During neuroinflammation, cytokines such as TNF-α and IFN-γ secreted by activated leukocytes and/or CNS resident cells have been shown to alter the phenotype and function of brain endothelial cells ...(BECs) leading to blood-brain barrier breakdown. In this study, we show that the human BEC line hCMEC/D3 expresses the receptors for TNF-α, TNF receptor 1 and TNF receptor 2, and for IFN-γ. BEC activation with TNF-α alone or in combination with IFN-γ induced endothelial leakage of paracellular tracers. At high cytokine concentrations (10 and 100 ng/ml), this effect was associated with caspase-3/7 activation and apoptotic cell death as evidenced by annexin V staining and DNA fragmentation (TUNEL) assays. In addition, inhibition of JNK and protein kinase C activation at these doses partially prevented activation of caspase-3/7, although only JNK inhibition was partially able to prevent the increase in BEC paracellular permeability induced by cytokines. By contrast, lower cytokine concentrations (1 ng/ml) also led to effector caspase activation, increased paracellular flux, and redistribution of zonula occludens-1 and VE-cadherin but failed to induce apoptosis. Under these conditions, specific caspase-3 and caspase-9, but not caspase-8, inhibitors partially blocked cytokine-induced disruption of tight and adherens junctions and BEC paracellular permeability. Our results suggest that the concentration of cytokines in the CNS endothelial microenvironment determines the extent of caspase-mediated barrier permeability changes, which may be generalized as a result of apoptosis or more subtle as a result of alterations in the organization of junctional complex molecules.
Blood-brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is ...diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS.
The objetive of the current study was to determine the effect of maternal energy status during late gestation on growth performance, carcass characteristics and meat quality of steer progeny. At ...180 ± 4 d of gestation 56 multiparous Angus cows were blocked by BW and expected calving date and asigned to three levels of nutrition energy: SR (severe restricted; 50% of NRC requirement), MR (moderate restricted; 75% of requirement) and NR (no restricted; 100% of requirement). After parturition, all cows were managed in a single group during lactation. A total of 25 male calves (SR = 8 calves; MR = 9 calves; NR = 8 calves) were born from pregnant cows and all pens had at least one male calf. After weaning, male calves were separated of female calves and were stockered on native range until 24 ± 0.1 months of age then placed into a feedlot for 104 d before harvest. Cow BW and BCS decreased linearly (P < .01) as nutritional energy restriction increased. Calves from SR dams were lighter (P = .04) than calves from MR and NR dams at parturition, however, at weaning and harvest BW was similar for SR and NR steers and decreased in MR steers. Steers from SR dams demonstrated catch-up growth with a tendecy to increased ADG from birth to harvest compared to MR and NR steers (P = .06). Hot carcass weigth was similar in SR and NR steers and increased in MR steers (P = .01). Longissimus muscle area was not affected (P > .10) by maternal energy status, however, 12 rib fat thickness was greater in SR and MR compared to NR steers (P < .01). Tenderness of Longissimus muscle was decreased in MR compared to SR and NR steers after 3d of aging. No treatment differences (P > .10) were observed in sarchomere length or collagen content. Adipocyte diameter was similar (P > .10) between treatments suggesting that decreased 12th rib fat thicness in MR steers could be due to decreased fat tissue hyperplasia. These results indicate that level of energy restriction during late gestation does no have linear response on growth performance and carcass quality of steers progeny.
Abstract P-glycoprotein (P-gp) expression at the blood–brain barrier prevents unwanted blood-borne toxins and signalling molecules from entering the brain. Primary and immortalised human brain ...endothelial cells (BECs) represent two suitable options for studying P-gp function in vitro . The limited supply of primary human BECs and their instability over passage number make this choice unattractive for medium/high throughput studies. The aim of this study was to further characterise the expression of P-gp by an immortalised human BEC line, hCMEC/D3, in order to evaluate their use as an in vitro human blood–brain barrier model. P-gp expression was stable over a high passage number (up to passage 38) and was polarised on the apical plasma membrane, consistent with human BECs in vivo . In addition, hCMEC/D3 cell P-gp expression was comparable, albeit slightly lower to that observed in primary isolated human BECs although P-gp function was similar in both cell lines. The P-gp inhibitors tariquidar and vinblastine prevented the efflux of rhodamine 123 (rh123) from hCMEC/D3 cells, indicative of functional P-gp expression. hCMEC/D3 cells also displayed polarised P-gp transport, since both tariquidar and vinblasine selectively increased the apical-to-basolateral permeability of hCMEC/D3 cells to rh123. The results presented here demonstrate that hCMEC/D3 cells are a suitable model to investigate substrate specificity of P-gp in BECs of human origin.
Under a global warming scenario, it is important to adopt practices that favor soil water conservation, such as plant intercropping systems and the use of plastic mulching. The objective of this ...study was to determine how microenvironment, morphology, productivity and quality of jalapeño peppers were affected by corn intercropping and the use of plastic mulching. Two experiments were conducted during 2015 and 2016 in the Valley of Mexicali, Mexico, a region characterized by its extreme aridity, soil salinity, hot temperatures and high radiation during the summer. Four treatments were tested: jalapeño peppers grown on bare soil (BS); on bare soil intercropped with corn (BS+IC); on plastic mulch (PMu); and on plastic mulch intercropped with corn (PMu+IC). The response variables measured were yield, fruit quality attributes, microclimatic variables, and morphology of the pepper crop. PMu treatment produced the tallest pepper plants and yields, while the BS+IC treatment produced the smallest plants and the lowest yields. A possible explanation for the higher biomass and crop yield of the PMu treatment is the lack of competition from corn and the effect of plastic mulching in reducing soil salinity. It is concluded that competition from corn on jalapeño pepper dramatically affected the pepper’s productivity, particularly under high soil salinity and extremely high temperature conditions.
Report of Colombian Registry for Hereditary Angioedema Olivares, Maria Margarita, MD; Farfan, Rosa, MD; Olmos, Carlos E., MD ...
Journal of allergy and clinical immunology,
02/2016, Letnik:
137, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The average age of onset of symptoms was 23 years old, with an average age at diagnosis of 37 years. 88.23% with positive family history for the disease. 62% of patients are currently in maintenance ...treatment: 48% with danazol, tranexamic acid 12.07%; 38.9% of patients used Icatiban for handling the acute crisis.
Ag-ZnO/MWCNT composites were obtained by microwave-assisted, varying-charge synthesis of multiwalled carbon nanotubes (MWCNT). The structural, morphological and optical properties were characterized ...by: XRD, SEM, TEM, Physisorption of N2 and UVVis. The incorporation of Ag ions and MWNTC caused changes in the structure tension and in the average crystallite size of ZnO. The micrographs revealed that ZnO agglomerates were distributed on the MWNTC and that Ag particles were deposited on the surface of the heterostructure, thus the energy gap decreased. The percentages of degradation of methylene blue were 98 and 75% under ultraviolet and visible radiation, respectively, in the Ag-ZnO/CNT composites.
TiO2, TiO2-Cu, TiO2-CNTs y TiO2-CNTs-Cu films were obtained by Dip-coating technique and 500°C for 1h. The Anatase phase of TiO2 was identified and the TiO2-Cu film also presented the Tenorite ...secondary phase of CuO. The planes (101) and (200) of the Graphite 2H phase were identified in the films with CNTs. The crystal size was obtained between 5 to 16 nm. The morphology is homogeneous without pores and without cracks. The bandgap value for TiO2-CNTs-Cu and TiO2 films were 3.22 and 3.48 eV respectively. For photocatalytic evaluation Visible and UV irradiation were used and TiO2-CNTs showed a degradation of 53%.
Background In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. Study Design Longitudinal cohort study. Setting & ...Participants 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. Predictors Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. Outcomes & Measurements Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N -acetyl-β- d -glucosaminidase (NAG), and albumin; serum creatinine–based estimated glomerular filtration rate (eGFR). Results Mean eGFR was 113 mL/min/1.73 m2 and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non–field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, −0.6 to 6.7) mL/min/1.73 m2 , respectively. Limitations Surrogate exposure measure, loss to follow-up. Conclusions Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.
The ZnSe/ZnO heterostructures were synthesized with the microwave-assisted hydrothermal method, using zinc acetate and zinc nitrate as a source of Zn2+ ions. Materials were characterized by X-ray ...diffraction (XRD), X-ray photoemitted electron spectroscopy (XPS), Raman spectroscopy, and scanning electron microscopy (SEM). The incorporation of ZnSe into the ZnO matrix produced changes both in the size of the ZnO crystallites and in the lattice parameters. Optical and texture analyses revealed that ZnSe particles cause a decrease in gap energy and a greater than 90% increase in the specific surface area of ZnSe/ZnO heterostructures compared to bare ZnO particles. ZnSe/ZnO heterostructures synthesized using zinc acetate as a Zn ion source exhibited better photocatalytic performance in visible light compared to pure ZnO.
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