Respiratory syncytial virus infection influences tight junction integrity.

Respiratory syncytial virus (RSV) is an important risk factor of asthma development and is responsible for severe respiratory tract infections. However, the influence of RSV infection on barrier function of bronchial epithelial cells in vitro and in vivo is still unclear. The aim of this study was to analyse the role of RSV in tight junction (TJ) regulation and to compare epithelial integrity between asthmatic and healthy individuals upon RSV infection. Healthy and asthmatic human bronchial epithelial cells (HBECs) were differentiated at air-liquid interface (ALI) and infected with RSV and ultraviolet (UV)-irradiated RSV. TJ expression and their integrity were analysed by quantitative polymerase chain reaction (qPCR), transepithelial resistance (TER) and paracellular flux. To determine the effect in vivo, BALB/c mice were infected intranasally with RSV or UV-irradiated RSV A2. Bronchoalveolar lavage and TJ integrity were analysed on days 1, 2, 4 and 6 post-infection by qPCR, bioplex and confocal microscopy. RSV increased barrier integrity in ALI cultures of HBEC from healthy subjects, but no effect was found in HBECs from asthmatics. This was not associated with an increase in TJ mRNA expression. In vivo, RSV induced lung inflammation in mice and down-regulated claudin-1 and occludin mRNA expression in whole lungs. Surprisingly, RSV infection was not observed in bronchial epithelial cells, but was found in the lung parenchyma. Decreased expression of occludin upon RSV infection was visible in mouse bronchial epithelial cells in confocal microscopy. However, there was no regulation of claudin-1 and claudin-7 at protein level.

Histamine receptor 2 modifies iNKT cell activity within the inflamed lung.

BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.

[Psychoactive mushrooms - an update]. / Uber den Gebrauch psychoaktiver Pilze als Rauschmittel.

Psychoactive mushrooms ("magic mushrooms") have been consumed in northern Europe since the late seventies. Recently, the use of hallucinogenic fungi has become popular among young people again. In autumn, psychoactive mushrooms can be collected from their natural habitats throughout Europe. Some species are cultivated in the Netherlands and are sold in "smart-shops" or via Internet. In Germany, dried specimens are sold as "Duftkissen" (aroma pads). The article reviews the common psychoactive species and illustrates medical risks.

[Pharmacotherapeutical approaches to insomnia patients with cardiac diseases and after heart transplantation]. / Pharmakotherapeutische Behandlungsstrategien der Insomnie bei Patienten mit kardialen Erkrankungen und nach Herztransplantation.

Insomnia in patients with heart transplantation and cardiac disease is a common problem. Organic factors, immunodepressant medication (e.g. ciclosporine and steroids) and psychological factors may account for this symptom. The article reviews different hypnotic drugs and their value in the treatment of insomnia. For short-time treatment, medication with benzodiazepine hypnotics may be useful. If the problems of drug dependence and rebound insomnia are taken into consideration, treatment with non-benzodiazepine hypnotics offers more safety and comfort. If insomnia is part of a depressive syndrome, pharmacotherapeutical intervention with antidepressive sedative medication is required. With regard to cardiac disease, treatment with mirtazapine, nefazodone or trazodone should be preferred because of the chinidine-like effect of tricyclic antidepressants (TCA). Sedative neuroleptic medication (e.g. melperone) is commonly given to geriatric patients; nevertheless, patients with chronic insomnia may also benefit from this medication. The risks and benefits of hypnotic drugs are discussed especially in relation to pharmacological interaction (cytochrome system) and cardiac disease.

[Toxic psychoses from atropine and scopolamine]. / Intoxikationspsychosen durch Atropin und Skopolamin.

Psychoses caused by an intoxication with atropine or scopolamine are rarely published. Nevertheless atropine and scopolamine were being used in the ancient civilisations and are still in use today. The intoxication is characterised by dose-dependent and substance-dependent syndrome with specific central and peripheral symptoms. Atropine and scopolamine cause a central and peripheral anticholinergic blockade of the muscarine receptor. Psychiatric symptoms include restlessness, excitement, hallucinations, euphoria, disorientation but also stupor, coma and respiratory depression. History, pathophysiology and clinical symptoms of the intoxication due to the alkaloids of the solanaceae are presented. A review of literature is given and four own cases observed in one year are introduced.

Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA.

In several vertebrate species, Borna disease virus (BDV), the prototype of a new group of animal viruses, causes central nervous system disease accompanied by diverse behavioral abnormalities. Seroepidemiological data indicate that BDV may contribute to the pathophysiology of certain human mental disorders. This hypothesis is further supported by the detection of both BDV antigens and BDV RNA in peripheral blood mononuclear cells (PBMCs) of patients with psychiatric disorders and the isolation of BDV from such PBMCs. Here we describe serological and molecular epidemiological studies on psychiatric patients and healthy individuals from the area of Homburg, Germany. Using a novel Western blot (immunoblot) assay, we found a BDV seroprevalence of 9.6% among 416 neuropsychiatric patients, which is significantly higher than the 1.4% found among 203 healthy control individuals. Human sera displayed a prominent immunoreactivity against the virus nucleoprotein, the p40 antigen. Reverse transcriptase-mediated PCR analysis of RNA extracted from PBMCs of a subset of 26 of the neuropsychiatric patients revealed that 50% were BDV RNA positive. Three of the 13 BDV RNA-positive patients also had BDV-positive serology, whereas one patient with serum antibodies to BDV p40 antigen did not harbor detectable BDV RNA in PBMCs. BDV p40 and p24 sequences derived from human PBMCs exhibited both a high degree of inter- and intrapatient conservation and a close genetic relationship to animal-derived BDV sequences.

[Delinquency under drug influence (author's transl)]. / Straftaten unter Einfluss von Drogen.

In delinquency, connected with alcohol, the immediate and acute effect of the substance is prominent, whereas in delinquency connected with drugs, one has to deal with chronic effects. The criteria for judging drunken offenders also stand as a model for judging the responsibility of the addicted offender for his crime. We consider: 1. the personality of the offender 2. the way, the amount and the point of time of the last intake of the drug 3. the potential dependence 4. the psychopathological state at the time of offense and at the time of examination 5. the kind of the offense itself. Most cases, which have to be examined, deal with indictable offenses, which were undertaken, in order to get new supply, i.e. "supply-offenes". These cases surmise, that the offender is physically addicted, that he knows about withdrawal symptoms from own experience, and that he committed the crime purely for securing his personal supply. We differentiate between direct "supply-offenses" (i.e. direct stealing by the addict himself) and indirect "supply-offenses" (i.e. mainly trading and commission business). For the latter offenses the state of consciousness and insight at the time of offense does not serve as a suitable criterion for judging the responsibility for the crime, since these offenders usually are not deprived of their drugs and therefore in a stable state of mind. Therefore the inner situation and the motivation for carrying out the crime has to be analysed carefully. For these indirect "supply-offenses" reduced responsibility for the offense has to be considered, whereas for direct "supply-offenses" a total lack of responsibility can be assumed.

[Problems of toxic psychosis as illustrated on the example of the so-called LSD psychosis]. / Zur Frage der toxischen Psychose am Beispiel der sog. LSD-Psychose

The effects of LSD are characterized by a number of disturbances of perception and experience, which can be observed in the fields of visual, spatial and temporal perception and of affectivity. We also see disturbances of experience, which can otherwise be observed only in psychoses, for example reduction or change of cognitive functions, but also depersonalization and euphoria. In atypical courses of intoxication ("horror-trips") anxiety and excitement are predominant. Atypical courses of intoxication may be interrupted by "talk down" and additional application of tranquilizers. In a certain number of LSD-users in our clinic we saw psychoses. We classify them into flash-backs, exogenic (toxic) psychoses and so-called "endoform psychoses". The latter implies three possible constellations: accidental coincidence of LSD-use and psychosis; pre-existing psychosis with symptomatic use of LSD as an attempt of self-treatment; finally the onset of a psychosis may be triggered by the use of the halluzinogen. From the symptomatological cross-section they cannot reliably be distinguished from real schizophrenia. An independent nosological unit "LSD-psychosis" does not seem to exist.