Human pharmaceuticals in the arctic - A review.

Pharmaceuticals have been deemed as 'contaminants of emerging concern' within the Arctic and are a potentially perennial form of pollution. With recent innovations in detection technology for organic compounds, researchers have been able to find substantial evidence of the presence and accumulation of pharmaceutical pollution within the Arctic marine ecosystem. The pharmaceuticals, which are biologically active substances used in diagnosis, treatment or prevention of diseases, may persist in the Arctic environment and may have an impact on the resident marine biota. Thus, to understand the standing of current research on the origin, transport, bioaccumulation and impacts of pharmaceutical pollution on the Arctic marine ecosystem, this study collates research from the early 2000s to the end of 2023 to act as a baseline for future research. The study highlights the fact that there is an evident threat to the Arctic marine ecosystem due to pharmaceutical pollution. It also shows that the impacts of pharmaceuticals within the Arctic ocean are not well studied.

Impact of seawater temperature and physical-chemical properties on sorption of pharmaceuticals, stimulants, and biocides to marine particles.

Pharmaceuticals, stimulants, and biocides enter the environment via wastewater from urban, domestic, and industrial areas, in addition to sewage, aquaculture and agriculture runoff. While some of these compounds are easily degradable in environmental conditions, others are more persistent, meaning they are less easily degraded and can stay in the environment for long periods of time. By exploring the adsorptive properties of a wide range of pharmaceuticals, stimulants, and biocides onto particles relevant for marine conditions, we can better understand their environmental behaviour and transport potential. Here, the sorption of 27 such compounds to inorganic (kaolin) and biotic (the microalgae Cryptomonas baltica) marine particles was investigated. Only two compounds sorbed to microalgae, while 23 sorbed to kaolin. The sorption mechanisms between select pharmaceuticals and stimulants and kaolin was assessed through exploring adsorption kinetics (caffeine, ciprofloxacin, citalopram, fluoxetine, and oxolinic acid) and isotherms (ciprofloxacin, citalopram, and fluoxetine). Temperature was shown to have a significant impact on partitioning, and the impact was more pronounced closer to maximum sorption capacity for the individual compounds.

Assessment of Cold Atmospheric Pressure Plasma (CAPP) Treatment for Degradation of Antibiotic Residues in Water.

The presence of antibiotic residues in water is linked to the emergence of antibiotic resistance globally and necessitates novel decontamination strategies to minimize antibiotic residue exposure in both the environment and food. A holistic assessment of cold atmospheric pressure plasma technology (CAPP) for ß-lactam antibiotic residue removal is described in this study. CAPP operating parameters including plasma jet voltage, gas composition and treatment time were optimized, with highest ß-lactam degradation efficiencies obtained for a helium jet operated at 6 kV. Main by-products detected indicate pH-driven peroxidation as a main mechanism of CAPP-induced decomposition of ß-lactams. No in vitro hepatocytotoxicity was observed in HepG2 cells following exposure to treated samples, and E. coli exposed to CAPP-degraded ß-lactams did not exhibit resistance development. In surface water, over 50% decrease in antibiotic levels was achieved after only 5 min of treatment. However, high dependence of treatment efficiency on residue concentration, pH and presence of polar macromolecules was observed.

Recent advances and remaining barriers to producing novel formulations of fungicides for safe and sustainable agriculture.

BACKGROUND: Fungi have evolved for 1 billion years and due to their adaptability and resilience can be found in multiple habitats around the globe. Among numerous species of fungi, some are pathogenic, and humans have battled since the dawn of organized agriculture to reduce production losses. With the arrival of fungicides many gains have been made in this struggle. However, though fungicides have greatly contributed to substantial increase in agricultural productivity, their over usage has led to both health and environmental repercussions. They remain cornerstone of the agriculture industry, however, development of safer formulations to champion sustainable and eco-friendly agriculture is of great importance, especially in face of a growing global population, climate change and increasing fungal resistance to existing compounds. SCOPE AND APPROACH: The aim of this review is to present the state of the art in fungicides formulations developed for agrochemistry, also describing recent improvements in their safety, with special focus on fungicides used most against the ten most important fungal pathogens. KEY FINDINGS AND CONCLUSIONS: The major focus in the field remains to be the improvement of the overall performance of the fungicide formulations. The research trends are also moving towards developing more eco-friendly formulations. However, there are still very few studies assessing nanoformulations toxicity and environmental impact. For example, there is still a limited body of research on the holistic assessment of nanoformulation shells' fate in soil and in the environment after release, as well as redistribution within plants after absorption, with no studies on human or environmental exposure.

The origin of in-vitro estrogen-like activity in oregano herb extracts.

Global market of herbs has been struggling with food adulteration issues. A number of assays have been developed to aid the detection of the tampered samples and ensure high quality of the marketed products. However, herbs are marketed not only for their culinary applications but also as remedies due to high levels of biologically active constituents. Nevertheless, there is no information in the literature about the influence of herbs adulteration on the biological activity of the final product. Current study aims at assessing the influence of oregano adulteration on its in-vitro estrogen-like activity. High responses in a mammalian reporter gene assay have been detected in pure and adulterated samples, translating to 21-7409 ng of 17ß-estradiol equivalents per gram of oregano. The origin of those responses was assessed by combining fractionation and UHPLC-HRMS. Three flavones were proposed as the most active extract constituents i.e. luteolin-glucoside, luteolin- and apigenin-glucuronides all of which have been previously identified in other herbal extracts with estrogenic activity. This study underlines challenges of biological activity assessment in complex herbal extracts as well as the need for further assessment of such supplement administrations in the case of postmenopausal women and breast cancer patients undergoing hormone therapy.

Simultaneous authentication of species identity and geographical origin of shrimps: Untargeted metabolomics to recurrent biomarker ions.

Mandatory disclosure of the species identity, production method, and geographical origin are embedded in the regulations and traceability systems, governing international seafood trade. A high-resolution mass spectrometry-based metabolomics approach could simultaneously authenticate the species identity and geographical origin of commercially important shrimps. The highly innovative approach spared the need for multiple testing methods which are in routine use currently. A robust chemometric model, developed using the metabolite fingerprint dataset, could accurately predict the species identity of the shrimp samples. Subsequently, species-specific biomarkers were discovered and a tandem mass spectrometry method for authentication of the species was developed. Two other chemometric models from the metabolomics experiment accurately predicted the geographical origin of king prawns and tiger prawns. The study has shown for the first time that food-metabolomics along with chemometrics can simultaneously check for multiple seafood fraud issues in the global seafood supply-chain.

Occurrence and Human-Health Impacts of Mycotoxins in Somalia.

Mycotoxins are secondary metabolites produced by various molds that contaminate many staple foods and cause a broad range of detrimental health effects in animals and humans through chronic exposure or acute toxicity. As such, the worldwide contamination of food and feed with mycotoxins is a significant problem, especially in sub-Saharan Africa. In this study, mycotoxin occurrence in staple foods consumed in Somalia was determined. A total of 140 samples (42 maize, 40 sorghum, and 58 wheat) were collected from a number of markets in Mogadishu, Somalia, and analyzed by a UPLC-MS/MS multimycotoxin method that could detect 77 toxins. All of the maize samples tested contained eight or more mycotoxins, with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) levels reaching up to 908 and 17 322 µg/kg, respectively, greatly exceeding the European Union limits and guidance values. The average probable daily intake of fumonisins (FB1 and FB2) was 16.70 µg per kilogram of body weight (kg bw) per day, representing 835% of the recommended provisional maximum tolerable daily intake value of 2 µg/(kg bw)/day. A risk characterization revealed a mean national margin of exposure of 0.62 for AFB1 with an associated risk of developing primary liver cancer estimated at 75 cancers per year per 100 000 people for white-maize consumption alone. The results clearly indicate that aflatoxin and fumonisin exposure is a major public-health concern and that risk-management actions require prioritization in Somalia.

A holistic study to understand the detoxification of mycotoxins in maize and impact on its molecular integrity using cold atmospheric plasma treatment.

The need for safe and quality food, free from the presence of hazardous contaminants such as mycotoxins is an on-going and complex challenge. Cold atmospheric pressure plasma (CAPP) has the potential to contribute to achieving this goal. Decontamination efficacy of CAPP against six of the most common mycotoxins found in foods and feedstuffs was assessed herein. Concentration reduction of up to 66% was achieved in maize for both aflatoxin B1 and fumonisin B1. Degradation products were detected only in the case of aflatoxin B1 and zearalenone and were tested on human hepatocarcinoma cells with no increase in cytotoxicity observed. Analysis of treated maize revealed substantial changes to small molecular mass components of the matrix. While CAPP shows promise in terms of mycotoxin detoxification important questions concerning potential changes to the nutritional and safety status of the food matrix require further investigations.

Chemoprevention in BRCA1 mutation carriers (CIBRAC): protocol for an open allocation crossover feasibility trial assessing mechanisms of chemoprevention with goserelin and anastrozole versus tamoxifen and acceptability of treatment.

INTRODUCTION: BRCA1 mutation carriers have a significant lifetime risk of breast cancer, with their primary risk-reduction option being bilateral mastectomy. Preclinical work from our laboratory demonstrated that in BRCA1-deficient breast cells, oestrogen and its metabolites are capable of driving DNA damage and subsequent genomic instability, which are well-defined early events in BRCA1-related cancers. Based on this, we hypothesise that a chemopreventive approach which reduces circulating oestrogen levels may reduce DNA damage and genomic instability, thereby providing an alternative to risk-reducing surgery. METHODS AND ANALYSIS: 12 premenopausal women with pathogenic BRCA1 mutations and no previous risk-reducing surgery will be recruited from family history clinics. Participants will be allocated 1:1 to two arms. All will undergo baseline breast biopsies, blood and urine sampling, and quality of life questionnaires. Group A will receive goserelin 3.6 mg/28 days by subcutaneous injection, plus oral anastrozole 1 mg/day, for 12 weeks. Group B will receive oral tamoxifen 20 mg/day for 12 weeks. Following treatment, both groups will provide repeat biopsies, blood and urine samples, and questionnaires. Following a 1-month washout period, the groups will cross over, group A receiving tamoxifen and group B goserelin and anastrozole for a further 12 weeks. After treatment, biopsies, blood and urine samples, and questionnaires will be repeated. DNA damage will be assessed in core biopsies, while blood and urine samples will be used to measure oestrogen metabolite and DNA adduct levels. ETHICS AND DISSEMINATION: This study has ethical approval from the Office for Research Ethics Committees Northern Ireland (16/NI/0055) and the Medicines and Healthcare products Regulatory Agency (MHRA) (reference: 32485/0032/001-0001). The investigational medicinal products used in this trial are licensed and in common use, with well-documented safety information. Dissemination of results will be via high-impact journals and relevant national/international conferences. A copy of the results will be offered to the participants and be made available to patient support groups. TRIAL REGISTRATION NUMBER: EudraCT: 2016-001087-11; Pre-results.

Development of a comprehensive analytical platform for the detection and quantitation of food fraud using a biomarker approach. The oregano adulteration case study.

Due to increasing number of food fraud incidents, there is an inherent need for the development and implementation of analytical platforms enabling detection and quantitation of adulteration. In this study a set of unique biomarkers of commonly found oregano adulterants became the targets in the development of a LC-MS/MS method which underwent a rigorous in-house validation. The method presented very high selectivity and specificity, excellent linearity (R2>0.988) low decision limits and detection capabilities (<2%), acceptable accuracy (intra-assay 92-113%, inter-assay 69-138%) and precision (CV<20%). The method was compared with an established FTIR screening assay and revealed a good correlation of quali- and quantitative results (R2>0.81). An assessment of 54 suspected adulterated oregano samples revealed that almost 90% of them contained at least one bulking agent, with a median level of adulteration of 50%. Such innovative methodologies need to be established as routine testing procedures to detect and ultimately deter food fraud.

In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia.

The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor.

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30-60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.