Environmental quality standards for diclofenac derived under the European Water Framework Directive: 1. Aquatic organisms

Diclofenac is a nonsteroidal anti-inflammatory human and veterinary medicine widely detected in European surface waters, especially downstream from Wastewater Treatment Plants (WWTPs). Veterinary uses of diclofenac in Europe are greatly restricted, so wastewater is the key exposure route for wildlife. Proposed Environmental Quality Standards (EQS) which include an assessment of toxicity to aquatic organisms are under consideration by the European Commission (EC) to support the aims of the Water Framework Directive (WFD). The EC approach favours the use of a deterministic (single test value and an assessment factor) approach to the derivation of a direct toxicity EQS for diclofenac, resulting in an EQS of 0.040 µg L−1 based on a single mesocosm study. In this paper, we discuss potential issues with this approach with respect to the EC’s own guidance on EQS derivation and derive an evidence-driven alternative EQS of 0.126 µg L−1 using a probabilistic (species sensitivity distribution) approach that accounts for all of the reliable and relevant data and is in accordance with the guidance. Europe-wide freshwater monitoring data for diclofenac are used in an indicative compliance assessment using the EC and the alternative evidence-driven EQS. The implications of using only some data to derive an EQS that does not adhere to the guidance, compared to a guidance-compliant approach that uses all the data available are also discussed.

Screening of antibiotic residues in raw milk of cows and buffalos by diffusion assays

Although antibiotics are valuable drugs for treatment of certain infections, their presence in foodstuff derived from animals is a potential public health hazard. They pose a serious threat as they are implicated in direct toxicity; allergic reactions; disturbance of the normal gut microbiota, carcinogenesis, and emergence of antibioticresistant bacteria. This study investigated the occurrence of antibiotic residues in raw milk samples derived from cows and buffaloes. Samples were collected randomly from different retail outlets in Erbil city (Iraq) from January 1st to June 30th, 2019. The residues were detected by two diffusion assays against Bacillus subtilis bacteria on agar plates. The total occurrence of residues ranged from 11.9% to 13.4% of screened milk samples. No significant differences were found between milk type or location of animal rearing (urban or suburban). Regarding the seasonal variations, spring was found to be associated with gradual decrease in antibiotic residues levels in milk. Such occurrence rate of residues is alarming and require authorities to observe the quality of raw milk introduced to markets for consumption. Further evaluation of antibiotic stability period in raw milk is also necessary.

Environmental quality standards for diclofenac derived under the european water framework directive: 1. Aquatic organisms

Diclofenac is a nonsteroidal anti-inflammatory human and veterinary medicine widely detected in European surface waters, especially downstream from Wastewater Treatment Plants. Veterinary uses of diclofenac in Europe are greatly restricted, so wastewater is the key exposure route for wildlife. Proposed Environmental Quality Standards (EQS) which include an assessment of toxicity to aquatic organisms are under consideration by the European Commission (EC) to support the aims of the Water Framework Directive (WFD). The EC approach favours the use of a deterministic (single test value and an assessment factor) approach to the derivation of a direct toxicity EQS for diclofenac, resulting in an EQS of 0.040 µg L− 1 based on a single mesocosm study. In this paper, we discuss potential issues with this approach with respect to the EC’s own guidance on EQS derivation and derive an evidence-driven alternative EQS of 0.126 µg L− 1 using a probabilistic (Species Sensitivity Distribution) approach that accounts for all of the reliable and relevant data and is in accordance with the guidance. Europe-wide freshwater monitoring data for diclofenac are used in an indicative compliance assessment using the EC and the alternative evidence-driven EQS. The implications of using only some data to derive an EQS that does not adhere to the guidance, compared to a guidance compliant approach that uses all the data available is also discussed.

Development of a chitosan and hyaluronic acid hydrogel with potential for bioprinting utilization: A preliminary study

Bioprinting is a technique that has been applied in the areas of tissue engineering and regenerative medicine (TERM). Natural polymer-based hydrogels are known for their favorable biocompatible properties, as well as attractive biomaterials for cell encapsulation. These hydrogels provide an aqueous three-dimensional environment with biologically relevant chemical and physical signals, mimicking the natural environment of the extracellular matrix (ECM). Chitosan (CHI) and hyaluronic acid (HA) have been widely researched for biomedical applications. Bioinks are “ink” formulations, usually hydrogels, that allow the printing of living cells. This work proposes the development of a low cost and simple chitosan CHI-AH hydrogel with potential to become a bioink. At physiological temperature, the biomaterials form a hydrogel. The material developed was characterized by the analysis of morphology, cytotoxicity, and cell viability. FTIR showed the characteristic vibrational bands of chitosan and HA. No difference in swelling was observed between the different formulations studied, although SEM showed architectural differences between the hydrogels obtained. Extract cytotoxicity testing showed that the hydrogel is not cytotoxic. The direct toxicity test also revealed the absence of toxicity, but the cells had difficulty migrating into the gel, probably because of its density. These data were confirmed by SEM. Further testing are ongoing to better understand the gel’s characteristics to improve the limitations found so far.

What’s Eating You? Black Butterfly (Hylesia nigricans)

Lepidopterism refers to the adverse medical effects of contact with insects of the order Lepidoptera, which includes both moths and butterflies. These effects typically result from contact with an insect during the caterpillar (larval) stage. Lepidopterism involves multiple pathologic mechanisms, including direct toxicity of venom and mechanical irritant effects. Clinical patterns associated with contact with lepidoptera include localized stinging reactions, papular urticaria and dermatitis, urticarial wheals, and hemorrhagic diathesis. Accurate diagnosis of symptoms associated with contact with caterpillars, butterflies, or moths is nearly impossible without a reliable history of exposure, as the histology of exposure is nonspecific. Treatment is largely empiric and should be based on symptoms. We report a case of lepidopterism in a patient with acute cutaneous lesions following exposure to an adult-stage black butterfly (Hylesia nigricans).

High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells

Mortality of patients with end-stage renal disease tremendously exceeds that of the general population due to excess cardiovascular morbidity. Large middle-sized molecules (LMM) including pro-inflammatory cytokines are major drivers of uremic cardiovascular toxicity and cannot be removed sufficiently by conventional high-flux (HFL) hemodialysis. We tested the ability of plasma from 19 hemodialysis patients participating in a trial comparing HFL with high cut-off (HCO) membranes facilitating removal of LMM to induce calcification in mesenchymal stromal cells (MSC) functioning as vascular progenitors. HCO dialysis favorably changed plasma composition resulting in reduced pro-calcific activity. LMM were removed more effectively by HCO dialysis including FGF23, a typical LMM we found to promote osteoblastic differentiation of MSC. Protein-bound uremic retention solutes with known cardiovascular toxicity but not LMM inhibited proliferation of MSC without direct toxicity in screening experiments. We could not attribute the effect of HCO dialysis on MSC calcification to distinct mediators. However, we found evidence of sustained reduced inflammation that might parallel other anti-calcifying mechanisms such as altered generation of extracellular vesicles. Our findings imply protection of MSC from dysfunctional differentiation by novel dialysis techniques targeted at removal of LMM. HCO dialysis might preserve their physiologic role in vascular regeneration and improve outcomes in dialysis patients.

May propylthiouracil induce autoimmune-related immunotoxicity?

Introduction. The use of propylthiouracil can be associated with mild adverse reactions, but severe complications like agranulocytosis and vasculitis can also be seen. Direct toxicity and immune-mediated induction of anti-neutrophile cytoplasmic antibodies have been described as possible mechanisms responsible for agranulocytosis. The majority of vasculitis are antimyeloperoxidase antibodies associated, but the exact mechanism for anti-neutrophile cytoplasmic antibodies-associated vasculitis as an adverse effect of propylthiouracil treatment is still unclear. Case report. Here we present a case of a female patient who presented with fever and throat pain two weeks after propylthiouracil therapy was initiated. Agranulocytosis alongside with basal left sided pneumonia was noted. Propylthiouracil was discontinued, and the treatment with broad spectrum antibiotics was started, as well as Lugol?s solution, methylprednisolone, and granulocyte-colony stimulating factor. The following course of treatment was complicated by the occurrence of a generalized erythematous-papullomatous rash. The patient was diagnosed with agranulocytosis and antimyeloperoxidase, anti-neutrophile cytoplasmic antibodies positive vasculitis as an adverse effect of propylthiouracil. Conclusion. Patients presenting with concomitant agranulocytosis and anti-neutrophile cytoplasmic antibodies-associated vasculitis as a complication of propylthiouracil therapy for Graves?s disease are rare in clinical practice. Prompt discontinuation of antithyroid drug is of great importance. Similarities in the pathogenesis of both conditions could be the potential explanation for these two adverse events occurring at the same time which points out to the need for a deeper understanding of this topic.

Effect of high-temperature extracted plant material fume against southern cowpea weevil (Callosobruchus chinensis L.) (Coleoptera: Bruchidae) as a non-chemical novel fumigation technique

Background Fumes from high-temperature heated plant leaves containing volatile phytochemicals generated from Lantana camara, Cinnamomum zeylanicum, Azadirachta indica and Ocimum sanctum were tested for their insecticidal activity against adult southern cowpea weevil (Callosobruchus chinensis L.) and their F1 progeny production/emergence. Volatile phytochemicals containing fume was generated using a flameless dry heat extraction method similar to pyrolysis combustion without air supplement at 180 ± 5 °C. Insect mortalities were assessed up to 72 h after exposure to the different treatments of fumigation by plant-fume and control. Results All volatile plant-fume samples contained average of 16.3 ± 1.5% O2 and 5.8 ± 0.5% CO2 in the test jars. The F1 progeny emergence was estimated 30 days after treatment. After 36 h of exposure, L. camara showed the highest toxicity against C. chinensis, followed by O. sanctum, A. indica and C. zeylanicum, with LT50 values of 7.3, 9.4, 14.7 and 20.6 h, respectively. The volatile phytochemical containing plant-fume generated by A. indica and C. zeylanicum produced LT99 values that were not significantly different (P > 0.05) from each other. The F1 adult emergence from treated mungbean (Vigna radiata L.) samples was significantly inhibited by L. camara and A. indica volatile plant-fume compared to C. zeylanicum fume. However, plant-fume generated from all four plants exhibited effective direct toxicity and F1 progeny inhibition of more than 86%. Conclusion From the study, it can be concluded that volatile plant-fume treatment was highly lethal to C. chinensis and significantly reduced F1 progeny emergence. Therefore, phytochemicals obtained from thermal extraction technique can be used as an alternative technique to chemical fumigation of stored mungbean.

Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explored the indirect effects of NPs, through consequences due to the exposure of neighboring cells to NPs. In this study, we analysed possible direct and indirect effects of NPs (polyacrylic acid (PAA) coated cobalt ferrite NP, TiO2 P25 and maghemite NPs) on immortalized mouse microglial cells and differentiated CAD mouse neuronal cells in monoculture (direct toxicity) or in transwell co-culture system (indirect toxicity). We showed that although the low NP concentrations (2–25 µg/mL) did not induce changes in cell viability, cytokine secretion or NF-κB activation of microglial cells, even low NP concentrations of 10 µg/mL can affect the cells and change their secretion of protein stress mediators. These can in turn influence neuronal cells in indirect exposure model. Indirect toxicity of NPs is an important and not adequately assessed mechanism of NP toxicity, since it not only affects cells on the exposure sites, but through secretion of signaling mediators, can also affect cells that do not come in direct contact with NPs.

2,4-EPIBRASSIONOLIDE ACTIVATES PRIMING RESISTANCE AGAINST RHIZOPUS STOLONIFER INFECTION IN PEACH FRUIT

This study was conducted to assess the effects of 2,4-epibrassionolide (EBR) on mold decay caused by Rhizopus stolonifer and its capability to activate biochemical defense reactions in postharvest peaches. The treatment of EBR at 5 μM possessed the optimum effectiveness on inhibiting the Rhizopus rot in peach fruit among all treatments. The EBR treatment significantly up-regulated the expression levels of a set of defense-related enzymes and PR genes that included PpCHI, PpGns1, PpPAL, PpNPR1, PpPR1 and PpPR4 as well as led to an enhancement for biosynthesis of phenolics and lignins in peaches during the incubation at 20 °C. Interestingly, the EBR-treated peaches exhibited more striking expressions of PR genes and accumulation of antifungal compounds upon inoculation with the pathogen, indicating a priming defense could be activated by EBR. On the other hand, 5 μM EBR exhibited direct toxicity on fungal proliferation of R. stolonifer in vitro. Thus, we concluded that 5 μM EBR inhibited the Rhizopus rot in peach fruit probably by a direct inhibitory effect on pathogen growth and an indirect induction of a priming resistance. These findings provided a potential alternative for control of fungal infection in peaches during the postharvest storage.