Calcium kinetic rates in Caucasian males and females from birth to adulthood.

Calcium plays an important role in bone physiology and its kinetics change over lifetime. The analysis of calcium deposition and release through stable isotope techniques has guided recommendations on nutritional uptake for overall health. In addition, calcium kinetics have great relevance for toxicokinetic studies of bone-seeking elements (e.

Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

Background: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents.

Methods: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics.

International Nonproprietary Names (INN) for novel vaccine substances: A matter of safety.

International Nonproprietary Names (INN) are assigned by the World Health Organization (WHO) to pharmaceutical substances to ensure global recognition by a unique name. INN facilitate safe prescribing through naming consistency, efficient communication and exchange of information, transnational access and pharmacovigilance of medicinal products. Traditional vaccines such as inactivated or live-attenuated vaccines have not been assigned INN and provision of a general name falls within the scope of the WHO Expert Committee on Biological Standardization (ECBS).

Physiology-based toxicokinetic modelling of aluminium in rat and man.

A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al, both in animals and man. These limitations are absent in studies with Al as a tracer, but tissue data are limited to animal studies.

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation.

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.

Background: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.

Methods: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.

The Emerging Therapeutic Potential of Nitro Fatty Acids and Other Michael Acceptor-Containing Drugs for the Treatment of Inflammation and Cancer.

Nitro fatty acids (NFAs) are endogenously generated lipid mediators deriving from reactions of unsaturated electrophilic fatty acids with reactive nitrogen species. Furthermore, Mediterranean diets can be a source of NFA. These highly electrophilic fatty acids can undergo Michael addition reaction with cysteine residues, leading to post-translational modifications (PTM) of selected regulatory proteins.

Transferability study of the BINACLE (binding and cleavage) assay for in vitro determination of botulinum neurotoxin activity.

The muscle-relaxing effects of the botulinum neurotoxin (BoNT) serotypes A and B are widely used in clinical and aesthetic medicine. The standard method for measuring the biological activity of pharmaceutical BoNT products is a mouse bioassay. In line with the European Directive 2010/63/EU, a replacement by an animal-free method would be desirable.

Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting.

Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g.

Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats.

Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.

Is the test for irreversibility of tetanus toxoids still relevant?

Tetanus vaccines for human and veterinary use are based on toxoids resulting from a formaldehyde-mediated inactivation of tetanus neurotoxin (TeNT). Due to the high toxicity of TeNT, safety tests are mandatory for each batch of these toxoids. One of the tests addresses the irreversibility of inactivation: The toxoid is stored at 37 °C for 6 weeks and then subjected to in vivo toxicity testing.

Linking Scattered Stem Cell-Based Data to Advance Therapeutic Development.

The biomedical field has witnessed remarkable advances in analytical tools and technologies that have expanded our understanding of healthy and diseased human tissue and, at the same time, enable extensive molecular characterization of living cells. The volume of scientific data generated is expanding in an unprecedented manner; however, these data remain scattered across research groups worldwide. Access to various data sources in a systematic fashion could hugely benefit the progress of nascent fields such as stem cell-based therapeutics.

Aluminium toxicokinetics after intramuscular, subcutaneous, and intravenous injection of Al citrate solution in rats.

Knowledge of dose linearity, plasma clearance, rate and extent of subcutaneous (SC) and intramuscular (IM) absorption of soluble aluminium (Al) citrate is considered a prerequisite for evaluation of toxicokinetic data obtained from SC or IM administration of Al adjuvants in medicinal products. Therefore, total Al plasma kinetics was investigated after SC, IM, and IV administration of single Al doses (36 and 360 µg/kg IM or SC; 30 and 300 µg/kg IV) given as citrate solution in rats. Control groups receiving vehicle (saline) were run in parallel to monitor background plasma Al levels over time resulting from dietary intake.

Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products.

As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously re-evaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain.

Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications.

Results of an international transferability study of the BINACLE (binding and cleavage) assay for in vitro detection of tetanus toxicity.

Tetanus vaccines contain detoxified tetanus neurotoxin. In order to check for residual toxicity, the detoxified material (toxoid) has to be tested in guinea pigs. These tests are time-consuming and raise animal welfare issues.

Binding and cleavage (BINACLE) assay for the functional in vitro detection of tetanus toxin: applicability as alternative method for the safety testing of tetanus toxoids during vaccine production.

Tetanus toxoids (i.e. chemically inactivated preparations of tetanus neurotoxin) are used for the production of tetanus vaccines.

A multi-dose serological assay suitable to quantify the potency of inactivated rabies vaccines for veterinary use.

The mouse vaccination-challenge test, which is the most widely used method for determining the potency of inactivated rabies vaccines, is imprecise, time-consuming, and causes severe distress to the test animals. An alternative single-dose serological method has been implemented in the European Pharmacopoeia Monograph 0451 to replace the mouse challenge test for batch release. This single-dose limit method provides semi-quantitative results, but is not suitable for quantifying potency.