Differential modulation of transendothelial electrical resistance by TRPV4 agonists is mediated by apoptosis and/or necrosis.

Transient receptor potential vanilloid 4 (TRPV4) has been implicated in many disease conditions also in the lung. Its activation leads to an increase endothelial permeability in an intracellular calcium-influx dependent manner. We investigated its function in vitro on primary human endothelial cells using two TRPV4 agonists, GSK1016790A and 4α-Phorbol 12,13-didecanoate (4α-PDD) and a selective TRPV4 blocker GSK2193874. Both TRPV4 agonists leaded to a reduction in transendothelial electrical resistance (TER) which was mediated however by differential cytotoxic effects. 4α-PDD induced apoptosis that could not be blocked by TRPV4 inhibition in HUVECs, whereas GSK1016790A selectively activated TRPV4 and reduced TER as a consequence of cellular necrosis. TRPV4 mediated cytotoxicity is poorly described and may provide significant context to the role of TRPV4 in barrier-function.

TRPV4 inhibition attenuates stretch-induced inflammatory cellular responses and lung barrier dysfunction during mechanical ventilation.

Mechanical ventilation is an important tool for supporting critically ill patients but may also exert pathological forces on lung cells leading to Ventilator-Induced Lung Injury (VILI). We hypothesised that inhibition of the force-sensitive transient receptor potential vanilloid (TRPV4) ion channel may attenuate the negative effects of mechanical ventilation. Mechanical stretch increased intracellular Ca2+ influx and induced release of pro-inflammatory cytokines in lung epithelial cells that was partially blocked by about 30% with the selective TRPV4 inhibitor GSK2193874, but nearly completely blocked with the pan-calcium channel blocker ruthenium red, suggesting the involvement of more than one calcium channel in the response to mechanical stress. Mechanical stretch also induced the release of pro-inflammatory cytokines from M1 macrophages, but in contrast this was entirely dependent upon TRPV4. In a murine ventilation model, TRPV4 inhibition attenuated both pulmonary barrier permeability increase and pro-inflammatory cytokines release due to high tidal volume ventilation. Taken together, these data suggest TRPV4 inhibitors may have utility as a prophylactic pharmacological treatment to improve the negative pathological stretch-response of lung cells during ventilation and potentially support patients receiving mechanical ventilation.

Fungal Planet description sheets: 214-280.

Novel species of microfungi described in the present study include the following from South Africa: Cercosporella dolichandrae from Dolichandra unguiscati, Seiridium podocarpi from Podocarpus latifolius, Pseudocercospora parapseudarthriae from Pseudarthria hookeri, Neodevriesia coryneliae from Corynelia uberata on leaves of Afrocarpus falcatus, Ramichloridium eucleae from Euclea undulata and Stachybotrys aloeticola from Aloe sp. (South Africa), as novel member of the Stachybotriaceae fam. nov. Several species were also described from Zambia, and these include Chaetomella zambiensis on unknown Fabaceae, Schizoparme pseudogranati from Terminalia stuhlmannii, Diaporthe isoberliniae from Isoberlinia angolensis, Peyronellaea combreti from Combretum mossambiciensis, Zasmidium rothmanniae and Phaeococcomyces rothmanniae from Rothmannia engleriana, Diaporthe vangueriae from Vangueria infausta and Diaporthe parapterocarpi from Pterocarpus brenanii. Novel species from the Netherlands include: Stagonospora trichophoricola, Keissleriella trichophoricola and Dinemasporium trichophoricola from Trichophorum cespitosum, Phaeosphaeria poae, Keissleriella poagena, Phaeosphaeria poagena, Parastagonospora poagena and Pyrenochaetopsis poae from Poa sp., Septoriella oudemansii from Phragmites australis and Dendryphion europaeum from Hedera helix (Germany) and Heracleum sphondylium (the Netherlands). Novel species from Australia include: Anungitea eucalyptorum from Eucalyptus leaf litter, Beltraniopsis neolitseae and Acrodontium neolitseae from Neolitsea australiensis, Beltraniella endiandrae from Endiandra introrsa, Phaeophleospora parsoniae from Parsonia straminea, Penicillifer martinii from Cynodon dactylon, Ochroconis macrozamiae from Macrozamia leaf litter, Triposporium cycadicola, Circinotrichum cycadis, Cladosporium cycadicola and Acrocalymma cycadis from Cycas spp. Furthermore, Vermiculariopsiella dichapetali is described from Dichapetalum rhodesicum (Botswana), Ophiognomonia acadiensis from Picea rubens (Canada), Setophoma vernoniae from Vernonia polyanthes and Penicillium restingae from soil (Brazil), Pseudolachnella guaviyunis from Myrcianthes pungens (Uruguay) and Pseudocercospora neriicola from Nerium oleander (Italy). Novelties from Spain include: Dendryphiella eucalyptorum from Eucalyptus globulus, Conioscypha minutispora from dead wood, Diplogelasinospora moalensis and Pseudoneurospora canariensis from soil and Inocybe lanatopurpurea from reforested woodland of Pinus spp. Novelties from France include: Kellermania triseptata from Agave angustifolia, Zetiasplozna acaciae from Acacia melanoxylon, Pyrenochaeta pinicola from Pinus sp. and Pseudonectria rusci from Ruscus aculeatus. New species from China include: Dematiocladium celtidicola from Celtis bungeana, Beltrania pseudorhombica, Chaetopsina beijingensis and Toxicocladosporium pini from Pinus spp. and Setophaeosphaeria badalingensis from Hemerocallis fulva. Novel genera of Ascomycetes include Alfaria from Cyperus esculentus (Spain), Rinaldiella from a contaminated human lesion (Georgia), Hyalocladosporiella from Tectona grandis (Brazil), Pseudoacremonium from Saccharum spontaneum and Melnikomyces from leaf litter (Vietnam), Annellosympodiella from Juniperus procera (Ethiopia), Neoceratosperma from Eucalyptus leaves (Thailand), Ramopenidiella from Cycas calcicola (Australia), Cephalotrichiella from air in the Netherlands, Neocamarosporium from Mesembryanthemum sp. and Acervuloseptoria from Ziziphus mucronata (South Africa) and Setophaeosphaeria from Hemerocallis fulva (China). Several novel combinations are also introduced, namely for Phaeosphaeria setosa as Setophaeosphaeria setosa, Phoma heteroderae as Peyronellaea heteroderae and Phyllosticta maydis as Peyronellaea maydis. Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

First Report of Albugo candida Causing White Rust on Lunaria annua in Italy.

Money plant or annual honesty (Lunaria annua L.) is an ornamental landscape plant used in flower beds and borders and also in flower arrangements. It is a biennial plant with large, pointed, oval leaves. Plants of L. annua showing white-to-cream, blister-like lesions on leaves and siliques (2) were found in private gardens where approximately 800 plants of 1,000 (approximately 80 to 90%) that were observed showed symptoms. The disease was also found in two ornamental nurseries, although it was limited to a few mother plants because of extensive fungicide treatments. The gardens and ornamental nurseries were located in Potenza Province (Basilicata Region, southern Italy). Sporangiophores were mostly straight or arched and almost cylindrical with attenuated base and flat or rounded apex and measured 29.2 to 33.4 × 12.8 to 13.4 µm. Sporangia, produced in chains and joined by short connectives, exhibited a spherical or angular shape, were subhyaline, contained vacuoles, and had average maximum and minimum diameters ranging from 15.8 to 18.8 and 14 to 16 µm, respectively. The morphological characteristics closely resembled those reported for Albugo candida (Pers.) Kuntze (3). Sori were collected from naturally and artificially inoculated tissues of L. annua, with the aid of a stereomicroscope, and used to extract genomic DNA via a DNeasy Plant Mini DNA extraction kit (Qiagen, Hilden, Germany) according to the manufacturer's directions. The extracted DNA was used as a template for amplification of the internal transcribed spacer (ITS) region of rDNA with primer pair ITS4/DC6 (1,4) and sequenced. One sequence, GenBank Accession No. GQ328846, matched several sequences of A. candida (Pers). Kuntze (e.g., GenBank Accession Nos. GQ328837, GQ328836, GQ328835, GQ328834, and AF271231), showing 98% identity. Pathogenicity tests were performed and repeated twice. Leaves of 10 healthy seedlings of L. annua were surface cleaned during several washings with distilled water and then spray inoculated with a suspension of 103 sporangia/ml of A. candida. Five healthy seedlings were spray inoculated with the same volume of sterile water and served as controls. Inoculated seedlings were maintained in a moist chamber for 48 h at 20°C before being moved to a shaded glasshouse at 16 to 24°C and 90% relative humidity. White rust symptoms, similar to those observed in natural conditions, appeared on leaves of inoculated seedlings 10 to 14 days later, demonstrating that A. candida was the causal agent of the disease. Control plants remained symptomless. White rust has been reported on L. annua in Europe (Czech Republic, Germany, Poland, and the United Kingdom) and in the northwestern United States (3). To our knowledge, this is the first report of A. candida infecting annual honesty plant in Italy. References: (1) P. Bonants et al. Eur. J. Plant Pathol. 103:345, 1997. (2) D. Choi et al. Mycotaxon 53:261, 1995. (3) D. A. Glawe et al. Online publication. doi:10.1094/PHP-2004-0317-01-HN. Plant Health Progress, 2004. (4) T. J. White et al. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: PCR Protocols. A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.

An overview on anticancer activities of the Viscum album extract Isorel.

The activity principle of the mistletoe (Viscum album L.) phytotherapeutics could be considered as combined cytotoxic and "biological response modifying" activities (increasing host defense against cancer) that result from the activities of the plant lectins and the other biologically relevant substances. We found before that the aqueous extract Isorel, produced by Novipharm GmbH (Pörtschach, Austria) from the entire plant (planta tota) of fresh mistletoe under standardized conditions with bioassay validated batch consistency, can be valuable in experimental adjuvant cancer therapy increasing efficiency of cyclophosphamide chemotherapy. In current study we found that Isorel increases the reactivity of the tumor-bearing mice lymphocytes to the mitogens (ConA and LPS) in vitro, thus indicating its immune stimulating effects for the cancer-immunosuppressed lymphocytes. Moreover, Isorel inhibited the incorporation of 3H-labelled amino acids (protein synthesis) in various malignant cell lines. For the growth inhibition mostly higher MW components were responsible, although even less than 500 Da components were also active. We further analyzed the effects of drug application in vicinity of tumor (murine mammary carcinoma) and compared it with systemic effects. The animals carried mammary carcinoma in both hind limbs and were also injected with tumor cells i.v. to develop artificial lung metastases. Isorel was applied only at the right side (in the limb distal from the tumor) and caused persistent and almost complete inhibition of the tumor growth for 2/7 animals. Anticancer effects were less pronounced on the contralateral side tumors, although tumor growth rate was transiently reduced for some mice. Histology revealed that Isorel treatment, both at the side of tumor and systemically, increased the incidence of apoptosis and necrosis in the tumors, while reduction of mitosis was noticed only for the tumors in vicinity of the tumor exposed to Isorel. Finally, animals treated with Isorel had, on the average, three times less lung metastases than the controls. Thus, we conclude that both local and systemic effects of the application of Isorel could be of benefit for the tumor-bearing organism resulting in immunomodulation combined with tumor growth inhibition and reduction of metastases. According to the in vitro results, antitumorous effects could be the result not only of the mistletoe lectins and the other high MW factors, but also of the very low MW (< 500 Da) substances that deserve further analyses.

Polymer supported chromium porphyrin as catalyst for polycarbonate formation in supercritical carbon dioxide.

A new polymer-supported chromium porphyrin has been prepared and fully characterised; its catalytic activity and recyclability were investigated for the ring-opening copolymerisation of 1,2-cyclohexene oxide (CHO) and carbon dioxide (CO2).

Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10.

Numerous findings indicate that specific plant lectins acting against cancer could be major active components of Viscum album extracts, although activity of low molecular weight components (peptides, carbohydrates and alkaloids) might be as essential for the beneficial activity of the plain plant extracts, too. Thus, active principle of Viscum album extracts is still not understood, and is difficult to be analysed because of the complex composition of the extracts and uncertainty of the standardised effectiveness (batch consistency) of the extracts. The aims of this study were to compare the concentration dependent effects of the pure mistletoe lectin (ML-1) with the fresh plant Viscum album extract (Isorel) and its different MW components on the in vitro growth of ConA stimulated lymphocytes, on the growth and tumorigenicity (artificial lung metastases development) of murine melanoma B16F10 cells, and to compare concentration dependent effects of the different types of the Viscum album extracts in vitro (applying novel type of MTT assay). The results obtained indicate that the effects of Isorel used at high dose could be result of toxic activity of the mistletoe lectins ("ML-1 like" activity). Unlike ML-1, if used at low concentrations, Isorel selectively inhibited tumor cells, due the activity of the low MW components. On the other hand, the number of tumor nodules was reduced (in comparison to the control) equally in the lungs of mice injected with B16F10 cells pre-treated in vitro with the plain Viscum album extract or any of its modifications or ML-1. Hence, it is supposed that the beneficial therapeutic effects of Isorel might result from the combined biological activity of the high and the low MW components not lectins only. Similarly, in MTT assay low concentrations of all types of the Viscum album extract showed stronger inhibiting activity for B16F10 and HeLa cells than pure ML-1. According to these results we propose a standardisation of aqueous Viscum album extracts by comparing their and ML-1 concentration dependent activity on the tumor cells in vitro applying MTT bioassay described which should be relevant for further evaluation of their active principle and for improvement of biotherapy of cancer.

[Are pectoral implanted cardioverter defibrillators subject to electromagnetic interference by D-net mobile-phones]. / Beeinflussen D-Netz Mobiltelefone pektoral implantierte Defibrillatoren?

The use of GSM or D-net mobile-phones has been proven to disturb antibradycardiac pacemaker function by electromagnetic fields. Therefore interference between these phones and subpectroral ICD-systems is conceivable. We investigated effects on programmed parameters, sensing and pacing, as well as detection and termination of arrhythmias in 15 patients with pectoral single-lead ICD-systems (Cardiac Pacemaker Inc., Ventak PRX III and Ventak Mini). During all tests, including stand-by mode, incoming and outgoing calls and transmission, no malfunction of the ICDs occurred. In conclusion, the use of a D-net mobile phone (European GSM-standard) by patients with subpectoral ICD-systems of the tested types seems to be safe.

[Psychosomatic and somatopsychic aspects of myasthenia gravis. A critical review of the literature]. / Psychosomatische und somatopsychische Aspekte der Myasthenia gravis. Ein kritischer Literaturüberblick.

In an extensive literary abstract the up to now existing scientific research strategies and results concerning the psychosomatics of myasthenia gravis are introduced. While the pioneers of myasthenia-research already registered psychological disorders that were separated from differential diagnostic conversion neurosis, new studies show the noticeable high prevalence of psychopathological symptoms in myasthenia-patients. Besides monistic-somatic models, psychosomatic attempts of explanation were put forth in the past. Authors seem to agree at least with regard to psychological factors being able to influence symptom manifestation and course on a casuistic basis. Somatopsychic interdependencies seem to be of more significance, as it is stressed by coping-research. However controlled longitudinal studies lack yet, so far as to what degree psychosocial and somatic factors are clinically relevant with regard to coping with the disease. Perspectives for future research are given finally.