European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

© American Association of Pharmaceutical Scientists 2016, published by Springer US, available online at doi: https://doi.org/10.1208/s12249-016-0584-1The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.Peer reviewedFinal Accepted Versio

Vascular normalization: a real benefit?

International audienceIt is well established that antibodies to vascular endothelial growth factor (VEGF) in combination with chemotherapeutic agents produce synergistic cytotoxicity in a range of cancer. In this review article, it has been analyzed whether the so-called vascular normalization of abnormal tumor blood vessels as an effect of VEGF inhibition in association with chemotherapeutic agents in the treatment of tumors produces a real benefit. Literature data show that the process of normalization of the structure of tumor blood vessels is not always accompanied with a real benefit. In fact as in the case of cerebral tumors, the process of normalization may induce a re-establishment of the low permeability characteristics of normal brain microvasculature, preventing the delivery of chemotherapeutics

Characterisation of the Wildlife Reservoir Community for Human and Animal Trypanosomiasis in the Luangwa Valley, Zambia

Animal and human trypanosomiasis are constraints to both animal and human health in Sub-Saharan Africa, but there is little recent evidence as to how these parasites circulate in natural hosts in natural ecosystems. A cross-sectional survey of trypanosome prevalence in 418 wildlife hosts was conducted in the Luangwa Valley, Zambia, from 2005 to 2007. The overall prevalence in all species was 13.9%. Infection was significantly more likely to be detected in waterbuck, lion, greater kudu and bushbuck, with a clear pattern apparent of the most important hosts for each trypanosome species. Human infective Trypanosoma brucei rhodesiense parasites were identified for the first time in African buffalo and T. brucei s.l. in leopard. Variation in infection is demonstrated at species level rather than at family or sub-family level. A number of significant risk factors are shown to interact to influence infection rates in wildlife including taxonomy, habitat and blood meal preference. Trypanosoma parasites circulate within a wide and diverse host community in this bio-diverse ecosystem. Consistent land use patterns over the last century have resulted in epidemiological stability, but this may be threatened by the recent influx of people and domesticated livestock into the mid-Luangwa Valley

Anesthetic action on the transmission delay between cortex and thalamus explains the beta-buzz observed under propofol anesthesia

In recent years, more and more surgeries under general anesthesia have been performed with the assistance of electroencephalogram (EEG) monitors. An increase in anesthetic concentration leads to characteristic changes in the power spectra of the EEG. Although tracking the anesthetic-induced changes in EEG rhythms can be employed to estimate the depth of anesthesia, their precise underlying mechanisms are still unknown. A prominent feature in the EEG of some patients is the emergence of a strong power peak in the β–frequency band, which moves to the α–frequency band while increasing the anesthetic concentration. This feature is called the beta-buzz. In the present study, we use a thalamo-cortical neural population feedback model to reproduce observed characteristic features in frontal EEG power obtained experimentally during propofol general anesthesia, such as this beta-buzz. First, we find that the spectral power peak in the α– and δ–frequency ranges depend on the decay rate constant of excitatory and inhibitory synapses, but the anesthetic action on synapses does not explain the beta-buzz. Moreover, considering the action of propofol on the transmission delay between cortex and thalamus, the model reveals that the beta-buzz may result from a prolongation of the transmission delay by increasing propofol concentration. A corresponding relationship between transmission delay and anesthetic blood concentration is derived. Finally, an analytical stability study demonstrates that increasing propofol concentration moves the systems resting state towards its stability threshold

Microglial activation and chronic neurodegeneration

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype

Application of Microarray and Functional-Based Screening Methods for the Detection of Antimicrobial Resistance Genes in the Microbiomes of Healthy Humans

The aim of this study was to screen for the presence of antimicrobial resistance genes within the saliva and faecal microbiomes of healthy adult human volunteers from five European countries. Two non-culture based approaches were employed to obviate potential bias associated with difficult to culture members of the microbiota. In a gene target-based approach, a microarray was employed to screen for the presence of over 70 clinically important resistance genes in the saliva and faecal microbiomes. A total of 14 different resistance genes were detected encoding resistances to six antibiotic classes (aminoglycosides, β-lactams, macrolides, sulphonamides, tetracyclines and trimethoprim). The most commonly detected genes were erm(B), blaTEM, and sul2. In a functional-based approach, DNA prepared from pooled saliva samples was cloned into Escherichia coli and screened for expression of resistance to ampicillin or sulphonamide, two of the most common resistances found by array. The functional ampicillin resistance screen recovered genes encoding components of a predicted AcrRAB efflux pump. In the functional sulphonamide resistance screen, folP genes were recovered encoding mutant dihydropteroate synthase, the target of sulphonamide action. The genes recovered from the functional screens were from the chromosomes of commensal species that are opportunistically pathogenic and capable of exchanging DNA with related pathogenic species. Genes identified by microarray were not recovered in the activity-based screen, indicating that these two methods can be complementary in facilitating the identification of a range of resistance mechanisms present within the human microbiome. It also provides further evidence of the diverse reservoir of resistance mechanisms present in bacterial populations in the human gut and saliva. In future the methods described in this study can be used to monitor changes in the resistome in response to antibiotic therapy

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions