Efficacy of combination of localized closure, ethacridine lactate dressing, and phototherapy in treatment of severe extravasation injuries: A case series.

BACKGROUND: The management of severe extravasation injuries is still controversial. Extravasation injuries can be treated in many ways. AIM: To present a series of patients with severe extravasation injuries due to infusion who were managed with ethacridine lactate dressing combined with localized closure and phototherapy. METHODS: In this study, we evaluated the data of eight patients, including six from the Department of Burn, one (with colorectal carcinoma) from the Veteran Cadre Department, and one (with leukemia) from the Hematology Department. Of these, three patients were male and five were female. Age of the patients ranged from 10 mo to 72 years, including two children (10 and 19 mo of age). In this study, the infusion was stopped immediately when the extravasation was identified. The extravasation event was managed routinely using a blocking solution. A ring-shaped localized closure was performed using the blocking agents. Moreover, ethacridine lactate dressing and phototherapy were applied for 3-5 d. RESULTS: In this study, the drugs contained in the infusates were iodixanol, norepinephrine, alprostadil, amino acids, fat emulsion, cefoselis, cefoxitin, and potassium chloride + concentrated sodium chloride. All of the patients achieved complete healing after treatment and no obvious adverse reactions were observed. CONCLUSION: The treatment of severe extravasation injuries using a combination of localized closure, ethacridine lactate dressing, and phototherapy resulted in satisfactory outcomes in patients.

Signatures of mast cell activation are associated with severe COVID-19

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.

The Arabidopsis AtGCD3 protein is a glucosylceramidase that preferentially hydrolyzes long-acyl-chain glucosylceramides.

Cellular membranes contain many lipids, some of which, such as sphingolipids, have important structural and signaling functions. The common sphingolipid glucosylceramide (GlcCer) is present in plants, fungi, and animals. As a major plant sphingolipid, GlcCer is involved in the formation of lipid microdomains, and the regulation of GlcCer is key for acclimation to stress. Although the GlcCer biosynthetic pathway has been elucidated, little is known about GlcCer catabolism, and a plant GlcCer-degrading enzyme (glucosylceramidase (GCD)) has yet to be identified. Here, we identified AtGCD3, one of four Arabidopsis thaliana homologs of human nonlysosomal glucosylceramidase, as a plant GCD. We found that recombinant AtGCD3 has a low Km for the fluorescent lipid C6-NBD GlcCer and preferentially hydrolyzes long acyl-chain GlcCer purified from Arabidopsis leaves. Testing of inhibitors of mammalian glucosylceramidases revealed that a specific inhibitor of human ß-glucosidase 2, N-butyldeoxynojirimycin, inhibits AtGCD3 more effectively than does a specific inhibitor of human ß-glucosidase 1, conduritol ß-epoxide. We also found that Glu-499 and Asp-647 in AtGCD3 are vital for GCD activity. GFP-AtGCD3 fusion proteins mainly localized to the plasma membrane or the endoplasmic reticulum membrane. No obvious growth defects or changes in sphingolipid contents were observed in gcd3 mutants. Our results indicate that AtGCD3 is a plant glucosylceramidase that participates in GlcCer catabolism by preferentially hydrolyzing long-acyl-chain GlcCers.

Diagnostic value of water swallow test and simple two-step swallowing provocation test for aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD) / 中国实用内科杂志

OBJECTIVE: To explore the value of water swallow test(WST)and simple two-step swallowing provocation test(SSPT)in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS:87 hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease were recruited from the First Affiliated Hospital of Guangzhou Medical University during the period between December 2014 to December 2015. RESULTS: The number of patients of grade1,2,3,4 and 5 of water swallow test successively were 44,39,4,0 and 0. Patients with positive aspiration by the first-step(water injection of 0.4 mL)and the second-step(water injection of 2.0 m L)were 16 and 0. Patients with positive aspiration by radionuclide imaging was 35. Comparison of radionuclide imaging, the rate of missed diagnosis applying water swallow test was high 37.3%(31/83). Both the water swallow test and simple two-step swallowing provocation test have poor consistency with radionuclide imaging in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(McNemar consistency test P=0.00).CONCLUSION: There is a high rate of missed diagnosis applying water swallow test and simple two-step swallowing provocation test to diagnosis aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and combined use of multiple assessment methods can reduce the missed diagnosis rate of aspiration.

Orosomucoid Proteins Interact with the Small Subunit of Serine Palmitoyltransferase and Contribute to Sphingolipid Homeostasis and Stress Responses in Arabidopsis.

Serine palmitoyltransferase (SPT), a pyridoxyl-5'-phosphate-dependent enzyme, catalyzes the first and rate-limiting step in sphingolipid biosynthesis. In humans and yeast, orosomucoid proteins (ORMs) negatively regulate SPT and thus play an important role in maintaining sphingolipid levels. Despite the importance of sphingoid intermediates as bioactive molecules, the regulation of sphingolipid biosynthesis through SPT is not well understood in plants. Here, we identified and characterized the Arabidopsis thaliana ORMs, ORM1 and ORM2. Loss of function of both ORM1 and ORM2 (orm1 amiR-ORM2) stimulated de novo sphingolipid biosynthesis, leading to strong sphingolipid accumulation, especially of long-chain bases and ceramides. Yeast two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays confirmed that ORM1 and ORM2 physically interact with the small subunit of SPT (ssSPT), indicating that ORMs inhibit ssSPT function. We found that orm1 amiR-ORM2 plants exhibited an early-senescence phenotype accompanied by H2O2 production at the cell wall and in mitochondria, active vesicular trafficking, and formation of cell wall appositions. Strikingly, the orm1 amiR-ORM2 plants showed increased expression of genes related to endoplasmic reticulum stress and defenses and also had enhanced resistance to oxidative stress and pathogen infection. Taken together, our findings indicate that ORMs interact with SPT to regulate sphingolipid homeostasis and play a pivotal role in environmental stress tolerance in plants.

An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress.

Ceramidases hydrolyze ceramide into sphingosine and fatty acids and, although ceramidases function as key regulators of sphingolipid homeostasis in mammals, their roles in plants remain largely unknown. Here, we characterized the Arabidopsis thaliana ceramidase AtNCER1, a homolog of human neutral ceramidase. AtNCER1 localizes predominantly on the endoplasmic reticulum. The ncer1 T-DNA insertion mutants had no visible phenotype, but accumulated hydroxyceramides, and showed increased sensitivity to oxidative stress induced by methyl viologen. Plants over-expressing AtNCER1 showed increased tolerance to oxidative stress. These data indicate that the Arabidopsis neutral ceramidase affects sphingolipid homeostasis and oxidative stress responses.

The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance.

Ceramidases hydrolyze ceramide into sphingosine and fatty acids. In mammals, ceramidases function as key regulators of sphingolipid homeostasis, but little is known about their roles in plants. Here we characterize the Arabidopsis ceramidase AtACER, a homolog of human alkaline ceramidases. The acer-1 T-DNA insertion mutant has pleiotropic phenotypes, including reduction of leaf size, dwarfing and an irregular wax layer, compared with wild-type plants. Quantitative sphingolipid profiling showed that acer-1 mutants and the artificial microRNA-mediated silenced line amiR-ACER-1 have high ceramide levels and decreased long chain bases. AtACER localizes predominantly to the endoplasmic reticulum, and partially to the Golgi complex. Furthermore, we found that acer-1 mutants and AtACER RNAi lines showed increased sensitivity to salt stress, and lines overexpressing AtACER showed increased tolerance to salt stress. Reduction of AtACER also increased plant susceptibility to Pseudomonas syringae. Our data highlight the key biological functions of ceramidases in biotic and abiotic stresses in plants.

Loss of ceramide kinase in Arabidopsis impairs defenses and promotes ceramide accumulation and mitochondrial H2O2 bursts.

Arabidopsis thaliana plants that lack ceramide kinase, encoded by ACCELERATED CELL DEATH5 (ACD5), display spontaneous programmed cell death late in development and accumulate substrates of ACD5. Here, we compared ceramide accumulation kinetics, defense responses, ultrastructural features, and sites of reactive oxygen species (ROS) production in wild-type and acd5 plants during development and/or Botrytis cinerea infection. Quantitative sphingolipid profiling indicated that ceramide accumulation in acd5 paralleled the appearance of spontaneous cell death, and it was accompanied by autophagy and mitochondrial ROS accumulation. Plants lacking ACD5 differed significantly from the wild type in their responses to B. cinerea, showing earlier and higher increases in ceramides, greater disease, smaller cell wall appositions (papillae), reduced callose deposition and apoplastic ROS, and increased mitochondrial ROS. Together, these data show that ceramide kinase greatly affects sphingolipid metabolism and the site of ROS accumulation during development and infection, which likely explains the developmental and infection-related cell death phenotypes. The acd5 plants also showed an early defect in restricting B. cinerea germination and growth, which occurred prior to the onset of cell death. This early defect in B. cinerea restriction in acd5 points to a role for ceramide phosphate and/or the balance of ceramides in mediating early antifungal responses that are independent of cell death.