Pyrrolizidine alkaloids in food and phytomedicine : Occurrence, exposure, toxicity, mechanisms, and risk assessment - A review

Among naturally occurring plant constituents, the 1,2-unsaturated pyrrolizidine alkaloids (in the following termed ‘PAs’) play a distinct role because of the large number of congeners occurring in nature and the pronounced toxicity of some congeners. Several PAs are hepatotoxic in humans, experimental and farm animals and were shown to be potent hepatocarcinogens in laboratory rodents. Although the general mode of action leading to toxicity has been elucidated, i.e., being mediated by metabolic conversion of the parent molecule into a highly reactive electrophile capable of attacking cellular target molecules, major questions related to the risk assessment of PAs remain unresolved. It was the aim of a workshop held in September 2018 to shed more light on the occurrence, exposure, mode of action, toxicokinetics and –dynamics of PAs to improve the scientific basis for an advanced toxicological risk assessment. The contributions in nine chapters describe the scientific progress using advanced analytical methods, studies in subcellular fractions, cell culture, experimental animals and humans and the use of PBPK modeling and structure-activity relationship considerations aiming at a better understanding of PA toxicity and genotoxicity. Since PAs differ considerably in their toxic potencies and substantial species differences in sensitivity towards PA exposure exist, a special emphasis was placed on these issues.</p

Low prevalence of SARS-CoV-2 detected in symptomatic children admitted to hospital

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in 2019 and is responsible for the condition known as COVID-19. COVID-19 was first reported in Ireland in February 2020 with University Hospital Limerick’s (UHL) first paediatric case reported on 4th March 2020. Studies have shown clinical manifestations of children’s cases are generally less severe than those of adults. UHL serves a catchment population of approximately 100,000 children. We aimed to describe the clinical presentation, and prevalence of SARS-CoV-2, in children requiring inpatient hospitalization during the initial phase of the pandemic in Ireland. Methods Data were examined relating to all inpatients aged 0 – 16 years admitted with a queried or confirmed diagnosis of COVID-19 from 8 th February 2020 to 8th June 2020. Emergency Department notes and inpatient records along with laboratory and radiology records were reviewed. Results 220 paediatric inpatients were tested by PCR for SARS-CoV-2 during this period; 101 (45.9%) were female. Ninety-five (43.2%) were diagnosed with ‘viral illnesses’. Seven (3.2%) had laboratory confirmed SARS-CoV-2, with an average age of 8.1 years (range: 0.59 years to 13.77 years). There were two Kawasaki-like illnesses admitted; both tested negative for SARS-CoV-2 on PCR. In our SARS-CoV-2 positive cohort, there was no associated significant morbidity and no associated mortality. Conclusion During the initial phase of the COVID-19 pandemic, prevalence of confirmed SARS-CoV-2 in symptomatic hospitalised children was low at 3.2