Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Differential effects of bifrontal tDCS on arousal and sleep duration in insomnia patients and healthy controls

Background

Arousal and sleep represent basic domains of behavior, and alterations are of high clinical importance.

The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects

Rebound effects after withdrawal from hypnotics are believed to trigger their chronic use and to enhance the risk of tolerance and dependence. It was the purpose of this study to investigate the acute polysomnographic withdrawal effects after a 4 week treatment with standard doses of the non-benzodiazepine hypnotics zopiclone and zolpidem compared with triazolam and placebo. Healthy male subjects between 22 and 35 years of age participated in a parallel study design. They received either zopiclone 7.5 mg (n=11), zolpidem 10 mg (n=11), triazolam 0.25 mg (n=10) or placebo (n=7) over 4 weeks in randomized and double-blind order. Sleep EEG was registered during 2 nights before treatment under placebo, on days 1, 27 and 28 of treatment and on days 29, 30, 41 and 42 under placebo. Total sleep time and sleep efficiency were lower in the 1^st night after discontinuation of triazolam (p < 0.05, t-test). After withdrawal from zopiclone or zolpidem slight but not significant rebound effects concerning sleep continuity were observed. Self-rating scales showed minimal rebound insomnia after discontinuation of all three hypnotics. In the placebo group no changes of sleep parameters were observed. Assuming that rebound insomnia is part of a withdrawal reaction, this study indicates that the risks of tolerance and dependency are low when administering zopiclone or zolpidem at the recommended doses. Received: 13 September 2000 / Accepted: 7 May 2001     

Attention-deficit hyperactivity disorder as a potentially aggravating factor in borderline personality disorder

BACKGROUND: Clinical experience suggests that people with borderline personality disorder often meet criteria for attention-deficit hyperactivity disorder (ADHD). However, empirical data are sparse. AIMS: To establish the prevalence of childhood and adult ADHD in a group of women with borderline personality disorder and to investigate the psychopathology and childhood experiences of those with and without ADHD. METHOD: We assessed women seeking treatment for borderline personality disorder (n=118) for childhood and adult ADHD, co-occurring Axis I and Axis II disorders, severity of borderline symptomatology and traumatic childhood experiences. RESULTS: Childhood (41.5%) and adult (16.1%) ADHD prevalence was high. Childhood ADHD was associated with emotional abuse in childhood and greater severity of adult borderline symptoms. Adult ADHD was associated with greater risk for co-occurring Axis I and II disorders. CONCLUSIONS: Adults with severe borderline personality disorder frequently show a history of childhood ADHD symptomatology. Persisting ADHD correlates with frequency of co-occurring Axis I and II disorders. Severity of borderline symptomatology in adulthood is associated with emotional abuse in childhood. Further studies are needed to differentiate any potential causal relationship between ADHD and borderline personality disorder.     

Psychiatric comorbidity in patients with pharmacoresistant focal epilepsy and psychiatric outcome after epilepsy surgery

There are only a few studies in which both preoperative psychiatric comorbidity in pharmacoresistant focal epilepsy and its outcome after epilepsy surgery have been investigated. In this study, 144 patients evaluated for epilepsy surgery received psychiatric examination, 84 proceeding to intervention were reassessed postoperatively. Preoperatively, 60% met criteria for ICD-10- or epilepsy-specific psychiatric diagnosis. Twenty-seven percent, predominantly female, suffered from dysphoric disorder (DD) associated with temporal epileptogenic foci. Prevalence of DD correlated with complex partial seizure frequency and presence of ictal fear suggesting limbic-cortical dysregulation. Psychotic syndromes were linked to a history of febrile convulsions and left-sided temporomesial epileptogenic foci. High seizure frequency and early epilepsy onset predisposed to the development of personality disorders. Postoperative assessment revealed 18% of patients with "de novo" interictal affective disorders after surgery. Symptoms in 48% of patients with preoperative affective syndromes and 60% of patients with DD remitted after surgery. Seizure freedom and improved psychosocial status predicted remission of preoperative psychopathology.     

How smoking affects sleep: A polysomnographical analysis

ObjectiveSubjective quality of sleep is impaired in smokers compared with non-smokers, but there is only limited evidence from methodologically sound studies about differences in polysomnography (PSG) sleep characteristics. Therefore, this study used PSG to evaluate sleep in smokers and non-smokers while controlling for other parameters that affect sleep.MethodsAfter an adaptation night, PSG sleep laboratory data were obtained from 44 smokers (29 men and 15 women, median age 29.6 years) and compared with PSG data from 44 healthy, sex- and age-matched never smokers. Exclusion criteria were alcohol or other substance abuse, psychiatric or endocrine diseases, and treatment with any kind of psychotropic medication. Nicotine and cotinine plasma levels were measured (in the smoking group) and subjective sleep quality assessed in both groups.ResultsThe smokers had a Fagerström tolerance score of 6.4, consumed an average of 21.2 cigarettes per day and had been smoking for 13.1 years (median). Smokers had a shorter sleep period time, longer sleep latency, higher rapid eye movement sleep density, more sleep apneas and leg movements in sleep than non-smokers. There were no differences regarding parameters of spectral analysis of the sleep electroencephalogram as well as in the sleep efficiency measured by PSG. Nevertheless smokers rated their sleep efficiency lower on the Pittsburgh Sleep Quality Index compared with non-smoking individuals, but no differences were detected on the SF-A. Plasma cotinine level correlated negatively with slow wave sleep in the smoking group.ConclusionsSmokers showed a number of insomnia-like sleep impairments. The findings suggest that it is important for sleep researchers to control smoking status in their analyses. Further research should focus on the causes and consequences of impaired sleep during tobacco cessation, as sleep disturbances are a known risk factor for early relapse after initial tobacco abstinence.