Ability of plasmid DNA complexed with histidinylated lPEI and lPEI to cross in vitro lung and muscle vascular endothelial barriers

DNA complexes made with cationic polymers (polyplexes) developed as nonviral vectors for gene therapy must be enabled to cross through vascular endothelium to transfect underlying tissues upon their administration in the blood circulation. Here, we evaluated the transendothelial passage (TEP) of DNA complexes made with histidinylated linear polyethylenimine (His-lPEI) or linear polyethylenimine (lPEI). In vitro studies were performed by using established transwell lung and skeletal muscle vascular endothelial barriers. The models were composed of a monolayer of human lung microvascular endothelial (HMVEC-L) cells and mouse cardiac endothelial (MCEC) cells formed on a PET insert and immortalized human tracheal epithelial (ΣCFTE29o-) cells and mouse myoblasts (C2C12) as target cells cultured in the lower chamber, respectively. When the vascular endothelium monolayer was established and characterized, the transfection efficiency of target (ΣCFTE29o- and C2C12) cells with plasmid DNA encoding luciferase was used to evaluate TEP of polyplexes. The luciferase activities with His-lPEI and lPEI polyplexes compared to those obtained in the absence of endothelial cell monolayer were 6.5% and 4.3% into ΣCFTE29o- cells, and 18.5% and 0.23% into C2C12 cells, respectively. The estimated rate for His-lPEI polyplexes was 0.135 μg/cm².h and 0.385 μg/cm².h through the HMVEC-L and MCEC monolayers, respectively. These results indicate that His-lPEI polyplexes can pass through the lung and skeletal muscle vascular endothelium and can transfect underlying cells.     

Caractérisation des adénopathies médiastinales en TEP/TDM au 18F-FDG

The mediastinum is a complex anatomical region located at the junction of the cervical, thoracic and abdominal regions. It is an important lymphatic gateway that has an impact in many pathologies with nodal involvement and for which ¹⁸F-FDG PET/CT is a central examination. In this review article, we propose to recall the normal and pathological lymphatic drainage, mediastinum anatomy, the International Association for the Study of Lung Cancer (IASLC) lymph node classification and its implications in lung cancer. Then we will detail the morphological and metabolic characteristics, principal etiologies and the procedures to access mediastinal lymph nodes.     

Apport de la TEP/TDM au 18FDG dans le bilan préopératoire des phéochromocytomes. Étude rétrospective comparative par rapport à la scintigraphie à la MIBG

Pheochromocytomas (PHEO) are tumors arisen from the adrenal medulla, with a high secretory risk. Malignancy is rare and difficult to establish before metastastic spread. The risk of multifocality becomes greater whether genetic predisposition exists. MIBG scintigraphy is the reference functional imaging of PHEO. The place of 18FDG PET/CT is not well-established in literature. Our study retrospectively analyzes patients operated for a PHEO and who underwent both MIBG and 18FDG PET/CT before surgery, between 2007 and 2015. On the 49 patients included (52 lesions), among them 13 had genetic mutation, MIBG detected 39 lesions (75%) and 18FDG PET/CT forty-eight (92%), enabling a combined sensitivity of 98%. Sensitivity was not affected by the predominant secretion (metanephrine or normetanephrine), whereas MIBG-negative lesions showed a higher proliferation index (Ki67) than MIBG-positive lesions (6.6 vs. 2.8; P = 0.0044). FDG PET/CT semi-quantitative indices vary with the germline mutation status and were significantly higher for Cluster 1 lesions (SDHx, VHL or FH mutations) than for any other lesions (SUVmax = 27.73 vs. 5.92 for the others mutations (Cluster 2), 9.53 for lesions without mutation and 3.78 for undetermined lesions; P = 0.002). In conclusion, because of their capacity to take up FDG, 18FDG PET/CT could be useful in the preoperative imaging of PHEO, especially when MIBG is not contributive or when F-DOPA PET/CT is not available. An intense FDG uptake may orient to a Cluster 1 mutation.     

The carbohydrates of Phaeocystis and their degradation in the microbial food web

The ubiquity and high productivity associated with blooms of colonial Phaeocystis makes it an important contributor to the global carbon cycle. During blooms organic matter that is rich in carbohydrates is produced. We distinguish five different pools of carbohydrates produced by Phaeocystis. Like all plants and algal cells, both solitary and colonial cells produce (1) structural carbohydrates, (hetero) polysaccharides that are mainly part of the cell wall, (2) mono- and oligosaccharides, which are present as intermediates in the synthesis and catabolism of cell components, and (3) intracellular storage glucan. Colonial cells of Phaeocystis excrete (4) mucopolysaccharides, heteropolysaccharides that are the main constituent of the mucous colony matrix and (5) dissolved organic matter (DOM) rich in carbohydrates, which is mainly excreted by colonial cells. In this review the characteristics of these pools are discussed and quantitative data are summarized. During the exponential growth phase, the ratio of carbohydrate-carbon (C) to particulate organic carbon (POC) is approximately 0.1. When nutrients are limited, Phaeocystis blooms reach a stationary growth phase, during which excess energy is stored as carbohydrates. This so-called overflow metabolism increases the ratio of carbohydrate-C to POC to 0.4–0.6 during the stationary phase, leading to an increase in the C/N and C/P ratios of Phaeocystis organic matter. Overflow metabolism can be channeled towards both glucan and mucopolysaccharides. Summarizing the available data reveals that during the stationary phase of a bloom glucan contributes 0–51% to POC, whereas mucopolysaccharides contribute 5–60%. At the end of a bloom, lysis of Phaeocystis cells and deterioration of colonies leads to a massive release of DOM rich in glucan and mucopolysaccharides. Laboratory studies have revealed that this organic matter is potentially readily degradable by heterotrophic bacteria. However, observations in the field of accumulation of DOM and foam indicate that microbial degradation is hampered. The high C/N and C/P ratios of Phaeocystis organic matter may lead to nutrient limitation of microbial degradation, thereby prolonging degradation times. Over time polysaccharides tend to self-assemble into hydrogels. This may have a profound effect on carbon cycling, since hydrogels provide a vehicle to move DOM up the size spectrum to sizes subject to sedimentation. In addition, it changes the physical nature and microscale structure of the organic matter encountered by bacteria which may affect the degradation potential of the Phaeocystis organic matter.     

Primary lymphoma of the prostate: A report of two cases

The primary lymphoma of prostate is rare, representing 0.2–0.8% of extranodal lymphomas and 0.1% of all prostate neoplasias.     

Increased Arterial PET/CT 18F-Fluorodeoxyglucose Uptake in Obese and Overweight Patients

ObjectivesWe aimed to investigate the association between BMI and early atherosclerotic activity in cancer patients. We also compared the inflammatory and macroscopic calcification processes of atherosclerosis in the aortic segments and large arteries by ¹⁸F-FDG PET/CT of between normal and high BMI patients.MethodsWe conducted a retrospective review of cancer patients presented to our institution within the period between February and May 2018. Patients were classified according to their BMI into two groups: normal BMI group and high BMI group. Data of average SUVmax and SUVmean for four segments of the aorta, common iliac arteries, and femoral arteries were estimated and compared between both groups. Moreover, the macroscopic calcification on CT images for each vascular section was also reported.ResultsNinety-eight patients were classified into two groups: normal BMI group (n = 52; 53.1%), and high BMI group (n = 46; 46.9%). Average SUVmax was significantly higher in obese participants in all arterial segments (P < 0.05). However, the SUVmean was significantly higher in obese patients in only three arterial segments aortic arch, left femoral artery and descending thoracic aorta (P < 0.05).Moreover, the differences between the two study groups in terms of the frequency of macroscopic calcifications were not statistically significant for all vascular segments. BMI positively correlated with SUVmax and SUVmean of the vascular segments (r value from 0,219 to 0,575/p value between 0,023 and 0,0001).ConclusionsFluorine-18-FDG PET/CT imaging revealed that patients with high BMI have more accelerated atherosclerotic inflammatory process in their major vessels compared to their age-matched controls with normal BMI. Future studies should assess the associated between these findings and the cardiovascular events in the long term.     

Dissolved organic matter (DOM) release by phytoplankton in the contemporary and future ocean

The partitioning of organic matter (OM) between dissolved and particulate phases is an important factor in determining the fate of organic carbon in the ocean. Dissolved organic matter (DOM) release by phytoplankton is a ubiquitous process, resulting in 2–50% of the carbon fixed by photosynthesis leaving the cell. This loss can be divided into two components: passive leakage by diffusion across the cell membrane and the active exudation of DOM into the surrounding environment. At present there is no method to distinguish whether DOM is released via leakage or exudation. Most explanations for exudation remain hypothetical; as while DOM release has been measured extensively, there has been relatively little work to determine why DOM is released. Further research is needed to determine the composition of the DOM released by phytoplankton and to link composition to phytoplankton physiological status and environmental conditions. For example, the causes and physiology of phytoplankton cell death are poorly understood, though cell death increases membrane permeability and presumably DOM release. Recent work has shown that phytoplankton interactions with bacteria are important in determining both the amount and composition of the DOM released. In response to increasing CO₂ in the atmosphere, climate change is creating increasingly stressful conditions for phytoplankton in the surface ocean, including relatively warm water, low pH, low nutrient supply and high light. As ocean physics and chemistry change, it is hypothesized that a greater proportion of primary production will be released directly by phytoplankton into the water as DOM. Changes in the partitioning of primary production between the dissolved and particulate phases will have bottom-up effects on ecosystem structure and function. There is a need for research to determine how these changes affect the fate of organic matter in the ocean, particularly the efficiency of the biological carbon pump.     

Distribution and characterization of dissolved and particulate organic matter in Antarctic pack ice

Distribution and composition of organic matter were investigated in Antarctic pack ice in early spring and summer. Accumulation of organic compounds was observed with dissolved organic carbon (DOC) and particulate organic carbon (POC) reaching 717 and 470 μM C, respectively and transparent exopolymeric particles (TEP) up to 3,071 μg Xanthan gum equivalent l⁻¹. POC and TEP seemed to be influenced mainly by algae. Particulate saccharides accounted for 0.2–24.1% (mean, 7.8%) of POC. Dissolved total saccharides represented 0.4–29.6% (mean, 9.7%) of DOC, while dissolved free amino acids (DFAA) accounted for only 1% of DOC. Concentrations of TEP were positively correlated with those of saccharides. Monosaccharides (d-MCHO) dominated during winter–early spring, whereas dissolved polysaccharides did in spring–summer. DFAA were strongly correlated with d-MCHO, suggesting a similar pathway of production. The accumulation of monomers in winter is thought to result from limitation of bacterial activities rather than from the nature of the substrates.