Factors affecting the toxicity of rotting carcasses containing Clostridium botulinum type E

Mice killed shortly after receiving c. 2000 spores of a type E strain of Clostridium botulinum per os were incubated at one of five chosen temperatures together with bottles of cooked meat medium seeded with a similar inoculum. After incubation the rotting carcasses were homogenized. Sterile membrane filtrates of the homogenates (10%, w/v) and pure cultures were then titrated for toxicity. Some of the main findings were confirmed with two further type E strains. Toxicity produced at 37 degrees C was poor in both carcasses and cultures (200-20,000 mouse intraperitoneal LD/g or ml). It was good in both systems at 30 and 23 degrees C, usually reaching 20,000-200,000 LD/g or ml, and in carcasses occasionally more; at 30 degrees C maximal toxicity was reached more quickly in carcasses than in cultures. Prolonged incubation (36-118 days) at 30 or 23 degrees C resulted in complete loss of toxicity in virtually all carcasses but not in cultures. At 16 degrees C the development of toxicity in carcasses was strikingly greater than in cultures. At 9 degrees C neither system produced more than slight toxicity after prolonged incubation. Trypsinization increased the toxicity of cultures but not usually of carcasses. Unfiltered carcass homogenate (10%, w/v) with maximal intraperitoneal toxicity was harmless for mice by mouth in doses of 0.25 ml. These findings differed in important respects from those made earlier with a type C strain.     

Kardiale Manifestationen der HIV-Infektion

Zusammenfassung. Die Infektion mit dem humanen Immundefizienzvirus (HIV) betrifft nicht nur das Immunsystem des menschlichen Organismus, sondern schließt vielmehr eine Reihe weiterer Organsysteme mit ein. Es wird angenommen, dass bei 5-15% der HIV-positiven Patienten kardiale Manifestationen auftreten. Zu den häufigsten HIV-assoziierten kardialen Manifestationen gehören der Perikarderguss und die chronisch aktive, fokale oder diffuse Myokarditis. Endokardiale Manifestationen bei HIV-positiven Patienten treten in Form der infektiösen Endokarditis und der nichtbakteriellen thrombotischen Endokarditis auf. In der Regel weisen HIV-assoziierte kardiale Manifestationen einen langsam progredienten Krankheitsverlauf auf. Komplikationen sind Folge eines langfristig unentdeckten Fortschreitens der Erkrankung, aber auch schnell progredienter Verlaufsformen. Aufgrund der Vielzahl HIV-assoziierter kardialer Manifestationen und deren möglicher Komplikationen ist daher neben der Früherkennung ein effektives diagnostisches und therapeutisches Vorgehen erforderlich. Seit Einführung der Proteaseinhibitoren in den 90er Jahren und der Anwendung der hochaktiven antiretroviralen Kombinationstherapie (HAART) konnten sowohl Mortalität als auch Morbidität der HIV-Infektion deutlich gesenkt werden. Die Auswirkungen der HAART auf das kardiovaskuläre System sind bisher nur in Ansätzen bekannt. Als Nebenwirkungen wurden metabolische Veränderungen in Form von Hyperlipoproteinämie und Insulinresistenz bei einer Vielzahl HIV-positiver Patienten beobachtet. Es kann davon ausgegangen werden, dass durch den Anstieg der kardiovaskulären Risikofaktoren unter der HAART in den nächsten Jahren eine erhöhte Rate kardialer Erkrankungen bei HIV-positiven Patienten auftreten wird. In dem vorliegenden Übersichtsartikel wird ein Überblick über die häufigsten kardialen Erkrankungen bei HIV-Infektionen gegeben. Zusätzlich werden Vorschläge zu Diagnostik und Therapie unterbreitet und eine Einschätzung über Veränderungen der HIV-assoziierten kardialen Manifestationen nach Einführung der HAART vorgenommen. Abstract. The human immunodeficiency virus (HIV) does not only affect the immune system. Other organs including the cardiovascular system are influenced by the HIV as well. Most common HIV-associated cardiac manifestations are pericardial effusion and chronic active, focal or diffuse myocarditis. In addition to peri- and myocardial disease, endocardiac manifestations occur as infective endocarditis and nonbacterial thrombotic endocarditis in HIV-infected patients. Although most of the cardiac manifestations associated with HIV-infection exhibit a slow progression, rapid courses may lead to fatal complications. Early screening of HIV-infected patients will identify the potentially fatal complications of HIV disease and permit efficient treatment. The use of highly active antiretroviral therapy (HAART) significantly reduced the mortality and morbidity of HIV-infected patients. However, the impact that HAART will have on the incidence and prevalence of cardiac complications in HIV-infected patients is still unknown. It can be predicted, that the long-term viral infection and the increase of cardiovascular risk factors by HAART will probably lead to an increased prevalence of HIV-infected individuals with cardiac complications in the next decade. The present review describes the most frequent HIV-associated cardiac manifestations including diagnostic and therapeutic perspectives.     

Dioxinlike components in incinerator fly ash: a comparison between chemical analysis data and results from a cell culture bioassay.

Potent polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxinlike polychlorinated biphenyls (PCBs) are among the most relevant toxic emissions from incinerators. Induction of cytochrome P450 1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity in mammalian cell culture (EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxinlike compounds. Fly ash extracts from municipal waste incinerators (MWI), a crematorium, wood combustors, and a noble metal recycling facility were analyzed in the EROD bioassay using rat hepatocytes in primary culture. Fractions containing 2,3,7,8-substituted PCDDs/PCDFs, dioxinlike PCBs, and 16 major polycyclic aromatic hydrocarbons (PAHs) were isolated from the extract and analyzed by gas chromatography-mass spectrometry (GC-MS) and by the EROD bioassay. It was found that with MWI samples the bioassay of the extract resulted in a two- to fivefold higher estimate of TCDD equivalents (TEQ) than the chemical analysis of PCDDs/PCDFs and PCBs. However, the outcome of both methods was significantly correlated, making the bioassay useful as a rough estimate for the sum of potent PCDDs/PCDFs and dioxinlike PCBs in extracts from MWI fly ash samples and in a fly ash sample from a crematorium. In noble metal recycling facility and wood combustor samples, higher amounts of PAHs were found, contributing to more pronounced differences between the results of both methods. The remaining unexplained inducing potency in fly ash samples probably results from additional dioxinlike components including certain PAHs not analyzed in this study.The hypothesis that emissions from MWI of hitherto unidentified dioxinlike compounds are higher by orders of magnitude than emissions of potent PCDDs/PCDFs and dioxinlike PCBs could not be confirmed. We found no indication for a marked synergistic interaction of dioxinlike fly ash components in the bioassay.     

Identification of cytotoxic principles from Fusarium avenaceum using bioassay-guided fractionation

The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue™ assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum.     

The interaction of endothelin receptor responses in the isolated perfused rat lung

To gain more insight into the complex pulmonary interactions of endothelins (ET), we studied airway and vascular responses to endothelins in isolated perfused rat lungs in the presence of the novel ET_B-receptor antagonist BQ788. In particular we focused on airway responses and on prostacyclin release. The effectiveness of BQ788 in our system was shown by its ability to concentration-dependently prevent vasoconstriction (IC₅₀ 0.1μM), bronchoconstriction (IC₅₀ 0.1μM) and prostacyclin production (IC₅₀<0.1μM) induced by the ET_B-receptor agonist IRL1620 (1nmol). Airway responses to ET-1: ET-1-induced bronchoconstriction was aggravated by BQ123 (1 or 8μM), while BQ788 pretreatment (1 or 8μM) showed no significant effect. Simultaneous treatment with 8μM BQ123 and BQ788 attenuated the ET-1-induced bronchoconstriction. Vascular responses to ET-1: ET-1 (1nmol)-induced vasoconstriction was potentiated by BQ788 (1 or 8μM), but attenuated by the ET_A-receptor antagonist BQ123 (1μM). In the presence of BQ788 diminished amounts of the stable prostacyclin metabolite 6-keto-PGF_1α were detected in the perfusate. Simultaneous treatment with 8μM BQ123 and BQ788 completely prevented the ET-1-induced vasoconstriction. Conclusions: Both ET_A- and ET_B-receptors contribute to ET-1-induced vasoconstriction and bronchoconstriction. The ET-1-induced vasoconstriction is attenuated by stimulation of ET_B-receptors, a response that is partly mediated by prostacyclin. Due to the mutual interactions between ET_A- and ET_B-receptors, simultaneous inhibition of both receptors is required to prevent the deleterious effects of ET-1 on lung functions. Received: 17 October 1996 / Accepted: 16 May 1997     

Independent component analysis and clustering improve signal-to-noise ratio for statistical analysis of event-related potentials

OBJECTIVE: To evaluate the effectiveness of a new method of using Independent Component Analysis (ICA) and k-means clustering to increase the signal-to-noise ratio of Event-Related Potential (ERP) measurements while permitting standard statistical comparisons to be made despite the inter-subject variations characteristic of ICA. METHODS: Per-subject ICA results were used to create a channel pool, with unequal weights, that could be applied consistently across subjects. Signals derived from this and other pooling schemes, and from unpooled electrodes, were subjected to identical statistical analysis of the N170 own-face effect in a Joe/No Joe face recognition paradigm wherein participants monitored for a target face (Joe) presented amongst other unfamiliar faces and their own face. Results between the Joe, unfamiliar face and own face conditions were compared using Cohen's d statistic (square root of signal-to-noise ratio) to measure effect size. RESULTS: When the own-face condition was compared to the Joe and unfamiliar-face conditions, the channel map method increased effect size by a factor ranging from 1.2 to 2.2. These results stand in contrast to previous findings, where conventional pooling schemes failed to reveal an N170 effect to the own-face stimulus (Tanaka JW, Curran T, Porterfield A, Collins D. The activation of pre-existing and acquired face representations: the N250 ERP as an index of face familiarity. J Cogn Neurosci 2006;18:1488-97). Consistent with conventional pooling schemes, the channel map approach showed no reliable differences between the Joe and Unfamiliar face conditions, yielding a decrease in effect size ranging from 0.13 to 0.75. CONCLUSIONS: By increasing the signal-to-noise ratio in the measured waveforms, the channel pool method demonstrated an enhanced sensitivity to the neurophysiological response to own-face relative to other faces. SIGNIFICANCE: By overcoming the characteristic inter-subject variations of ICA, this work allows classic ERP analysis methods to exploit the improved signal-to-noise ratio obtainable with ICA.