Soils Drowned in Water Impoundments: A New Frontier

Water impoundments have major impacts on biogeochemical cycles at the local and global scales. However, although reservoirs flood soils, their biogeochemical evolution below water and its ecological consequences are very poorly documented. We took advantage of the complete emptying of the Guerlédan Reservoir (Brittany, France) to compare the composition of soils flooded for 84 years with that of adjacent non-flooded soils used as reference, in 3 situations contrasted by their soil type (Cambisol and Podzol) and initial land-use (forest or grassland). In the annual drawdown zone, upper horizons of submerged soils are eroded, especially near the upper shore and on slopes. In the permanently drowned area, silty sediments cover drowned soils. Compared to reference soils, forest soils drowned for 84 years maintain their original morphological differentiation, but colors are dull, and the humus (O horizons) have virtually disappeared. Spodic horizons are depleted in poorly crystallized iron minerals while the accumulation of amorphous aluminum compounds remains unchanged. Soil bulk density increases as well as pH while total phosphorus content is almost unchanged. On the other hand, the pH of drowned grassland soils is lower by almost one unit, and the total phosphorus content was halved compared to reference soils. In this context, in addition to the effects of flooding, differences are attributed to post-1950 changes in agricultural practices i.e., liming and fertilization. Organic matter stocks decrease by almost 40%. This rate is similar in Cambisols and Podzols. Assuming that carbon was lost as CO2 and CH4, the corresponding flux averaged over the reservoir's life is close to global areal estimates of CO2 emissions in temperate reservoirs and offsets a significant proportion of the carbon burial in reservoir sediments. Hence, flooded soils contribute significantly to the GHG budget of reservoirs, provide original long-term experimental sites to measure the effects of anoxia on soils and contain archives of past soil properties

A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans

Factors affecting drug release from liposomes.

Liposomes are the most widely used nanocarrier systems in medicine. Common strategies for tumor-specific drug delivery using liposomes include the passive accumulation of liposomes that have an increased circulation half-life, which is possible as a result of the leakiness of tumor neovasculature, as well as the active targeting of liposomes using surface-bound ligands. However, such targeting of the nanocarrier is not effective if the encapsulated drug within the liposome is not released at the intended site. Drug release can be influenced by both the membrane composition of the liposome and the choice of drug. In addition to environmental triggers, such as low pH and the presence of particular enzymes, external stimuli such as heat or ultrasound have gained attention in the clinic. This review provides a summary of the various approaches to modifying drug release from liposomes

Thermosensitive liposomal drug delivery systems: state of the art review

Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targetin

Quantification of erufosine, the first intravenously applicable alkylphosphocholine, in human plasma by isotope dilution liquid chromatography-tandem mass spectrometry using a deuterated internal standard.

A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of erucylphosphohomocholine (erufosine, ErPC(3)) in pharmacokinetic studies. Nine-fold deuterated ErPC(3) was used as the internal standard. Following protein precipitation, reversed phase chromatography was performed. For analyte detection, electrospray ionization in the positive mode was applied. The mass transition m/z 504.4>139.1 was recorded for ErPC(3), and the transition m/z 513.7>139.1 for the internal standard, respectively. Good linearity with a correlation coefficient >0.99 was found for the range of 0.48-15 mg/L ErPC(3) in plasma (0.93-29.8 microM), the important range for clinical pharmacokinetic analysis. Interassay coefficients (n=10) of variation between 4.2% and 5.5% were found for ErPC(3) pool samples with concentrations between 4.7 mg/L and 44.0mg/L, respectively. The method has been used for analyses during a phase I clinical trial of ErPC(3)

On the contentious sequence and glycosylation motif of the ribosome inactivating plant protein gelonin

International audienceThe amino acid sequence and the glycosylation motif of the ribosome inactivating protein (RIP) gelonin are identified by Fourier transform ion cyclotron resonance mass spectrometry. Intact gelonin as isolated from the seeds of Gelonium multiflorum consists of at least three different post-translational modified forms: analysis of gelonin peptides as obtained by proteolytic digestion is consistent with the amino acid sequence published by Nolan et al. High resolution mass determination established a glycosylation pattern of GlcNAc2Man3-5Xyl. N189 was identified as glycosylation site. The proposed glycan structure is consistent with a standard plant N-glycosylation pattern as found in other RIP. Based on these results we suggest that gelonin is located in the vacuole of Gelonium multiflorum seeds. © 2005 Elsevier Inc. All rights reserved

In vitro characterization of phosphatidylglyceroglycerol-based thermosensitive liposomes with encapsulated 1H MR T1-shortening gadodiamide.

Thermosensitive liposomes (TSL) with encapsulated proton (1H) magnetic resonance (MR) contrast agents have been proposed for noninvasive online temperature monitoring during tumor treatment using chemotherapy combined with hyperthermia (HT). The technique exploits the fact that water exchange between the TSL interior and exterior is increased and/or the encapsulated 1H MR contrast agent is released near the gel-to-liquid crystalline phase transition temperature (Tm) of TSL and thus shortens the 1H MR relaxation time of tissue. In this work, newly developed, phosphatidylglyceroglycerol (DPPGOG)-based TSL with encapsulated 1H MR longitudinal relaxation time (T1)-shortening gadodiamide (Gd-DTPA-BMA) were characterized in vitro by measuring the temperature dependence of the T1 of these gadodiamide-containing DPPGOG-TSL samples between 30 and 50 degrees C. The measurements revealed that the T1 nonlinearly slightly decreased with increasing temperature from 30 to 37 degrees C, mainly due to increased water exchange between the gadodiamide-containing DPPGOG-TSL interior and exterior with the exception of negligible gadodiamide release. This implies that gadodiamide-containing DPPGOG-TSL were stable at temperatures < or =37 degrees C, which was also confirmed by an independent stability study. From 37 to 44 degrees C, the T1 nonlinearly markedly decreased with increasing temperature since encapsulated gadodiamide was rapidly released. Above 44 degrees C, gadodiamide was completely released and the T1 was directly proportional to temperature while heated from 44 to 50 degrees C and cooled from 50 to 30 degrees C, respectively. Additionally, gadodiamide release was theoretically quantified and this calculated concentration was consistent with the actually released amount directly obtained from the cooling course of empty DPPGOG-TSL with completely released gadodiamide