Bioequivalence of narrow therapeutic index drugs and immunosuppressives

Stricter bioequivalence criteria are in place for generics where there are narrow therapeutic indexes such as generic immunosuppressives, enhancing their acceptance despite limited published studies. No serious issues have been reported to date with generic ciclosporine despite being on the market in Europe for more than 10 year

Beneficial or hazardous? A comprehensive study of 24 elements from wild edible plants from Angola

Angola suffers from a high child mortality rate and a prevalence of anemia due to malnutrition. The aim of this study is to provide a comprehensive overview of the mineral content of 43 wild edible plants. A total of 24 different elements (aluminum, antimony, arsenic, cadmium, calcium, chromium, cobalt, copper, iron, lead, lithium, magnesium, manganese, molybdenum, nickel, potassium, selenium, silicon, sodium, strontium, titanium, thallium, vanadium, zinc) were analyzed by inductively coupled plasma atomic emission spectroscopy to identify nutritional beneficial and hazardous plants. For the majority of studied species (31 of 43) data lack completely. For the remaining, only macronutrient contents are published yet, determining their (ultra)trace element and heavy metal contents for the first time. None of the examined plants pose a risk to human health due to low heavy metal contents, seasonality, and low amounts of consumed plant parts. Iron and zinc rich plant parts, such as fruits of Canarium schweinfurthii, or leaves of Crassocephalum rubens, Solanum americanum, and Piper umbellatum could help combating deficiency syndromes. The genus Landolphia shows to be an aluminum hyperaccumulator with aluminum contents >1000 mg/kg. Results of this study serve as a database for upcoming research. The nutritional value of edible plants is evaluated

Zukünftige Medienästhetik

Prof. Dr. Jens Schröter, Dr. Pablo Abend und Prof. Dr. Benjamin Beil sind Herausgeber der Reihe. Die Herausgeber*innen der einzelnen Hefte sind renommierte Wissenschaftler*innen aus dem In- und Ausland.Die ab Heft 1/2015 von Prof. Dr. Jens Schröter als Hauptherausgeber zusammen mit dem Graduiertenkolleg Locating Media (Universität Siegen) und Prof. Dr. Benjamin Beil (Universität zu Köln) herausgegebene kultur- und medienwissenschaftliche Zeitschrift Navigationen widmet sich in ihrer aktuellen Ausgabe (2/2021) dem Thema Zukünftige Medienästhetik. Eine zukünftige Medienästhetik ist sowohl eine Medienästhetik der Zukunft, als auch eine Ästhetik zukünftiger Medien. Medienkunst hat schon immer ungedachte und unversuchte Möglichkeiten verschiedenster Medien ausprobiert und damit einen imaginativen Vorschein zukünftiger Medien erzeugt. Medienkunst, eine der zentralen Kunstformen des 20. und 21. Jhds., sah es als eine ihrer Aufgaben an, neue Medien zu erfinden (Rosalind Krauss) – oft gerade im Rückgriff auf obsolet wirkende Technologien und Verfahren. Medienkunst reflektiert also nicht bloß ein zugrundeliegendes Medium, wie es von der (hoch-)modernistischen Ästhetik und problematisch genug, für alle Kunst behauptet wurde. Sie erfindet erst ein Medium. Medien sind dabei von Imaginationen umgeben, die ihrer Erfindung vorhergehen, ihre Durchsetzung begleitet und in ihrem Verschwinden nostalgisch nachklingen. Medienkunst kann deshalb als ein spezieller Fall solcher Imaginationen verstanden werden – eine Imagination, die nicht (nur) diskursiv, sondern materiell, demonstrativ und performativ aufgeführt wird. In dem geplanten Heft sind Beiträge versammelt, die die Praktiken der Erfindung zukünftiger Medien durch die Medienkunst untersuchen. Ein Schwerpunkt liegt dabei auf dem wichtigen medienkünstlerischen Projekt Piazza virtuale von Van Gogh TV, welches auf der documenta IX 1992, genau am Vorabend der Ausbreitung des Internets, das zukünftige Medium eines interaktiven Fernsehens entwarf.A future media aesthetic is both a media aesthetic of the future and an aesthetic of future media. Media art has always explored unimagined and untried possibilities of various media, creating an imaginative glimpse of future media. Media art, one of the central art forms of the 20th and 21st centuries, saw it as one of its tasks to invent new media (Rosalind Krauss) - often precisely by resorting to technologies and processes that seem obsolete. Media art, then, does not merely reflect an underlying medium, as was claimed by (high) modernist aesthetics, and problematically enough, for all art. It first invents a medium. Media are thereby surrounded by imaginaries that precede their invention, accompany their enforcement, and resonate nostalgically in their disappearance. Media art can therefore be understood as a special case of such imaginaries - an imagination that is not (only) discursive, but material, demonstrative and performative. The planned issue gathers contributions that examine the practices of inventing future media through media art. One focus is on the important media art project Piazza virtuale by Van Gogh TV, which conceived the future medium of an interactive television at documenta IX in 1992, precisely on the eve of the spread of the Internet

Essential to increase the use of generics in Europe to maintain comprehensive health care?

INTRODUCTION: Reforms have been introduced across Europe to increase prescribing efficiency with existing drugs. These include measures to lower prices of generics as well as increase their prescribing versus originators and patented products in a class or related class. This is essential to maintain comprehensive health care in Europe given continued pressures. The alternative is insufficient funds for new innovative drugs and increasing drug volumes with ageing populations. OBJECTIVE: To review the influence of measures and initiatives to increase the prescribing and dispensing of generics at low prices on ambulatory care prescribing efficiency. In view of this, provide guidance as authorities strive to introduce further reforms to meet their goals. METHODOLOGY: A narrative review of published papers combined with case histories. RESULTS: The different supply- and demand-side measures have reduced generic prices to as low as 2% to 3% of pre-patent loss prices in some cases as well as appreciably enhanced their utilisation. As a result, prescribing efficiency has increased without compromising care. In some cases, the reforms have led to expenditure actually falling despite appreciably increased volumes. CONCLUSIONS: Increasing use of generics at low prices will help maintain the European ideals of comprehensive and equitable health care. However, countries will continually need to learn from each other

Initiatives to increase the prescribing of low cost generics : the case of Scotland in the international context

Getting the most out of the pharmaceutical budget is critical across all countries as the financial pressures on healthcare systems intensify. In this paper, we review global practice on encouraging the use of low costs generics versus branded pharmaceuticals, including patented products in the same class where care is not compromised across countries to guide future practice. Our review ranges widely across European countries as well as other high income countries, including Abu Dhabi, Japan and the USA, and other low and middle income Countries. There is a particular focus on Scotland, building on previous publications. We conclude based on multiple publications, including several case studies, that achieving efficiency in pharmaceutical spending is possible in virtually all environments, although there are examples of technologies where generic or therapeutic substitution should not be encouraged. However, there is no magic bullet to achieving full and appropriate use of generics. Countries have to be prepared to use a number of different education, economic, engineering and enforcement methods including prescribing restrictions to achieve success. Similarly, different approaches to achieve low prices for good quality generics given the considerable price differences that currently exist. The combination of low prices and increased use of generics will help achieve or attain universal healthcare, benefiting all key stakeholder groups. We conclude with a call for greater cross-country learning in pursuit of what should be a common goal for all health systems

Generic pregabalin : current situation and implications for health authorities, generics and biosimilars manufacturers in the future

The manufacturer of pregabalin has a second use patent covering prescribing for neuropathic pain: its principal indication. The manufacturer has threatened legal action in the UK if generic pregabalin rather than Lyrica is prescribed for this indication. No problems exist for practitioners who prescribe pregabalin for epilepsy or generalized anxiety disorder. This has serious implications for health authorities. In Germany, however, generics could be legally prescribed for any approved indication once one indication loses its patent. We aim to establish the current situation with pregabalin among principally European countries. Personnel from 33 regional and national health authorities mainly from Europe, and nine from universities across Europe working as advisers to health authorities or with insight into their activities, were surveyed regarding four specific questions via email to shed light on the current situation with Lyrica and pregabalin in their country. The information collated from each country was subsequently checked for accuracy with each co-author by email and face-to-face contact and collated into five tables. The scenarios ranged from extending the patent life of Lyrica (e.g. France), endorsing the prescribing of Lyrica for neuropathic pain (e.g. Catalonia and South Korea), and current prescribing of pregabablin for all indications (e.g. Serbia and Germany). Little activity has taken place in European countries in which generic pregabalin is not yet reimbursed. The availability of generic pregabalin has prompted a number of different activities to be undertaken among the 33 countries and regions surveyed. The situation in Serbia and the historic situation in Germany provide examples of ways to maximize savings once a product loses its patent for at least one indication

Why are self-medication opportunities limited in Austria? An interview study and comparison with other countries.

BackgroundAustria has high health resource use compared to similar countries. Reclassifying (switching) medicines from prescription to non-prescription can reduce pressure on health resources and aid timely access to medicines. Since Austria is less progressive in this area than many other countries, this research aimed to elucidate enablers and barriers to it reclassifying medicines and make recommendations for change in the context of similar research conducted elsewhere.MethodsQualitative research using a heuristic approach was conducted in Austria in 2018. Informed by their own "insider" and "outsider" knowledge, the authors identified themes from personal interviews with 24 participants, including reclassification committee members, government officials and stakeholders, before comparing these themes with earlier research findings.ResultsSignificant barriers to reclassification included committee conservatism, minimal political support, medical negativity and few company applications. Insufficient transparency about committee decisions, expectations of adverse committee decisions and a limited market discouraged company applications. Austria's 'social partnership' arrangement and consensus decision making aided a conservative approach, but the regulator and an alternative non-committee switch process were enabling. Pharmacy showed mixed interest in reclassification. Suggested improvements include increasing transparency, committee composition changes, encouraging a more evidence-based approach by the committee, more pharmacy undergraduate clinical training, and companies using scientific advisory meetings and submitting high quality applications.ConclusionRemoving barriers to reclassification would facilitate non-prescription availability of medicines and encourage self-care, and could reduce pressure on healthcare resources

Super-Resolution Imaging of ESCRT-Proteins at HIV-1 Assembly Sites

The cellular endosomal sorting complex required for transport (ESCRT) machinery is involved in membrane budding processes, such as multivesicular biogenesis and cytokinesis. In HIV-infected cells, HIV-1 hijacks the ESCRT machinery to drive HIV release. Early in the HIV-1 assembly process, the ESCRT-I protein Tsg101 and the ESCRT-related protein ALIX are recruited to the assembly site. Further downstream, components such as the ESCRT-III proteins CHMP4 and CHMP2 form transient membrane associated lattices, which are involved in virus-host membrane fission. Although various geometries of ESCRT-III assemblies could be observed, the actual membrane constriction and fission mechanism is not fully understood. Fission might be driven from inside the HIV-1 budding neck by narrowing the membranes from the outside by larger lattices surrounding the neck, or from within the bud. Here, we use super-resolution fluorescence microscopy to elucidate the size and structure of the ESCRT components Tsg101, ALIX, CHMP4B and CHMP2A during HIV-1 budding below the diffraction limit. To avoid the deleterious effects of using fusion proteins attached to ESCRT components, we performed measurements on the endogenous protein or, in the case of CHMP4B, constructs modified with the small HA tag. Due to the transient nature of the ESCRT interactions, the fraction of HIV-1 assembly sites with colocalizing ESCRT complexes was low (1.5%-3.4%). All colocalizing ESCRT clusters exhibited closed, circular structures with an average size (full-width at half-maximum) between 45 and 60 nm or a diameter (determined using a Ripley's L-function analysis) of roughly 60 to 100 nm. The size distributions for colocalizing clusters were narrower than for non-colocalizing clusters, and significantly smaller than the HIV-1 bud. Hence, our results support a membrane scission process driven by ESCRT protein assemblies inside a confined structure, such as the bud neck, rather than by large lattices around the neck or in the bud lumen. In the case of ALIX, a cloud of individual molecules surrounding the central clusters was often observed, which we attribute to ALIX molecules incorporated into the nascent HIV-1 Gag shell. Experiments performed using YFP-tagged Tsg101 led to an over 10-fold increase in ESCRT structures colocalizing with HIV-1 budding sites indicating an influence of the fusion protein tag on the function of the ESCRT protein

Metal Accumulation Properties of Eight Traditionally Utilized Nutritional Plants and Their Potential as Suitable Crops for Cultivation on Acidic Soils of the Northern Province Uíge, Angola

High metal contents of acidic soils from sub-Saharan Africa often prevent the cultivation of crops and lead to a low livestock yield. The carbohydrate rich diet of the Angolan population is low in minerals and vitamins, resulting in various deficiency syndromes and a high child mortality rate. Eight traditionally utilized plants (Anisophyllea quangensis, Annona stenophylla subsp. cuneata, Canarium schweinfurthii, Eugenia malangensis, Landolphia lanceolata, Raphionacme madiensis, Tristemma mauritianum, Vitex madiensis subsp. madiensis) with nutritional value for the Angolan population were analyzed for their soil and growing conditions. The species are adapted to the local conditions and can serve as crops for the unfavorable soils of the province Uíge. Chemical and physical characteristics of the uppermost soil (0–5 cm) and in 30 cm depth were analyzed. The plant-available macro-and micronutrients were determined using Mehlich 3 extraction. Data are completed with leaf tissue analyses, examining the uptake of minerals. As aluminum (Al) and manganese (Mn) are plant-available in high amounts, local plants evolved mechanisms dealing with those metals. These Al accumulators with foliar contents above 1000 mg/kg are Anisophyllea quangensis (7884 mg/kg), Landolphia lanceolata (6809 mg/kg), Tristemma mauritianum (4674 mg/kg), and Eugenia malangensis (13,989 mg/kg). All four species bear edible fruits with nutritional potential. The domestication and commercialization of those plants seem to be promising, utilizing local soils without expensive amelioration techniques