Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product. An important regulatory hurdle appeared to be the appropriate regulatory classification of the nTRACK nano-imaging agent, as neither the definition for medicinal product nor the definition for medical device appeared to be a good fit for the purpose of the product and we were confronted with diverging views of competent authorities on the classification. As a consequence, the information requirements to fulfill before conducting a First in Human trial are not evident and can only be decided upon by closely collaborating and communicating with the relevant authorities throughout the development of the product. Moreover, standard test methods for demonstrating the quality and safety of a medicinal product or medical device are not always suitable for nanomaterials such as the nTRACK nano-imaging agent. Regulatory agility is therefore a great need to prevent delay of promising medical innovations, although regulatory guidance on these products will likely improve with more experience. In this article, we outline the lessons learnt related to the regulatory process of the nTRACK nano-imaging agent for tracking therapeutic cells and offer recommendations to both regulators and developers of similar products.

Net carbon balance study for selected roads in Tenerife, Canary Islands.

Carbon dioxide emissions linked to the transport sector are particularly relevant to islands. The Canary Islands have high level of tourism, with tourists who generally travel in rented vehicles on arrival in the archipelago. In addition, mobility of the local population in the islands is also always growing. Thus, transport is one of the sectors that emits the greatest amount of greenhouse gases. In this sense, the net carbon balance becomes a pioneering study in the framework of management of high-capacity road transport routes and will help plan new strategies, which pursue the neutrality and climate resilience of the road network. It will therefore be possible to design different future scenarios, according to traffic intensities detected, to mitigate their local effects by increasing green areas, which will contribute to greater absorption. This study calculated the carbon footprint linked to vehicles on the three high-capacity roads on the island of Tenerife, as well as the carbon footprint of the public lighting attached to these roads. The absorption of carbon by vegetation planted by the Road Service and the soil located on the margins of the road have also been calculated to explore the possibility of modifying the vegetation, using other types of local shrubs and trees that have a higher absorption factor. The results demonstrate that conifers have the highest absorption factor, the Canary Island pine being the best option in this case. However, it is not always possible to place trees on the roadside, and it is necessary to resort to smaller species. This study concludes that better mobility planning, an increase in electric vehicles, improved energy production from renewable sources, and the promotion and enhancement of absorption capacity of carbon sinks are key in the face of climate change. Integr Environ Assess Manag 2023;19:1023-1030. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Lipid nanoparticles for alkyl lysophospholipid edelfosine encapsulation: development and in vitro characterization.

The ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, edelfosine (ET-18-OCH(3)) is the prototype molecule of a promising class of antitumor drugs named alkyl-lysophospholipid analogues (ALPs) or antitumor ether lipids. This drug presents a very important drawback as can be the dose dependent haemolysis when administered intravenously. Lipid nanoparticles have been lately proposed for different drug encapsulation as an alternative to other controlled release delivery systems, such as liposomes or polymeric nanoparticles. The aim of this study was to develop a lipid nanoparticulate system that would decrease systemic toxicity as well as improve the therapeutic potential of the drug. Lipids employed were Compritol 888 ATO and stearic acid. The nanoparticles were characterized by photon correlation spectroscopy for size and size distribution, and atomic force microscopy (AFM) was used for the determination of morphological properties. By both differential scanning calorimetry (DSC) and X-ray diffractometry, crystalline behaviour of lipids and drug was assessed. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by HPLC-MS. It was concluded that Compritol presents advantages as a matrix material for the manufacture of the nanoparticles and for the controlled release of edelfosine.

Productive trapping of NAD-type radicals. Non-biomimetic reduction of pyridinium salts.

One-electron reduction of pyridinium salts (NAD+ analogues) generates dihydropyridyl radicals which may then be engaged in radical addition processes to regioselectively form gamma-substituted dihydropyridines.

Hidatidosis del omóplato con localización extraósea / Scapular hydatidosis with extraosseous involvement

A forty three-year-old female, born in a rural area of southern Chile, at the age of 30 presented pain and limitation of motility of the righ shoulder. Later on, she presented an increasing of volume at the right scapular region. A radiography showed an osteolytic lesion of the scapula. In a biopsy an osseous hydatidosis was found and a hydatid cyst was extirpated from the soft tissues. Four years later, as she presented again pain and volume increasing in the same anatomical area, albendazole was given to her, and a CAT practiced revealed osteolytic lesions of the bone, several periosteal ruptures and multiple cyst in the muscles. She was submitted so surgery again in order to extirpate cyst. After two years the patient presented the same clinical manifestations and radiological and CAT images previously observed. In considering all these facts a radical surgery was decided

Seguimiento prolongado de pacientes con enfermedad hepática crónica por VHC / Long term follow up of patients with chronic hepatitis by CHV

Thirty two patients (18 males whose ages ranged from 32 to 68 years old) with hepatitis C virus chronic hepatitis (positive anti-HCV by ELISA, conformed by RIBA II) that were followed by the authors during 2 to 25 years, were retrospectively analyzed. 13 subjects had a history of blood transfusions, one had an accidental pinprick and other sexual contact with a HCV positive individual; the transmission source was not identified in the resting 19 subjects. Only 5 individuals had an acute onset. The rest of the patients had a few symptoms with moderate and fluctuating transaminase elevations. Liver biopsy at the onset showed a chronic hepatitis with moderate activity, even in 15 individuals with cirrhosis (47 percent). During follow up, six subjects deteriorated clinically, appearing liver failure and 3 of these died 4, 5 and 14 years after the disease appearance. No subject developed a hepatocarcinoma

Infección con el virus de la hepatitis E en Chile: comunicación preliminar / Hepatitis E virus infection in Chile: preliminary report

Using and Elisa technique, IgG antibodies against hepatitis E virus were measured in 40 alcoholics, 40 hemophilics, 174 blood donors, 36 subjects with acute non A non B non C hepatitis and 66 subjects with acute hepatitis A. Antibodies were detected in 1 alcoholic (2,5 percent), 3 hemophilics (7,5 percent), 7 blood donors (4 percent), 3 patients with non-A-non-B-non-C hepatitis (8,3 percent) and 3 patients with acute hepatitis A (4,5 percent). A low frequency of hepatitis E infection was detected in the studied subjects