Real-Time Phase-Contrast MRI to Monitor Cervical Blood and Cerebrospinal Fluid Flow Beat-by-Beat Variability

Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The arterial (AF), venous (VF), and cerebrospinal fluid (CSF) flow (CSFF) were computed as velocity integrals over the internal carotid artery, internal jugular vein, and CSF. AF, VF, and CSFF signals were segmented in inspiration and expiration beats, to assess the respiration influence. Systolic and diastolic BBV, and heart period series underwent autoregressive power spectral density analysis, to evaluate the low-frequency (LF, Mayer waves) and high frequency (HF, respiratory waves) components. The diastolic VF had the largest BBV. LF power was high in the diastolic AF series, poor in all CSFF series. The pulse wave analyses revealed higher mean amplitude during inspiration. Findings suggests a possible role of LF modulation of IC resistances and propagation of HF waves from VF to AF and CCSF. PC-RT-MRI could provide new insight into the interaction between CV and IC regulation and pave the way for a detailed analysis of the cerebrovascular effects of varied respiration patterns due to exercise and rehabilitation

Environmental photochemistry of fluoroquinolones in soil and in aqueous soil suspensions under solar light

The photodegradation fate of widely used fluoroquinolone (FQ) drugs has been studied both at the water–soil interface and in soil at actual concentrations (500 ng g−1) under natural solar light. Both human and veterinary drugs have been examined, namely ciprofloxacin, danofloxacin, enrofloxacin, levofloxacin, marbofloxacin and moxifloxacin. After spiking and irradiation, samples were submitted to microwave-assisted extraction and analyzed by high-performance liquid chromatography coupled to fluorescence detection (HPLC–FD). FQs degradation was faster in aqueous soil suspension than in neat soil (but lower than in “clean” water). A number of byproducts were identified by HPLC electrospray ionization tandem mass spectrometry after a post-extraction cleanup based on a molecularly imprinted polymer phase, for a more accurate detection. The distribution in the suspension was intermediate between those observed in soils and in aqueous solutions

Photochemical degradation of Marbofloxacin and Enrofloxacin in natural waters

The photochemical fate of Marbofloxacin (MAR) and Enrofloxacin (ENR), two Fluoroquinolones (FQs) largely used as veterinary bactericides known to be present in surface waters, was investigated in aqueous solution. The degradation of these pollutants (5-50 μg/L starting concentration) was complete in about 1 h by exposure to solar light (summer) and obeyed a first-order kinetics. The structure of the primary photoproducts was determined. Those from ENR arose through three paths, namely, oxidative degradation of the piperazine sidechain, reductive defluorination, and fluorine solvolysis. More heavily degraded products that had been previously reported were rationalized as secondary photoproducts from the present ones. As for MAR, this underwent homolytic cleavage of the tetrahydrooxadiazine moiety to give two quinolinols. All of the primary products were themselves degraded in about 1 h. The photoreactions rates were scarcely affected by Ca2+ (200 mg/L), Mg2+ (30 mg/L), Cl- (30 mg/L), and humic acid (1 mg/L), but increased in the presence of phosphate (20 mg/L). The fastest degradation of ENR occurred at pH about 8 where the zwitterionic form was present, while in the case of MAR the cationic form was the most reactive

Environmental photochemistry of Fluoroquinolones in soil and in aqueous soil suspensions under natural solar light

1. Introduction Fluoroquinolones (FQs) are a family of synthetic, broad-spectrum antibiotics as human and veterinary drugs. FQs are metabolized only in small part, therefore a large fraction of the ingested dose is excreted unmodified and reaches environmental waters in the pharmaceutically active form. These compounds rapidly move to solid matrices, i.e. sediments and soil, due to the high distribution coefficients [1], and eventually undergo photodegradation. Degradation rates and, consequently, persistence depend on the ambient conditions. Photochemical processes are largely affected by matrix composition, i.e. on the physical state of the drug (in solution or adsorbed on soil particles), on light power and on the role of inorganics and natural organic matter acting as photosensitizers [2-4]. FQs are emerging contaminants that have been detected worldwide in natural waters [5] and soils [6] at concentrations at the ppb level and below. With the aim to explore the FQ environmental fate in such matrices, we have studied their photodegradation in natural water [6-8] and in sunlight-exposed soil [9]. Photochemistry plays a major role in the environmental fate of FQ pharmaceuticals, and the study of the resulting photoproducts is of great importance in order to avoid underestimating the FQ environmental impact [8, 10, 11]. 2. Results The photodegradation fate of widely used Fluoroquinolones (FQs) in solid environmental matrices has been studied at actual concentrations (500 ng g-1) under natural solar light. Both human and veterinary drugs have been chosen, namely Ciprofloxacin (CIP), Danofloxacin (DAN), Enrofloxacin (ENR), Levofloxacin (LEV), Marbofloxacin (MAR) and Moxifloxacin (MOX). In this work, the photochemical behaviour of adsorbed FQs at the water-soil interface was investigated for the first time, in view of the great relevance to natural ecosystems and compared to their photodegradation in sunlit soil. After spiking and irradiation, samples were submitted to microwave-assisted extraction and analyzed by high performance liquid chromatography coupled to fluorescence detection (HPLC-FD). The photochemical fate of the parent compound and the time evolution of byproducts was monitored at the ppb levels by HPLC-FD. This proved that FQs are degraded considerably in these matrices. The degradation rates measured in aqueous soil suspension were higher than in neat soil, but lower than in water solution. A number of different byproducts, identified by HPLC electrospray ionization tandem mass spectrometry ESI-MS/MS after a post-extraction cleanup based on a molecularly imprinted polymer-phase, were formed during the photolytic process. The analysis of the photoproducts shows that on solid matrix (viz. FQs adsorbed on soils) the main photoprocess is the oxidative degradation started from the most labile moiety, the amine side-chain. On the contrary, the two main photodegradative paths observed in solution for this class of molecules, viz. dehalogenation and photosubstitution, are absent or remain only as secondary processes in the case of the less reactive FQs (LEV, MOX). The long time required for the photodegradation and the low reactivity make the two latter paths competitive with degradative oxidation, which however remains the predominant path. When a borderline situation is explored, viz. aqueous soil suspensions, our results suggest that the primary photochemical processes are due to soil adsorbed rather than to water dissolved molecules, further underling the strong interaction of FQs with the soil matrix. 3. Conclusions We have explored the environmental photochemistry of six widely used FQs in two important matrices, specifically agricultural soil and aqueous soil suspension, the latter not previously studied. Natural solar light proved to degrade consistently such drugs (nanograms per gram level), with higher degradation rates found in aqueous soil suspension than in neat soil. In particular, among the FQs studied, LEV and MOX were the two more persistent drugs. The results we obtained indicate that the persistence of these antibiotic compounds is longer in such matrices than in surface water, that is in soil > aqueous soil suspension > water

Sunlight-induced degradation of soil-adsorbed veterinary antimicrobials Marbofloxacin and Enrofloxacin

Marbofloxacin (MAR) and Enrofloxacin (ENR), two largely employed veterinary Fluoroquinolones (FQs), were found to be present at the micrograms per kilogram level in agricultural soils of South Lombardy (Italy) several months after manuring. Distribution coefficients (Kd) from sorption experiments indicated a strong binding to the soil. Soil samples fortified with environmentally significant FQs amounts (0.5 mg/kg) were exposed to solar light that promoted extensive degradation (80%) of both drugs in 60–150 h. Thus, photochemistry could be considered a significant depollution path in the soil, although it was two orders of magnitudes slower than in aqueous solution and a fraction of the drug (ca. 20%) remained unaffected. For MAR the photoprocess was the same as in solution, and involved cleavage of the tetrahydrooxadiazine ring. On the contrary, with ENR only some of the photoproducts determined in water (those arising from a stepwise oxidation of the piperazine side chain) were observed. Substitution of the 6-fluoro by a hydroxyl group and reduction did not occur in the soil, supporting the previous contention that such processes required polar solvation of FQs. Consistently with this rationalization, the irradiation of thin layers of solid drugs led to essentially the same products distribution as in the soil. From the environmental point of view it is important to notice that photodegradation mainly affects the side-chains, while the fluoroquinolone ring, to which the biological effect is associated, is conserved up to the later stages of the degradation

The Tomato Metallocarboxypeptidase Inhibitor I, which Interacts with a Heavy Metal-Associated Isoprenylated Protein, Is Implicated in Plant Response to Cadmium

Metallocarboxypeptidases are metal-dependent enzymes, whose biological activity is regulated by inhibitors directed on the metal-containing active site. Some metallocarboxypeptidase inhibitors are induced under stress conditions and have a role in defense against pests. This paper is aimed at investigating the response of the tomato metallocarboxypeptidase inhibitor (TCMP)-1 to Cd and other abiotic stresses. To this aim, the tomato TCMP-1 was ectopically expressed in the model species Arabidopsis thaliana, and a yeast two-hybrid analysis was performed to identify interacting proteins. We demonstrate that TCMP-1 is responsive to Cd, NaCl, and abscisic acid (ABA) and interacts with the tomato heavy metal-associated isoprenylated plant protein (HIPP)26. A. thaliana plants overexpressing TCMP-1 accumulate lower amount of Cd in shoots, display an increased expression of AtHIPP26 in comparison with wild-type plants, and are characterized by a modulation in the expression of antioxidant enzymes. Overall, these results suggest a possible role for the TCMP-1/HIPP26 complex in Cd response and compartmentalization

Photoactivation of corticosteroids in UVB-exposed skin.

The photodegradation of flumethasone (FM) and fluocinolone acetonide (FC) was studied in solution and in the pig skin. Both glucocorticosteroids applied to the pig skin were unstable under UVB light. The photoproducts formed in the skin were the lumi-, photolumi- and andro-derivatives for FM, the same found in vitro. Instead, FC hydroperoxide formed in solution was not found in the skin: the reactivity and oxidative ability of this photoproduct towards biological substrates (lipids, proteins) seems the reason of the lack of its detection in the ex vivo model. In fact, it demonstrated to quickly oxidize amino acids and peptides, and to react with BSA both in the dark and under irradiation. Moreover, the presence in the irradiated pig skin of the FC andro-derivative, which usually forms in H-donating environment, seems consistent with the mechanism of Norrish I fragmentation followed by H-abstraction, likely from the surrounding biological substrates. These findings indicate that photoreactivity of these compounds may take place in the skin of patients exposing themselves to sunlight and is a warning about possible skin damage as a result of that. Furthermore, photolability of these drugs in the skin might cause loss of their therapeutic activity

In vitro and ex vivo photostability studies on Flumethasone and Fluocinolone acetonide

Flumethasone and Fluocinolone acetonide are synthetic corticosteroids used topically for the short-term treatment of various inflammatory skin diseases such as eczema, eye, nose, and ear infections, stomatitis and psoriasis. As other 11\uf062-hydroxy corticosteroids, they have shown to be sensitive to light. Previous studies have demonstrated their reactivity under UV light (UVB>UVA) both in organic and aqueous solvents and their main photoproducts have been isolated and characterized. For this high instability to UV irradiation, these drugs may lose their therapeutic activity. Indeed, their packaging instructions always indicate to protect them from light during storage. Moreover, the same problem may arise when patients are exposed to solar radiation. In order to verify the instability of these molecules when applied on the skin under UV light, the photodegradation of the two drugs is studied both in vitro (aqueous solution and commercial formulation) and in the pig skin; this ex vivo model, very close to the human skin, was used to study the fate of drugs in this organ when exposed to light. Both the glucocorticosteroids applied on the pig skin showed high photoinstability under UVB irradiation (up to 40 % for Flumethasone and to 30 % for Fluocinolone acetonide, under 10J/cm2 of UVB). The photoproducts formed in the skin were the same found in vitro, except for the hydroperoxide of Fluocinolone. The very high reactivity of this photoproduct towards biological substrates (i.e. proteins and lipids) could be the reason of the lack of its detection

Obesity and Gastro-Esophageal Reflux voice disorders: a Machine Learning approach

Automatic assessment of speech disorders is a cutting-edge topic in vocal analysis. Recent studies indicated possible connections between eating disorders and voice alterations. In this work, we assessed the influence of obesity and Gastro- Esophageal Reflux Disease (GERD) on voice, being the former a risk factor for the latter. Moreover, we investigated the mutual influence of the diseases working with a consistent set of features. To these aims, we used vocal tests from 92 subjects, with vocal tests consisting of vowel phonation and sentence repetition, and subjects including healthy controls, obese patients, patients with GERD, and obese patients with GERD. Machine Learning models, consisting of Naive Bayes and Support Vector Machine, were successfully employed on extracted features in binary classifications, resulting in 0.86 and 0.82 of accuracies on validation set in scoring the presence of GERD and obesity, respectively. The absence of performance deterioration when moving to the test set denoted a lack of overfitting. As for the tasks and the features employed, the sentence repetition proved to be more effective than the vowel phonation, while Mel Frequency Cepstral Coefficients, Perceptual Linear Prediction Coefficients, Bark Band Energy Coefficients, and noise measures appear to be among the most significant features for the application at han

Photolytic and photocatalytic degradation of fluoroquinolones in untreated river water under natural sunlight

The photodegradation of some among the most frequently prescribed fluoroquinolone antibacterials (FQs) was investigated in untreated river water under solar light as well as under the same conditions in the presence of suspended TiO2. The drugs considered included ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), levofloxacin (LEV), marbofloxacin (MAR) and moxifloxacin (MOX), the last two belonging to the most recent FQ generation. The experiments were carried out in lab-scale batch reactorat concentrations (20–50 ug L−1) comparable to those actually measured in surface waters, and the course of the reaction was monitored by high pressure liquid chromatography (HPLC) with fluorescence detector (FD). A first order kinetics was obeyed upon both direct photolysis and TiO2 heterogeneous photocatalysis. The photoproduced intermediates were identified by HPLC with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and the degradation paths were identified. It was concluded that direct irradiation caused fluorine substitution and reductive elimination, while photocatalysis caused oxidative degradation of the amine side-chain (most efficient with tertiary amines and five-membered cyclic amines). The latter one was a minor process upon direct photolysis and involved hydrogen abstraction by excited states or photoproduced radicals. Photocatalytic decomposition occurred at a rate from two to five times faster than direct photolysis for all of the drugs, except for CIP, that is roughly proportional to the amine oxidation potential. The kinetic constants ranged from 0.061 to 0.66 min−1 in direct photolysis, from 0.22 to 2.78 min−1 in the presence of TiO2. In the latter process, a 90% abatement of the concentration of these otherwise highly persistent drugs was obtained in ca. 15 min. This supports the contention that TiO2 photocatalysis under solar light is a convenient and efficient method for the remediation of pollutants at the ug L−1 levels despite the presence of other non-target matrix constituents. Noteworthy, TiO2 side-chain photo-oxidation was equally effective in the further degradation of the primary intermediates at a rate comparable to that of the parent compounds. The degradation proceeded further so that it could be expected that the antimicrobial activity, related to the FQ quinolone core more than to the substituent pattern, could be effectively eliminated