Xenobiotic and Immune-Relevant Molecular Biomarkers in Harbor Seals as Proxies for Pollutant Burden and Effects.

Harbor seals are exposed to increasing pressure caused by anthropogenic activities in their marine environment. Persistent organic pollutants (POPs) and trace elements are hazardous contaminants that accumulate in tissues of harbor seals. POPs and trace elements can negatively affect the immune-system and have been reported, e.g., to increase susceptibility to viral infections in seals. Biomarkers of the xenobiotic metabolism, cytokines, and heat-shock protein as cell mediators of the immune-system were established to evaluate the impact of environmental stressors on harbor seals. Harbor seals (n = 54) were captured on sandbanks in the North Sea during 2009-2012. Health assessments, including hematology, were performed, and RNAlater blood samples were taken and analyzed using quantitative polymerase chain reaction. Normalized transcript copy numbers were correlated to hematology and POP concentration in blood and trace metals in blood and fur. A significant correlation between xenobiotic markers and contaminant burden was found. Significant interrelationships between markers and POP compounds, as well as with season, weight, and hematology values, indicate that biomarkers reflect pollutant exposure and effects. A significant relationship between cortisol levels and heat-shock protein expression was observed indicating stress experienced during restraint of the seals. Interleukin-10 transcription showed significant correlations with trace elements in fur pointing toward immune regulatory effects of metal exposure. The molecular markers prove to be an important noninvasive tool that reflects contaminant exposure and the impact of anthropogenic stressors in seal species. The connection between interleukin-2, xenobiotic markers, and pollutants may indicate immune suppression in animals exposed to contaminants with subsequent susceptibility to inflammatory disease.

Electrocautery Devices With Feedback Mode and Teflon-Coated Blades Create Less Surgical Smoke for a Quality Improvement in the Operating Theater.

Monopolar electrocautery is a fast and elegant cutting option. However, as it creates surgical smoke containing polycyclic aromatic hydrocarbons (PAHs), it may be hazardous to the health of the surgical team. Although new technologies, such as feedback mode (FM) and Teflon-coated blades (TBs), reduce tissue damage, their impact on surgical smoke creation has not yet been elucidated. Therefore, we analyzed the plume at its source.The aim of this study was to evaluate if electrocautery FM and TBs create less surgical smoke.Porcine tissue containing skin was cut in a standardized manner using sharp-edged Teflon-coated blades (SETBs), normal-shaped TBs, or stainless steel blades (SSBs). Experiments were performed using FM and pure-cut mode. Surgical smoke was sucked through filters or adsorption tubes. Subsequently, filters were scanned and analyzed using a spectrophotometer. A high-performance liquid chromatography (HPLC-UV) was performed to detect benzo[a]pyrene (BaP) and phenanthrene as 2 of the most critical PAHs. Temperature changes at the cutting site were measured by an infrared thermometer.In FM, more surgical smoke was created using SSB compared with TBs (P < 0.001). Furthermore, differences between FM and pure-cut mode were found for SSB and TB (P < 0.001), but not for SETB (P = 0.911). Photometric analysis revealed differences in the peak heights of the PAH spectrum. In HLPC-UV, the amount of BaP and phenanthrene detected was lower for TB compared with SSB. Tissue temperature variations increased when SSB was used in FM and pure-cut mode. Furthermore, different modes revealed higher temperature variations with the use of SETB (P = 0.004) and TB (P = 0.005) during cutting, but not SSB (P = 0.789).We found that the use of both TBs and FM was associated with reduced amounts of surgical smoke created during cutting. Thus, the surgical team may benefit from the adoption of such new technologies, which could contribute to the primary prevention of smoke-related diseases.

Cohaerins A and B, azaphilones from the fungus Hypoxylon cohaerens, and comparison of HPLC-based metabolite profiles in Hypoxylon sect. Annulata.

Azaphilones, named cohaerins A and B were isolated from stromata of the xylariaceous ascomycete Hypoxylon cohaerens. Their absolute structures were determined by spectroscopic methods (2D NMR, MS, IR, UV CD), and subsequently confirmed by acetylation. Stromatal metabolite profiles of several taxa of Hypoxylon sect. Annulata were also generated using analytical HPLC with diode array and MS detection. The cohaerins were neither found in other Hypoxylon spp., nor in other Xylariaceae. However, they were present even in holotype material of H. cohaerens, collected over 200 years ago. The binaphthalene BNT was also omnipresent in sect Annulata, and its derivatives, the benzo[j]fluoranthenes daldinone A and truncatone, as well as presumably related compounds. These fungi were found devoid of other types of azaphilone pigments of the Xylariaceae, such as mitorubrins and daldinins, the latter of which are widespread in certain groups of Hypoxylon sect. Hypoxylon. Hence, chemotaxonomic data largely support the current generic concept. The original source of truncatone was identified as Hypoxylon annulatum.

Novel analgesic triglycerides from cultures of Agaricus macrosporus and other basidiomycetes as selective inhibitors of neurolysin.

The agaricoglycerides are a new class of fungal secondary metabolites that constitute esters of chlorinated 4-hydroxy benzoic acid and glycerol. They are produced in cultures of the edible mushroom, Agaricus macrosporus, and several other basidiomycetes of the genera Agaricus, Hypholoma, Psathyrella and Stropharia. The main active principle, agaricoglyceride A, showed strong activities against neurolysin, a protease involved in the regulation of dynorphin and neurotensin metabolism (IC50 = 200 nM), and even exhibited moderate analgesic in vivo activities in an in vivo model. Agaricoglyceride monoacetates (IC50 = 50 nM) showed even stronger in vitro activities. Several further co-metabolites with weaker or lacking bioactivities were also obtained and characterized. Among those were further agaricoglyceride derivatives, as well as further chlorinated phenol derivatives such as the new compound, agaricic ester. The characteristics of the producer organisms, the isolation of bioactive metabolites from cultures of A. macrosporus, their biological activities, and preliminary results on their occurrence in basidiomycetes, are described.

Revision of the structures assigned to the fungal metabolites boletunones A and B.

[structure: see text] The structures recently assigned to the mushroom metabolites boletunones A (1) and B (2) are revised to those of 15-methoxycyclocalopin A (5) and isocyclocalopin A (6), respectively.

Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata.

Monorden (1) and the novel resorcylic acid lactones pochonins A (2), B (4), C (6), D (7), and E (8) as well as tetrahydromonorden (5) and pseurotin A (22) were isolated from cultures of the clavicipitaceous hyphomycete Pochonia chlamydosporia var. catenulata strain P 0297. Fermentation of P 0297 in bromide-containing culture media led to a shift in secondary metabolite production and yielded monocillins III (3) and II (9) as major metabolites besides monorden (1) as well as the novel compounds pochonin F (10) and a monocillin II glycoside (11) as minor metabolites. Most of these compounds showed moderate activities in a cellular replication assay against Herpes Simplex Virus 1 (HSV1) and against the parasitic protozoan Eimeria tenella. In contrast to the structurally related zearalenone derivatives none of the metabolites of strain P 0297 were found to be active in a fluorescence polarization assay for determination of modulatory activities on the human estrogenic receptor ERbeta. Beta-zearalenol (17), but not zearalenone (15) and alpha-zearalenol (16), showed antiherpetic effects. We report the production, isolation, and structure elucidation of compounds 1-11 and their biological characterization.

Activities of prenylphenol derivatives from fruitbodies of Albatrellus spp. on the human and rat vanilloid receptor 1 (VR1) and characterisation of the novel natural product, confluentin.

Several prenylphenols from basidiocarps of European and Chinese Albatrellus spp., namely grifolin (1), neogrifolin (2), confluentin (3), scutigeral (4), and albaconol (5) were investigated concerning their activities in test models for vanilloid receptor modulation. The isolation of these compounds from A. confluens and structure elucidation of the novel natural product confluentin (3) are described. The effects of scutigeral and neogrifolin on vanilloid receptors were studied by means of electrophysiological methodology on rat dorsal root ganglion neurons as well as on recombinant cell lines expressing the rat VR1 receptor. Concurrently, the effects of compounds 1-5 on a reporter cell line expressing the human vanilloid receptor VR1 were measured. In contrast to previous studies reported in the literature, the results of these investigations suggest that fungal prenylphenols act as weak antagonists (activity in the microM range), rather than exhibiting agonistic activities.

Altersetin, a new antibiotic from cultures of endophytic Alternaria spp. Taxonomy, fermentation, isolation, structure elucidation and biological activities.

A novel antibacterial antibiotic, for which the name altersetin is proposed, was isolated from the culture broth of two endophytic Alternaria species. The relative and absolute configuration were assigned by NOESY or CD data, respectively. Altersetin is chemically related to equisetin and showed potent MIC against several pathogenic gram-positive bacteria, whereas gram-negative bacteria and pathogenic yeast were not or much less susceptible. Moderate in vivo efficiacy was observed for altersetin in a murine sepsis model.