| 1. |
- Gatto, Francesco, 1987, et al.
(författare)
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Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 15:8, s. 1822-1836
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis.
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| 2. |
- Gillen, Michael, et al.
(författare)
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Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort® (budesonide/formoterol) pressurized metered dose inhaler
- 2018
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Ingår i: Pulmonary Pharmacology and Therapeutics. - : Elsevier BV. - 1094-5539 .- 1522-9629. ; 52, s. 7-17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 μg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device. Methods: A Phase I, randomized, open-label, single-dose, single-center, crossover study in 50 healthy volunteers (NCT02934607) assessed the relative bioavailability of single-dose Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) with and without a spacer (AeroChamber Plus® Flow-Vu®). Inhaled doses were administered without or with activated charcoal (taken orally) to estimate total systemic exposure and exposure through the lung, respectively. The in vitro study characterized the effect of the spacer with respect to delivered dose, fine particle dose, and dose during simulated breathing of budesonide and formoterol. Results: In terms of total systemic exposure, use of the spacer increased the relative bioavailability determined by AUC(0-last) and Cmax by 68% (spacer:no spacer treatment ratio, 167.9%; 90% CI, 144.1 to 195.6) and 99% (ratio, 198.7%; 90% CI, 164.4 to 240.2) for budesonide, and 77% (ratio, 176.6%; 90% CI, 145.1 to 215.0) and 124% (ratio, 223.6%; 90% CI, 189.9 to 263.3) for formoterol, respectively, compared with pMDI alone. Similarly, the lung exposure of budesonide and formoterol increased (AUC(0-last) and Cmax by 146% [ratio, 246.0%; 90% CI, 200.7 to 301.6] and 127% [ratio, 226.5%; 90% CI, 186.4 to 275.4] for budesonide, and 173% [ratio, 272.8%; 90% CI, 202.5 to 367.4] and 136% [ratio, 236.2%; 90% CI, 192.6 to 289.6] for formoterol, respectively) when the pMDI was administered through the spacer. When assessed by AUC(0-last) quartile without spacer, subjects in the lowest exposure quartile (indicating poor inhalation technique) with Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) had markedly increased total systemic and lung exposure when the same dose was administered with the spacer. In contrast, for subjects in the highest exposure quartile with pMDI alone, total systemic and lung exposure of formoterol and budesonide was similar with and without the spacer. In the in vitro study, the fine particle dose (<5 μm) of both budesonide and formoterol from the spacer at delay time (i.e. pause period after actuation) = 0 s (instantaneous) after actuation was similar to the fine particle dose when not using the spacer. The delivered doses of budesonide and formoterol from the spacer were both lower compared with the doses administered without the spacer. There was also a decrease in delivered dose with increasing delay time. Conclusions: The clinical study demonstrated that in subjects with poor inhalation technique the use of the AeroChamber Plus® Flow-Vu® spacer increased the bioavailability of Symbicort® pMDI to a level observed in subjects with good inhalation technique without a spacer. The findings from the in vitro study support the fine particle dose characteristics of Symbicort® pMDI with the AeroChamber Plus® Flow-Vu® spacer.
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| 3. |
- Ritter, Camila, et al.
(författare)
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Environmental impact assessment in Brazilian Amazonia: Challenges and prospects to assess biodiversity
- 2017
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 206, s. 161-168
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The AuthorsEnvironmental Impact Assessment (EIA) has the goal of providing decision makers with an indication of the likely environmental consequences of planned actions risking environmental changes and, when necessary, allowing revision of these actions to mitigate adverse impacts. Here we provide an overview of the efficiency of EIA with emphasis on Brazilian Amazonia and discuss the problems and challenges with this type of assessment in highly diverse ecosystems. We concentrate on the methodology and performance of EIAs for three of the most recent and largest infrastructure projects in Amazonia: the Belo Monte hydroelectric dam, the BR-319 Highway, and the Juruti bauxite mine. We conclude that all of these EIAs fall short of properly assessing the expected impact of infrastructure development in situ, and that their results had little or no effect on policy decisions. To improve the reliability and usefulness of EIAs in biologically diverse ecosystems, we suggest three relatively fast and cost-effective complementary approaches for assessing biodiversity: remote sensing, reflectance spectroscopy, and DNA meta-barcoding. We discuss how these emerging cutting-edge techniques can help in identifying environmental threats and the consequences of different activities in Amazonia. The ability to monitor the state of the environment and the likely impacts of human activities on natural resources is fundamental to evidence-based decisions on development choices, to the design of appropriate management strategies, and to mitigate biological and ecological consequences.
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