Do contaminants compromise the use of recycled nutrients in organic agriculture? A review and synthesis of current knowledge on contaminant concentrations, fate in the environment and risk assessment.

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

A novel native collagen dressing with advantageous properties to promote physiological wound healing.

OBJECTIVE: Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts. Matrix metalloproteinase (MMP) binding was analysed, and the effect of the wound dressings on platelet-derived growth factor B homodimer (PDGF-BB) was investigated. RESULTS: Unlike oxidised regenerated cellulose (ORC)/collagen matrix and ovine forestomach matrix (OFM), the three-dimensional structure of the native collagen matrix (NCM) was found to be analogous to intact, native, dermal collagen. Fibroblasts seeded on the NCM showed exponential growth whereas in ORC/collagen matrix or OFM, very low rates of proliferation were observed after 7 days. MMP sequestration was effective and significant in the NCM. In addition, the NCM was able to significantly stabilise PDGF-BB in vitro. CONCLUSION: We hypothesise that the observed microstructure of the NCM allows for an effective binding of MMPs and a stabilisation and protection of growth factors and also promotes the ingrowth of dermal fibroblasts, potentially supporting the re commencement of healing in previously recalcitrant wounds. DECLARATION OF INTEREST: This work was supported by BSN Medical, Hamburg, Germany.

Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.

BACKGROUND: T-cell responses contribute to the anti-tumoural effect of photodynamic therapy (PDT). For such responses to occur, dendritic cells (DCs) have to migrate to the tumour, take up tumour antigens and respond to danger signals with maturation, before they engage in T-cell activation. Here, we have studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DCs in vitro in a human spheroid model of glioblastoma (GB). METHODS: Spheroids of the GB cell lines U87 and U251 were treated with ALA/PDT, and effects on attraction, uptake of tumour antigens and maturation of DCs were studied. To block heat-shock protein-70 (HSP-70) on the spheroids, neutralising antibodies were used. RESULTS: 5-Aminolevulinic acid /PDT-treated GB spheroids attracted DCs that acquired tumour antigens from the spheroids effectively. Moreover, co-culture with ALA/PDT-treated spheroids induced DC maturation as indicated by the upregulation of CD83 and co-stimulatory molecules as well as increased T-cell stimulatory activity of the DCs. Heat-shock protein-70 was upregulated on the spheroids after ALA/PDT treatment. Uptake of tumour antigens and DC maturation induced by the ALA/PDT-treated spheroids were inhibited when HSP-70 was blocked. CONCLUSION: ALA/PDT treatment of glioma spheroids promotes the three initial steps of the afferent phase of adaptive immunity, which is at least partially mediated by HSP-70.

Chemokines and inflammatory skin diseases.

Accumulating evidence indicates that chronically relapsing inflammatory skin diseases such as atopic dermatitis and psoriasis are T cell-mediated diseases. Thus, understanding the underlying mechanisms of memory T-cell homing to the skin may provide promising targets for the development of novel therapeutics to interfere with inflammatory processes of the skin. Chemokines, a superfamily of small cytokine-like, chemotactic proteins, have recently been shown to critically regulate leukocyte trafficking. Here we summarize results of recent studies associating chemokines with a psoriatic or atopic dermatitis phenotype and delineating their role in the recruitment of memory T cells to the skin.