A non-invasive, sensor-based approach to exploit the autofluorescence of saffron (Crocus sativus L.) for on-site evaluation of aging.

So far, compliance with ISO 3632 standard specifications for top-quality saffron guarantees good agricultural and post-harvest production practices. Tracking early-stage oxidation remains challenging. Our study aims to address this issue by exploring the visible, fluorescence, and near-infrared spectra of category I saffron. Using a multi-spectral sensor, we tested fresh and artificially aged saffron in powder form. High autofluorescence intensities at 600-700 nm allowed calibration for the 'content of aged saffron'. Samples with minimum coloring strength (200-220 units) were classified as 70% aged, while those exceeding maximum aroma strength (50 units) as 100% aged. Consistent patterns across origin, age, and processing history indicated potential for objectively assessing early-oxidation markers. Further analyses uncovered multiple contributing fluorophores, including cis-apocarotenoids, correlated with FTIR-based aging markers. Our findings underscore that sensing autofluorescence of traded saffron presents an innovative quality diagnostic approach, paving new research pathways for assessing the remaining shelf-life along its supply chain.

Discovering the hidden messages within cell trajectories using a deep learning approach for in vitro evaluation of cancer drug treatments.

We describe a novel method to achieve a universal, massive, and fully automated analysis of cell motility behaviours, starting from time-lapse microscopy images. The approach was inspired by the recent successes in application of machine learning for style recognition in paintings and artistic style transfer. The originality of the method relies i) on the generation of atlas from the collection of single-cell trajectories in order to visually encode the multiple descriptors of cell motility, and ii) on the application of pre-trained Deep Learning Convolutional Neural Network architecture in order to extract relevant features to be used for classification tasks from this visual atlas. Validation tests were conducted on two different cell motility scenarios: 1) a 3D biomimetic gels of immune cells, co-cultured with breast cancer cells in organ-on-chip devices, upon treatment with an immunotherapy drug; 2) Petri dishes of clustered prostate cancer cells, upon treatment with a chemotherapy drug. For each scenario, single-cell trajectories are very accurately classified according to the presence or not of the drugs. This original approach demonstrates the existence of universal features in cell motility (a so called "motility style") which are identified by the DL approach in the rationale of discovering the unknown message in cell trajectories.

Multifunctional magnetic nanoparticles for enhanced intracellular drug transport.

In this paper we report the synthesis and characterization of biocompatible multi-functional magnetic nanoparticles (MNPs) able to enhance the intracellular transport of N-methylated drugs. The Fe3O4 magnetic core was first functionalized with a mixed monolayer consisting of two different phosphonic acids having terminal acetylenic and amino groups, which provide an active platform for further functionalization with organic molecules. Then, a tetraphosphonate cavitand receptor (Tiiii) bearing an azide moiety and the N-hydroxysuccinimide (NHS) activated forms of poly(ethylene glycol) (PEG), folic acid (FA) and carboxy-X-rhodamine (Rhod) were covalently anchored on alkyne and amine moieties respectively, through 1,3-dipolar cycloaddition and EDC/NHS coupling reactions. The obtained MNPs are biocompatible and possess magnetic, luminescence and recognition properties which make them suitable for multimodal theranostic applications. In particular, combined confocal microscopy and cytotoxicity experiments showed that these multi-functional MNPs are able to recognize a specific drug "in situ" and promote its cellular internalization, thus enhancing its efficiency.

Nitric oxide production by macrophages of dogs vaccinated with killed Leishmania infantum promastigotes.

Human visceral leishmaniosis is endemic in Southern Italy, where the dog is the main reservoir of viscerotropic strains of Leishmania infantum. The release of nitric oxide (NO) by interferon (IFN)-gamma-activated macrophages is an important leishmanicidal mechanism in several animal species. In this work NO production, phagocytosis and killing capacity of monocyte-derived dog macrophages were evaluated in vitro before and after administration of a vaccine composed of killed Leishmania infantum promastigotes. Moreover, IFN-gamma content was measured in concanavalin A-activated dog peripheral blood mononuclear cell (PBMC) supernatants employed for macrophage stimulation. Phagocytosis, killing capacity and NO production by canine macrophages increased significantly 1 month after vaccine administration, and the increase also persisted 5 months later. In addition, the amount of IFN-gamma in PBMC supernatants was significantly higher after vaccination. Overall, our results suggest the usefulness of evaluating the in vivo protective role of this promastigote preparation in dogs.

Pharmacokinetics and tissue distribution of iomeprol in animals.

The pharmacokinetics of iomeprol, a new triiodinated nonionic radiographic contrast agent, has been studied in rats, rabbits and dogs. Following intravenous administration, iomeprol did not bind measurably to plasma proteins and was rapidly excreted in unchanged form, mostly through the kidneys. The compound was rapidly distributed to the plasma and thence to the extracellular spaces. Iomeprol did not accumulate in specific organs or tissues except for those involved in its elimination, i.e. the kidneys and the liver. However, 24 h after administration, less than 1% of the injected dose remained in the tissues. The overall profile was very similar to the published profiles of other radiographic contrast agents used in uroangiography.

Preclinical safety assessment of iomeprol for injection as contrast medium for myelography.

A series of pharmaco-toxicological investigations were carried out in animals in order to assess the neurotolerance of iomeprol, a new nonionic iodinated contrast medium. After intrathecal administration iomeprol was completely eliminated from the cerebrospinal fluid, rapidly cleared from the plasma and excreted unchanged through the kidneys. When administrated intrathecally, iomeprol did not significantly alter the behavioural functions or the physiological activities of the brain. Unlike other contrast media, iomeprol was devoid of any epileptogenic activity. The acute neurotoxicity of iomeprol was comparable with that of iopamidol, but less than that of iohexol, iotrolan and iodixanol. Iomeprol was well tolerated in both rats and dogs following weekly intrathecal administrations for four weeks of doses up to three times higher than those foreseen for clinical use. High neurotolerance in animals and favourable physico-chemical characteristics make iomeprol particularly suitable as a contrast medium for both myelography and cerebral ventriculography.

Functionalization of PEGylated Fe3O4 magnetic nanoparticles with tetraphosphonate cavitand for biomedical application.

In this contribution, Fe3O4 magnetic nanoparticles (MNPs) have been functionalized with a tetraphosphonate cavitand receptor (Tiiii), capable of complexing N-monomethylated species with high selectivity, and polyethylene glycol (PEG) via click-chemistry. The grafting process is based on MNP pre-functionalization with a bifunctional phosphonic linker, 10-undecynylphosphonic acid, anchored on an iron surface through the phosphonic group. The Tiiii cavitand and the PEG modified with azide moieties have then been bonded to the resulting alkyne-functionalized MNPs through a "click" reaction. Each reaction step has been monitored by using X-ray photoelectron and FTIR spectroscopies. PEG and Tiiii functionalized MNPs have been able to load N-methyl ammonium salts such as the antitumor drug procarbazine hydrochloride and the neurotransmitter epinephrine hydrochloride and release them as free bases. In addition, the introduction of PEG moieties promoted biocompatibility of functionalized MNPs, thus allowing their use in biological environments.

High-performance liquid chromatographic assay of the X-ray contrast agent iopiperidol in plasma and urine of rats and humans.

Iopiperidol is a non ionic iodinated compound currently under evaluation as a potential contrast medium with anticoagulant property for radiological examinations. An HPLC method for assaying iopiperidol in plasma and urine of rats and humans is described. The analysis is based on the reversed-phase chromatographic separation of iopiperidol and the internal standard (iopamidol) from the endogenous components of the biological fluids, and their detection by UV absorption at 244 nm. The selectivity of the method was satisfactory. The mean absolute recovery was greater than 80%. The precision and accuracy of the analytical methods were in the range 0.3 to 3.3 and -8.5 to +11%, respectively. The detection limits of iopiperidol in plasma (0.1 ml) and urine (0.25 ml) were 0.2 and 0.4 microg/ml, respectively.

High-performance liquid chromatographic determination of the X-ray imaging contrast agent, iofratol, in plasma and urine.

Iofratol is currently under evaluation as a potential X-ray contrast medium for angiography and myelography. An HPLC method for assaying iofratol in rat and human plasma and urine samples is described. The analysis is based on the reversed-phase chromatographic separation of iofratol and the internal standard (iopamidol) from the endogenous components of biological fluids, and detection by UV absorption at 242 nm. The selectivity of the method was satisfactory. The mean absolute recovery was greater than 90%. The precision and accuracy of the analytical methods were in the range 0.8-7.4 and -7.8 to +9.7%, respectively. The detection limits in plasma (0.1 ml) and urine (0.5 ml) were 0.1 and 0.4 microg (iofratol)/ml, respectively. The analyte was stable in the different biological matrices when stored at room temperature (20 degrees C) for at least 1 day, 4 degrees C for 1 month and -20 degrees C for 1 year.

High-performance liquid chromatographic determination of the magnetic resonance imaging contrast agent gadobenate ion in plasma, urine, faeces, bile and tissues.

The gadobenate ion is an intravascular paramagnetic contrast agent for magnetic resonance imaging. An HPLC method for assaying gadobenate ion in plasma, urine, faeces, bile and tissue samples is described. The analysis is based on the reversed-phase chromatographic separation of gadobenate ion from the endogenous components of biological matrices and detection by UV absorption at 210 nm. The selectivity of the method was satisfactory. The mean absolute recovery was greater than 95%. The precision and accuracy of the analytical methods were in the range 0.1-6.5% and -12 to +9.3%, respectively. The detection limits in plasma (0.1 ml), urine (0.05 ml), dried faeces (200 mg suspended in 4 ml water), bile (0.5 ml), and dried liver tissue (100 mg suspended in 1 ml water) were, respectively, 0.24, 0.47, 2.6, 0.63 and 2.8 nmol ml(-1) (corresponding to 0.16, 0.31, 1.7, 0.42 and 1.9 microg ml(-1)).

Conditioned taste aversion in rats following intrathecal administration of contrast media.

PURPOSE: The occurrence of side-effects such as visceral malaise after intrathecal administration of the non-ionic radiography contrast media iomeprol, iopamidol, and iotrolan was assessed in rats by the conditioned tasted aversion procedure. METHODS: Reduced preference towards a saccharose solution compared with normal water following intraventricular administration of a contrast medium was used as a measure of the aversive response. RESULTS: At a dose of 100 mg I/kg none of the tested contrast media induced aversion. At 200 and 300 mg I/kg, both iopamidol and iomeprol induced significant aversive responses with respect to control, although the response of the iomeprol group appeared milder than that of the iopamidol group at a dose of 200 mg I/kg. Iotrolan could be tested only at the lowest dose since the high doses caused excessive mortality. CONCLUSION: Intrathecally administered iomeprol appeared to be well tolerated in rats at doses higher than those suggested for clinical use.