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American Journal of Ophthalmology Case... Jun 2020
PubMed: 32322747
DOI: 10.1016/j.ajoc.2020.100677 -
British Journal of Pharmacology Mar 2018The kinin B receptor contributes to vascular inflammation and blood-retinal barrier breakdown in diabetic retinopathy (DR). We investigated the changes in expression,...
BACKGROUND AND PURPOSE
The kinin B receptor contributes to vascular inflammation and blood-retinal barrier breakdown in diabetic retinopathy (DR). We investigated the changes in expression, cellular localization and vascular inflammatory effect of B receptors in retina of streptozotocin diabetic rats.
EXPERIMENTAL APPROACH
The distribution of B receptors on retinal cell types was investigated by immunocytochemistry. Effects of B receptor agonist, R-838, and antagonist, R-954, on retinal leukocyte adhesion, gene expression of kinin and VEGF systems, B receptor immunoreactivity, microgliosis and capillary leakage were measured. Effect of B receptor siRNA on gene expression was also assessed.
KEY RESULTS
mRNA levels of the kinin and VEGF systems were significantly enhanced at 2 weeks in streptozotocin (STZ)-retina compared to control-retina and were further increased at 6 weeks. B receptor mRNA levels remained increased at 6 months. B receptor immunolabelling was detected in vascular layers of the retina, on glial and ganglion cells. Intravitreal R-838 amplified B and B receptor gene expression, B receptor levels (immunodetection), leukostasis and vascular permeability at 2 weeks in STZ-retina. Topical application (eye drops) of R-954 reversed these increases in B receptors, leukostasis and vascular permeability. Intravitreal B receptor siRNA inhibited gene expression of kinin and VEGF systems in STZ-retina. Microgliosis was unaffected by R-838 or R-954 in STZ-retina.
CONCLUSION AND IMPLICATIONS
Our results support the detrimental role of B receptors on endothelial and glial cells in acute and advanced phases of DR. Topical application of the B receptor antagonist R-954 seems a feasible therapeutic approach for the treatment of DR.
Topics: Administration, Ophthalmic; Animals; Bradykinin; Capillary Permeability; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Gene Expression Regulation; Leukostasis; Male; RNA, Messenger; RNA, Small Interfering; Rats; Rats, Wistar; Receptor, Bradykinin B1; Retina; Streptozocin
PubMed: 29285756
DOI: 10.1111/bph.14138 -
Annals of Hematology Apr 2023Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a...
Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a strategy to reduce this risk, and the initial management of these patients remains heterogeneous worldwide. The aim of the present study was to evaluate the influence of a short course of intravenous dexamethasone on the early outcomes of patients with hyperleukocytic AML with white blood cell (WBC) count above 50 × 10/L. Clinical and biological data of all consecutive patients (1997-2017) eligible for intensive chemotherapy from a single center were retrospectively collected. A total of 251 patients with a median age of 51 years and a median WBC count of 120 × 10/L were included, 95 of whom received dexamethasone. Patients treated with dexamethasone had higher WBC count and a more severe disease compared with those who did not, and they presented more often with leukostasis and hypoxemia, resulting in a more frequent need for life-sustaining therapies (p < 0.001). To account for these imbalances, patients were compared after adjusting for a propensity score, which included all variables with a prognostic influence in the overall cohort. In the matched cohort, dexamethasone was associated with lower early death (OR = 0.34, p = 0.0026) and induction failure rate (OR = 0.44, p = 0.02) and better overall survival (HR = 0.60, p = 0.011), with no impact on relapse risk (cHR = 0.73, p = 0.39). The overall survival benefit was confirmed among all tested subgroups. This study suggests that dexamethasone administration is safe and associated with a lower risk of induction mortality in patients with hyperleukocytic AML and deserves prospective evaluation.
Topics: Humans; Middle Aged; Leukocytosis; Propensity Score; Retrospective Studies; Leukemia, Myeloid, Acute; Dexamethasone
PubMed: 36773040
DOI: 10.1007/s00277-023-05119-3 -
Scientific Reports Dec 2016The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized...
The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases.
Topics: 8,11,14-Eicosatrienoic Acid; Adamantane; Animals; Cells, Cultured; Disease Models, Animal; Down-Regulation; Endothelial Cells; Epoxy Compounds; Fatty Acids, Unsaturated; Humans; Intercellular Adhesion Molecule-1; Lauric Acids; Male; Mice; Retinal Vasculitis; Retinal Vessels; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1
PubMed: 27966642
DOI: 10.1038/srep39211 -
Frontiers in Pediatrics 2023Leukapheresis reduces hyperleukocytosis in children with acute leukemia. Although the usefulness of this procedure is under debate, a repeated small-volume exchange...
INTRODUCTION
Leukapheresis reduces hyperleukocytosis in children with acute leukemia. Although the usefulness of this procedure is under debate, a repeated small-volume exchange transfusion along with leukapheresis yielded satisfactory results.
METHODS
Forty-seven patients with acute leukemia [32 acute lymphocytic leukemia (ALL) and 15 acute myeloblastic leukemia (AML)] were enrolled between January 2017 and June 2022 and underwent repeated small-volume exchange transfusion. The following were measured: demographic and clinical characteristics, time of the procedure, PWBC (peripheral white blood cell) count, hemoglobin, platelet count, blood biochemistry, electrolytes, coagulation, leukostasis, TLS (tumor lysis syndrome), DIC (disseminated intravascular coagulopathy), adverse events (AEs), and serious AEs (SAEs).
RESULTS
The demographic and clinical characteristics were not significantly different between ALL and AML patients, but differences were observed in PWBC counts (424.2 ± 135.6 vs. 223.8 ± 58.0 × 109/L). The procedures needed 3-8 processes, and the average procedure time was not significantly different between ALL and AML. The PWBC count gradually reduced to <100 × 109/L; hemoglobin, platelet count, K+, Na+, and Ca2+ were unchanged. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, troponin-I, creatine kinase-MB, prothrombin time, and activated partial thromboplastin time maintained normal or recovered from abnormal ranges. The manifestations of leukostasis, TLS, and DIC improved or disappeared. No AEs and SAEs occurred. The required total blood volume was based on initial PWBC count, manifestations of leukostasis, and age.
CONCLUSIONS
Our finding suggests that repeated small-volume exchange transfusion is effective and safe for treating hyperleukocytosis in children with acute leukemia.
PubMed: 37033185
DOI: 10.3389/fped.2023.1155481 -
Transfusion Medicine and Hemotherapy :... Aug 2022Leukostasis refers to clinical symptoms caused by hyperleukocytosis seen in some haematological diseases such as leukaemia. Cytoreduction can be achieved by therapeutic...
INTRODUCTION
Leukostasis refers to clinical symptoms caused by hyperleukocytosis seen in some haematological diseases such as leukaemia. Cytoreduction can be achieved by therapeutic leukapheresis. The aim of this study was to retrospectively analyse the procedures performed in our Centre and to evaluate their efficacy and safety.
METHODS
This was a retrospective study of all the therapeutic leukapheresis procedures carried out in our Centre between January 1998 and December 2020. The sample collection was obtained through the review of the clinical files of the respective patients. Statistical analysis was performed using the software R v.4.0.1. A total of 54 therapeutic leukapheresis procedures were performed in 31 patients in our Centre.
RESULTS
After these procedures clinical improvement was observed in 16 patients and we verify that there was a significant difference in survival between the group that improved and the group that maintained the same clinical condition or worsened. The lack of immediate clinical improvement was a sign of a poor prognosis. Laboratory efficacy occurred in 16 patients who had a reduction in white blood cell count, with a 39.1% reduction after 24 h, and did not succeed in 15 patients, who had no reduction. However, in this case there is no significant difference in survival between the two groups. There was some complication in 53.9% of the procedures, with hypocalcaemia being the most frequent, which was observed in 22 procedures. Only 4 patients experienced serious side effects but these adverse reactions cannot be attributed to the procedures carried out. The overall survival rate 6 months after this treatment was 51.6%.
CONCLUSION
Despite the reduced number of patients, we conclude that therapeutic leukapheresis is a safe and effective option that may still have a therapeutic role in some cases.
PubMed: 36159955
DOI: 10.1159/000520933 -
International Journal of Molecular... Jun 2020We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and...
Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model.
We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8-18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood-retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1β in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1b, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1β receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation.
Topics: Animals; Blood-Retinal Barrier; Capillary Permeability; Carrier Proteins; Caspase 1; Cell Adhesion Molecules; Coculture Techniques; Diet, High-Fat; Disease Models, Animal; Endothelial Cells; Female; Gene Deletion; Humans; Inflammasomes; Inflammation; Insulin Resistance; Interleukin-1beta; Leukostasis; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Retina; Thioredoxins
PubMed: 32492941
DOI: 10.3390/ijms21113983 -
Cureus Nov 2021Acute coronary syndrome (ACS) is a condition that develops from reduced blood flow and oxygen delivery through the coronary arteries which leads to cardiac ischemia. In...
Acute coronary syndrome (ACS) is a condition that develops from reduced blood flow and oxygen delivery through the coronary arteries which leads to cardiac ischemia. In the case presented here, the patient's ACS was precipitated by his underlying condition of chronic myelogenous leukemia (CML). Several complications can arise in patients with CML, one of them being blast crisis. Blast crisis is defined by 20% or greater blasts in the peripheral blood, or extramedullary proliferation of blasts.There is a known phenomenon of blood hyperviscosity that can develop in such patients which can lead to complications of stroke-like symptoms, congestive heart failure, and acute respiratory failure. In such cases, leukostasis rarely leads to myocardial ischemia. We present a challenging case of a patient with an acute coronary syndrome (ACS) precipitated by a blast crisis. This case highlights a potentially life-threatening cardiac complication of CML in patients with coronary artery disease and aimed to provide an optimal treatment strategy to improve outcomes.
PubMed: 34926059
DOI: 10.7759/cureus.19589 -
Nefrologia : Publicacion Oficial de La... Nov 2014
Topics: Acrylic Resins; Acrylonitrile; Anaphylatoxins; Anaphylaxis; Complement Activation; Fluorocarbons; Humans; Hypersensitivity, Immediate; Incidence; Leukostasis; Membranes, Artificial; Polymers; Prevalence; Renal Dialysis; Spain; Sulfones
PubMed: 25415569
DOI: 10.3265/Nefrologia.pre2014.Jul.12682 -
Cureus Dec 2023Acute myeloid leukemia (AML), the most common form of acute leukemia, is an aggressive lethal hematological malignancy that mainly occurs in older adults with a slightly...
Acute myeloid leukemia (AML), the most common form of acute leukemia, is an aggressive lethal hematological malignancy that mainly occurs in older adults with a slightly higher predominance in males. It is prompted by the clonal expansion of immature myeloid blasts in the bone marrow, peripheral blood, and/or extramedullary tissues. Leukostasis in AML is a critical medical condition mainly affecting the lungs and brain and arises when tissue perfusion is compromised due to the clustering of white blood cells (WBCs) within the microvasculature. Cardiac involvement in this condition is exceptionally uncommon. Here, we present a case of a 56-year-old man, recently diagnosed with acute myelogenous leukemia M4 and leukostasis, who developed acute anterior ST-elevation myocardial infarction six days after presentation and in whom emergent coronary angiography showed proximal left anterior descending (LAD) artery lesion with a large clot obstructing the flow and thrombolysis in myocardial infarction (TIMI) I flow, and urgent percutaneous coronary intervention (PCI) was done; thromboaspiration and drug-coated balloon angioplasty were performed with good angiographic results. Antiplatelet (aspirin and clopidogrel) and anticoagulation (enoxaparin) were started immediately before PCI. Emergent leukapheresis was initiated in addition to hydroxyurea with complete resolution of chest pain. Four days post PCI, the patient developed right-sided hemiparesis with an evident infarct on a CT scan of the brain, and he also developed acute limb ischemia involving the distal right foot. Five days post PCI, the patient had a sudden sustained ventricular tachycardia followed immediately by asystole, and cardio-pulmonary resuscitation was done for 25 minutes but with no response.
PubMed: 38077674
DOI: 10.7759/cureus.50230