ABSTRACT
Hydrofluoric acid inhalation injury is difficult to treat, despite it has low incidence. It could cause mild symptoms such as cough and sore throat, or severe symptom that may develop into life-threatening acute respiratory distress syndrome, and even rare pulmonary diseases such as reactive airway dysfunction syndrome and pulmonary alveolar proteinosis. Currently, there is no specific standard for the diagnosis and treatment of hydrofluoric acid inhalation injury. Authors summarize the incidence, injury mechanism, clinical diagnosis and treatment of hydrofluoric acid inhalation injury by searching literature at home and abroad and propose that pulse contour cardiac output monitor and extracorporeal membrane oxygenation have great application prospects in treatment of severe cases, so as to provide references for peers.
Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Humans , Hydrofluoric Acid , Lung , Respiration, ArtificialSubject(s)
Hemophilia A/diagnosis , Leukemia, Myelomonocytic, Chronic/diagnosis , Aged , Antineoplastic Agents/therapeutic use , Coagulants/analysis , Coagulants/therapeutic use , Factor VIII/analysis , Factor VIII/therapeutic use , Hematuria/pathology , Hemophilia A/complications , Hemophilia A/drug therapy , Humans , Hydroxyurea/therapeutic use , Leukemia, Myelomonocytic, Chronic/complications , Leukemia, Myelomonocytic, Chronic/drug therapy , Leukocyte Count , Male , Partial Thromboplastin Time , Recombinant Proteins/therapeutic useABSTRACT
BACKGROUND: Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. OBJECTIVES: The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. METHODS: Fluorogenic, surface-enhanced laser desorption/ionization time-of-flight mass spectrometric assay, and Western blotting analyses were used to address this question. RESULTS: Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration of ~13, ~70, and ~17 µmol L(-1) , respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia increased after treatment with bilirubin oxidase. CONCLUSIONS: Unconjugated bilirubin directly inhibits ADAMTS13's ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has prothrombotic effect in vivo remains to be determined in our future study.
Subject(s)
ADAM Proteins/metabolism , Bilirubin/metabolism , Hyperbilirubinemia/enzymology , Protease Inhibitors/metabolism , von Willebrand Factor/metabolism , ADAM Proteins/antagonists & inhibitors , ADAM Proteins/blood , ADAMTS13 Protein , Bilirubin/blood , Bilirubin/pharmacology , Blotting, Western , Dose-Response Relationship, Drug , Humans , Hyperbilirubinemia/blood , Hyperbilirubinemia/diagnosis , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Protease Inhibitors/blood , Protease Inhibitors/pharmacology , Proteolysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
We demonstrated that non-adherent BM cells (NA-BMCs) can be expanded in suspension and give rise to multiple mesenchymal phenotypes including fibroblastic, osteoblastic, chondrocytic and adipocytic as well as glial cell lineages in vitro using the 'pour-off' BMC culture method. Mesenchymal stem cells (MSCs) derived from NA-BMCs (NA-MSCs) from wild-type mice were transplanted into VDR gene knockout (VDR(-/-)) mice that had received a lethal dose of radiation. Results revealed that NA-MSC can be used to rescue lethally irradiated mice and become incorporated into a diverse range of tissues. After lethal dose irradiation, all untransplanted mice died within 2 weeks, whereas those transplanted with NA-MSCs were viable for at least 3 months. Transplantation rescued these mice by reconstructing a hematopoietic system and repairing other damaged tissues. WBC, RBC and platelet counts recovered to normal after 1 month, and VDR gene expression was found in various tissues of viable VDR(-/-) recipients. Adult BM harbors pluripotent NA-MSCs, which can migrate in vivo into multiple body organs. In an appropriate microenvironment, they can adhere, proliferate and differentiate into specialized cells of target tissues and thus function in damaged tissue regeneration and repair.
