. Children treated with CBZ showed only minimal changes of FA composition: C13:0 was decreased compared with controls (8 +/- 2% vs. 10.7 +/- 4%). No changes were seen in patients taking PB. The mean corpuscular volume (MCV) showed important differences between the study groups: MCV was 84.7 +/- 6.0 fl during VPA therapy (p < 0.001) and 85.7 +/- 4.1 fl with CBZ (p < 0.001). During PB, the MCV increased to 82.87 +/- 3.29 fl compared with controls (78.73 +/- 4.92 fl; p < 0.01). CONCLUSIONS: VPA therapy is associated with changes of the FA composition of membranes, which is not the case with PB therapy. The implications of this finding remain to be established.     

Diffuse perineuronal nets and modified pyramidal cells immunoreactive for glutamate and the GABA(A) receptor alpha1 subunit form a unique entity in rat cerebral cortex

Perineuronal nets (PNs) consisting of polyanionic chondroitin sulfate proteoglycans (CSPG) and other extracellular matrix components create an exceptional microenvironment around certain types of neurons. In rat neocortex, three types of PNs can be distinguished after staining with Wisteria floribunda agglutinin (WFA) by their different morphological structure: lattice-like PNs associated with subpopulations of nonpyramidal neurons, weakly labeled PNs showing a pyramidal morphology, and diffuse PNs that possess a thick, strongly labeled matrix sheath located mainly in layer VIb above the white matter. The type of neuron surrounded by diffuse nets has not been described so far. This study is focused on the cytochemical and morphological characteristics of neurons associated with diffusely contoured PNs in rat parietal cortex using immunocytochemical staining, intracellular injection, and retrograde tracing methods. Cells surrounded by diffuse PNs were glutamate-immunoreactive in contrast to nonpyramidal, net-associated neurons that showed immunoreactivity for GABA, the calcium-binding protein parvalbumin and the potassium channel subunit Kv3.1b. Both groups of PN-ensheathed cells were mostly immunoreactive for the GABA(A) receptor alpha1 subunit. Lucifer Yellow-injected neurons surrounded by diffuse PNs displayed the morphological properties of modified pyramidal cells with intracortical main axons. Many neurons with diffuse PNs were retrogradely labeled over a long distance after Fluoro-Gold tracer injection in the parietal cortex, but remained unlabeled after intrathalamic injection. We conclude that neurons associated with diffuse PNs are a subpopulation of glutamatergic modified pyramidal cells that could act as excitatory long-range intracortically projecting neurons.     

Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases

Destruction of myelin and oligodendrocytes leading to the formation of large demyelinated plaques is the hallmark of multiple sclerosis (MS) pathology. In a subset of MS patients termed pattern III, actively demyelinating lesions show preferential loss of myelin-associated glycoprotein (MAG) and apoptotic-like oligodendrocyte destruction, whereas other myelin proteins remain well preserved. MAG is located in the most distal periaxonal oligodendrocyte processes and primary "dying back" oligodendrogliopathy may be the initial step of myelin degeneration in pattern III lesions. In the present study, various human white matter pathologies, including acute and chronic white matter stroke, virus encephalitis, metabolic encephalopathy, and MS were studied. In addition to a subset of MS cases, a similar pattern of demyelination was found in some cases of virus encephalitis as well as in all lesions of acute white matter stroke. Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-1alpha in various cell types, including oligodendrocytes. Our data suggest that a hypoxia-like tissue injury may play a pathogenetic role in a subset of inflammatory demyelinating brain lesions.     

Detecting panic disorder in medical and psychosomatic outpatients: comparative validation of the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire, a screening question, and physicians' diagnosis

OBJECTIVES: To compare the validity of detecting panic disorder using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), a screening question, and physicians' diagnosis, and to test whether modified evaluation algorithms improve the operating characteristics of these questionnaires. Additionally, patient and physician acceptability of the screening questionnaires was investigated. METHODS: The total sample of 499 patients comprised 348 medical outpatients and 151 psychosomatic outpatients. The Structured Clinical Interview for DSM-IV (SCID) was the criterion standard for the presence of a panic disorder. Sensitivity, specificity, predictive values, and overall accuracy were compared for the different measures. The conditional test characteristics were calculated based on the observed prevalence of panic disorder in the medical and psychosomatic subsample, respectively. RESULTS: Panic disorder was diagnosed in 4.3% of the medical outpatients and in 19.2% of the psychosomatic outpatients. The HADS, PHQ, and screening question achieved good operating characteristics. In contrast, physicians detected only 15% of cases with panic disorder. Modified evaluation algorithms of the questionnaires lead to an improvement of test characteristics. Of all measures, the PHQ had the best operating characteristics. The use of screening questionnaires was accepted by 96% of the patients and 97% of the physicians. CONCLUSIONS: The questionnaires as well as the screening question performed well in detecting panic disorder. Thus, the integration of these highly accepted measures into clinical evaluation is suggested. Recommendations for the selection of specific evaluation algorithms are given.     

Disturbed sleep in children with Tourette syndrome: a polysomnographic study

OBJECTIVE: To evaluate objective data on sleep quantity/quality and motor activity during night sleep in children with Tourette syndrome (TS). METHOD: Polysomnography of 17 unmedicated TS children (ages: 7;11-15;5, mean: 11;10 years) without comorbid attention-deficit hyperactivity disorder (ADHD) was compared with 16 age-, sex- and IQ-matched healthy controls. Sleep analyses according to the procedure of Rechtschaffen and Kales were supplemented by counting epochs with short arousal-related movements (相似文献   

Analytic child and adolescent psychotherapy in school refusal

School refusal can be divided into different subgroups, i.e. truancy and school-related fears and Phobias. Psychodynamic psychotherapy is primarily indicated in the treatment of school phobia, which is caused by relationship-based separation anxiety due to fixed dyadic patterns. To avoid further chronification a triangular treatment process should be started. If the child is missing out on school, an in-patient treatment should be considered. Thereby, dysfunctional phantasies can be replaced by age-appropriate ego-functions. With parents projective and identification-processes and libidinous overrepresentations can be worked through. School related fears are not psychoneurotic disorders, but real fears regarding violence or unattainable academic demands. Other forms of therapy and educational interventions are indicated in these cases. Parents can be counselled psychodynamically, if needed. Truancy should be treated by educational means, including interventions by social services if indicated.