The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4′-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease

Technical limits of model accuracy

Shelf life prediction by intelligent RFI

Destruction de Rhizopus stolonifer et Botrytis cinerea par des traitements ozone/ions

L’activité fongicide des traitements ozone/ionisation a été étudiée. Rhizopus stolonifer et Botrytis cinerea, deux moisissures pathogènes communes de l’entreposage des fraises, ont été inoculées sur gélose et exposées à 106 ions/cm3 d’air et à des concentrations d’ozone de 0,05; 0,1; 0,5 et 1 ppm. En guise d’application, des fraises ont été inoculées par lésion avec chaque souche de moisissure et traitées aux mêmes concentrations d’ozone pour 12, 24, 48, 72 heures et comparées à un témoin inoculé non traité. Les résultats obtenus ont démontré un effet fongicide significatif et/ou fongistatique des traitements combinés ozone/ionisation sur les moisissures étudiées. Les expériences sur gélose ont montré que les teneurs en ozone de 0,05 et 0,1 ppm ont permis, après 36 heures de traitement, de réduire respectivement de 57 et 76 % les populations de R. stolonifer, et de 68 et 78 % les populations de B. cinerea. Pour les concentrations d’ozone de 0,5 et 1 ppm, une réduction de 99 % pour R. stolonifer et de 98 % pour B. cinerea a été observée. Sur les fraises exposées à 1 ppm d’ozone, après 72 heures de traitement, 91,1 et 98,8 % de réduction des populations de R. stolonifer et B. cinerea ont été observées respectivement.The fungicidal activity of the combined treatment ozone/ions was investigated on the development of Rhizopus stolonifer and Botrytis cinerea. R. stolonifer and B. cinerea, two common postharvest pathogens of strawberries, were inoculated on gelose and exposed to 106 ions/cm3 of air with ozone concentrations of 0.05, 0.1, 0.5 or 1 ppm. Strawberries were wounded and inoculated with R. stolonifer or B. cinerea and exposed to the same ozone/ions concentrations for 12, 24, 48 and 72 hours. The results showed a significant fungicidal and/or fungistatic effect of the combined ozone/ions treatments on the fungus. In vitro treatments showed that, after 36 hours of exposure to ozone concentrations of 0.05 and 0.1 ppm, the cell count decrease for R. stolonifer was 57 and 76% respectively, while it was 68 and 78% for B. cinerea. Exposure to ozone concentrations of 0.5 and 1 ppm over the same period of time resulted in 99 and 98% decrease for R. stolonifer and B. cinerea, respectively. Ozone/ions treatment in wounded strawberries allowed 91.1 and 98.8% reduction of the counts after 72 hours of exposure to 1 ppm of ozone respectively for R. stolonifer and B. cinerea

Blueberry supply chain: Critical steps impacting fruit quality and application of a boosted regression tree model to predict weight loss

Blueberries have increased in popularity in recent years due to their nutritional benefits and sensory characteristics. However, to preserve quality and extend shelf-life, they need to be maintained at refrigerated temperatures and high relative humidity, conditions that are not routinely met along the supply chain. Poor temperature management leads to quality deterioration, increasing waste/losses along the supply chain. This study examined the impact of each step along the supply chain on the physichochemical quality and shelf-life of blueberries, identifying the most critical steps from field to consumption. The following steps were identified as critical in the blueberry supply chain: shipping to distribution centre (DC) (72 h at 5 °C), store display (48 h at 15 °C), and consumer (48 h at 20 °C). Given the economic importance of weight loss and its link to fruit quality and shelf-life, a boosted regression tree (BRT) model was built to predict weight loss using the post-harvest environmental conditions of a simulated supply chain applying different temperature-time scenarios. The model explained 84 % of the variance on the test set and highlighted the interactions of supply chain conditions on weight loss.European Commission Horizon 2020US Department of Agriculture (USDA

New Efficient Recombinant Expression System To Engineer Candida antarctica Lipase B▿ †

Here, we report the use of Yarrowia lipolytica as a versatile expression host for developing protein engineering approaches to modify the properties of Candida antarctica lipase B. A reliable screening protocol was defined and validated using a saturation mutagenesis library, yielding mutants displaying higher catalytic efficiencies than the wild-type enzyme

Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism

International audienceBackground and aims: Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty years. Its potentiation effect on hepatotoxic agents has been demonstrated in animal models. We investigated the relationship between environmental exposure to chlordecone and the progression of liver fibrosis.Methods: This study included 182 consecutive patients with chronic alcoholic hepatitis whose liver fibrosis was assessed using non-invasive methods. Measured plasma chlordecone concentrations at inclusion were used as surrogate of long-term exposure under steady-state conditions. As the pharmacokinetic processing of chlordecone is largely determined by the liver, we used a human physiologically based pharmacokinetic model to predict plausible changes in the steady-state blood chlordecone concentrations induced by liver fibrosis.Results: With a median follow-up of 27.1 years after the onset of alcohol consumption, we found a significant decrease in the risk of advanced liver fibrosis with increasing plasma chlordecone concentration (adjusted hazard ratio = 0.56; 95% confidence interval: 0.34-0.95 for the highest vs. lowest tertile, p = 0.04). Changes induced by liver fibrosis influenced the pharmacokinetic processing of chlordecone, resulting in substantial modifications in its steady-state blood concentrations.Conclusion: According to this human model of coexposure to alcohol, reverse causality is the most plausible explanation of this inverse association between plasma chlordecone concentrations and progression of liver fibrosis. This study underlines the importance of considering the pharmacokinetic of environmental contaminants in epidemiological studies when biomarkers of exposure are used to investigate their own impact on the liver.Trial registration: ClinicalTrials.gov Identifier: NCT03373396