Search

Introduction: In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center., Methods: A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure)., Results: The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10-17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries)., Discussion: This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data., Conclusions: Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population.

Purpose: The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic., Methods: A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs. All DSPs among adolescents with the age of 13 up to and including 17 years were included. DSP characteristics included: age, gender, bodyweight, used substance, dose, and treatment advice. Trends in the number of DSPs were analyzed using time series decomposition and Seasonal Autoregressive Integrated Moving Average models., Results: Six thousand nine hundred fifteen DSPs in adolescents were recorded from January first 2016 until December 31st 2021. Females were involved in 84% of adolescent DSPs. A strong increase in the number of DSPs was observed in 2021 (45% increase compared to 2020), which deviated from the predicted trend based on previous years. This increase was most prominent in 13-, 14-, and 15-year-old female adolescents. Commonly involved drugs were paracetamol, ibuprofen, methylphenidate, fluoxetine, and quetiapine. The contribution of paracetamol rose from 33% in 2019 to 40% in 2021., Discussion: The strong increase in the number of DSPs during the second year of the COVID-19 pandemic suggests that long-term containment measures such as quarantines, lockdowns, and school closures may enhance self-harm behavior among adolescents, especially among younger females (13-15 years of age), with a preference for paracetamol as DSP substance., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The accidental ingestion of diluted household descaling products by infants is a phenomenon that poison control centers regularly encounter. Feeding infants with baby milk prepared with water from electric kettles still containing descaler is a common way of exposure. This study aimed to determine the risks related to ingestion of (diluted) descalers by infants., Methods: pH measurements were performed using acetic acid and three different commercially available electric kettle descalers. The pH of different dilutions was measured in the absence or presence of baby milk powder. In addition, an overview was made of pH values of different electric kettle descalers as given by the product information of the manufacturer. Finally, a simple pharmacokinetic (PK) model was used to predict changes in blood pH in infants after ingestion of acetic acid, which is the most commonly used descaler., Results: Several commercially available electric kettle descalers have a pH <2. Even after diluting such descalers up to 10 times the pH can remain low. The addition of milk powder increases the pH of descalers containing weaker acids, with a pH >1.5, while descalers with stronger acids and pH <1 show little pH increase after the addition of milk powder. Finally, a simple PBPK model for the ingestion of acetic acid predicted that the ingestion of larger amounts of acetic acid (>1000 mg) by an infant could result in relevant changes in blood pH., Conclusions: Commercially available electric kettle descaling products may pose a health risk to infants in case of accidental ingestion since the pH of some of these products can be very low, even when diluted 10-times or in the presence of baby milk powder. Oral exposure of infants to the common descaler acetic acid, after accidental preparation of baby milk with cleaning vinegar, will probably not result in serious local effects, but changes in blood pH cannot be excluded when larger amounts of acetic acid are ingested.

Nitrate intake in humans is high through intake of vegetables such as beets, lettuce, and spinach. Nitrate itself is a compound of low toxicity but its metabolite, nitrite, formed by bacteria in the oral cavity and gastrointestinal tract, has been suspected of potential carcinogenic effects. Nitrite can induce systemic toxicity only after having been absorbed from the gastrointestinal tract. The aim of this study was to determine the absolute bioavailability of nitrite following oral administration in humans. In an open, three-way cross-over study, nine subjects received two single oral doses of sodium nitrite (0.12 and 0.06 mmol NaNO(2)/mmol Hb) and one intravenous sodium nitrite dose (0.12 mmol NaNO(2)/mmol Hb). Plasma samples were analysed to assess the nitrite levels, and pharmacokinetic parameters were calculated. Nitrate and methaemoglobin levels in plasma were also measured as oxidation of nitrite results in the formation of these two compounds. Absolute bioavailability of nitrite was 98% after oral administration of 0.12 mmol NaNO(2)/mmol Hb, and 95% after oral administration of 0.06 mmol NaNO(2)/mmol Hb. Minor adverse effects were observed after the 0.12 mmol NaNO(2)/mmol Hb oral dose. In conclusion, nitrite in solution is highly absorbed from the gastrointestinal tract and the first pass effect in the liver is low.

High dietary nitrate intake may pose a risk to human health. Since up to 80-85% of dietary nitrate intake comes from vegetables, the aim of this study was to determine the absolute bioavailability of nitrate from three nitrate-rich vegetables. In an open, four-way cross-over, single dose study, 12 human subjects underwent the following treatments: (1) intravenous infusion of 500mg sodium nitrate, (2) oral administration of 300g cooked spinach, (3) oral administration of 300g raw lettuce, and (4) oral administration of 300g cooked beetroot. The wash-out period between treatments was at least 6 days. Plasma samples were analysed to assess the nitrate and nitrite concentrations, and pharmacokinetic parameters were calculated. The bioavailability of nitrate was 98+/-12% from cooked spinach, 114+/-14% from raw lettuce and 106+/-15% from cooked beetroot. There was no significant increase in plasma nitrite concentrations. This study shows that nitrate from vegetables, whether cooked or uncooked, is absorbed very effectively, resulting in an absolute nitrate bioavailability of around 100%. Thus, reducing the amount of nitrate in vegetables can be an effective measure to lower the systemic nitrate exposure of the general population. However, other aspects, such as the costs to produce vegetables with a low nitrate content and the possible beneficial effects of nitrate in vegetables, need to be considered when evaluating the usefulness of such a measure.

Introduction: Serious intoxications associated with low doses of imidazolines have been reported. Therefore, the treatment advice for children with xylometazoline overdose is usually to observe the child in the hospital, even after exposure to very low doses. Our aim was to determine the frequency of severe symptoms after xylometazoline exposure, and the systemic dose of xylometazoline below which asymptomatic children do not need to be hospitalized for observation., Methods: From May 2002 until December 2004, we prospectively collected data on all consecutive cases of xylometazoline exposure in children <6 years old reported to our poisons centre. Follow-up information was collected. The systemic dose was calculated and the frequency of severe symptoms was observed., Results: During 32 months, we included 101 cases of xylometazoline exposure in children. For 63 out of these 101 cases, follow-up information could be collected. No severe symptoms were observed after exposure to xylometazoline doses reported to be below 0.4 mg/kg (95% confidence interval: 0-6%)., Conclusion: We conclude that less than 6% of children exposed to xylometazoline, at doses reported to be less than 0.4 mg/kg body weight, may develop symptoms that require hospitalization.

Scavenger receptor class A (SR-A) facilitates the development of atherosclerosis, which might be due to its role in the uptake of modified low-density lipoproteins. However, the receptor is also suggested to be important for cell adhesion, thereby potentially influencing the residence time of cells in vivo. Using SR-A-deficient mice, we investigated the role of SR-A in the adhesion of peritoneal macrophages (PM) and tissue macrophages (Kupffer cells). In resident PM no effect of the absence or presence of SR-A on cell adhesion was observed, either in the presence or in the absence of serum. However, in thioglycollate-induced PM, SR-A is important for adhesion both in the presence and in the absence of serum and more than 85% of the divalent-cation-independent adhesion in the presence of serum is mediated by SR-A. In unactivated Kupffer cells, like in resident PM, adhesion is not influenced by the absence or presence of SR-A. In vivo administration of phorbol 12-myristate 13-acetate leads to the activation of Kupffer cells, and it appears that under these conditions SR-A does contribute to adhesion, since both in the absence and in the presence of serum SR-A is responsible for about 35% of cell adhesion. It is concluded that SR-A is important for the divalent-cation-independent adhesion of activated PM and Kupffer cells, suggesting that SR-A may influence the residence time of cells at sites of cellular activation, e.g., in atherosclerotic plaques and during liver infection., (Copyright 1999 Academic Press.)

The adaptation of an existing industrial production line to boost production capacity (a hardware analogue of strain improvement) or to enable the production of a derivative of the original product is used as an example to explore the similarities between process design and engineering and metabolic pathway engineering. In the two fields the same principles appear to apply: for most process engineering solutions metabolic pathway engineering analogues can be found. Analogues are illustrated by reference to literature (e.g. overproduction of amino acid precursors at the 'bottom' of the pathway, relocalisation of proteins and overexpression of genes from the secondary metabolism). Some possible future applications are defined (e.g. supervisory manipulations as regulation by gene transcription factors).

Rat liver Kupffer cell membranes contain a protein that recognizes specifically oxidized low-density lipoproteins (oxLDL). Visualization after blotting under reducing conditions indicates that the receptor is a monomeric protein, with an estimated molecular mass of 115-120 kDa. N-Glycosidase F and endoglycosidase F treatment resulted in a fall in estimated molecular mass of 24 and 11 kDa respectively, whereas O-glycosidase was ineffective. No effect on the extent of interaction with oxLDL was noticed, suggesting that glycans are not essential for ligand recognition. Using a polyclonal antibody to mouse macrosialin, we visualized macrosialin on blot, and compared this glycoprotein with the oxLDL-binding protein. It appears that the two glycoproteins have a similar molecular mass and are comparably affected by treatment with the different glycosidases. Incubation with trypsin resulted in a reduction in the estimated molecular mass of about 25 kDa for both the oxLDL-binding protein and macrosialin. These results indicate that the oxLDL-binding protein and macrosialin are identical, suggesting a role for macrosialin in modified LDL catabolism.

The liver plays a decisive role in the regulation of the plasma levels of atherogenic lipoproteins. The primary liver interaction site for chylomicron-remnants and VLDL remnants (beta-VLDL) is still unidentified, while the subsequent cellular uptake is likely to be mediated in concert by the LDL receptor related protein (LRP) and the LDL receptor. The nature of the primary interaction site of remnants (remnant-receptor) might be a liver-specific proteoglycan or a liver-specific protein. Atherogenic modified LDL can be recognized by a family of scavenger-receptors. A newly identified 95-kDa protein forms the most likely candidate for mediating the in vivo uptake of oxidized LDL from the circulation and might thus protect the body against the presence of oxidized LDL in the blood compartment.

Addition of epidermal growth factor to A431 cells results in dramatic changes in cell morphology. Initially the cells form membrane ruffles accompanied by increased actin polymerization, followed by cell rounding. Activation of the tyrosine kinase of the receptor by binding epidermal growth factor leads also to phosphorylation and activation of phospholipase C-gamma 1, a key enzyme in the phosphoinositide pathway. In this study we have investigated the localization of phospholipase C-gamma 1 during cell activation by epidermal growth factor. It is shown that addition of the growth factor to A431 cells leads to a translocation of phospholipase C-gamma 1 from the cytosol to the membrane fraction. Interestingly, this relocation is exclusively directed to the membrane ruffles. Most of the phospholipase C-gamma 1 associates to the membrane and a small fraction to the underlying skeleton. Immunocytochemical studies demonstrated that phospholipase C-gamma 1 co-localizes with the epidermal growth factor receptor and also filamentous actin at the membrane ruffles. Moreover, using anti-phosphotyrosine antibodies we found that the membrane ruffles are significantly enriched in phosphotyrosyl proteins. Between 5 and 10 minutes after stimulation the membrane ruffles disappear and also the co-localization of phospholipase C-gamma 1 with the epidermal growth factor receptor and filamentous actin. These results support the notion that activation of A431 cells by epidermal growth factor leads to the formation of a signalling complex of its receptor, phospholipase C-gamma 1 and filamentous actin which is primarily localized at membrane ruffles.