Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After 14 days' bone marrow maturation, neutrophil granulocytes reach the tissues where for 1-2 days they form the army whose phagocytic function was described by llya Metchnikoff in 1882. At that time, Paul Ehrlich was developing his neutrophil secretory theory which had less success until it returned with a vengeance in the last decade. Neutrophils are not only phagocytes. Above all they are cells that secrete bactericidal effectors and regulators (amplifiers and modulators) of the inflammatory focus. More and more sophisticated methods are being used to study phagocytosis, from the point of view both of the mechanism of chemotaxis and its role in inflammation and of the mediators of oxygen-dependent bactericidal action (superoxide anion, oxygenated water, hydroxyl radicals, myeloperoxidase, halogen ions and superoxide dismutase). In addition, the importance of oxygen-independent bactericidal mechanisms has been confirmed by the discovery of proteins such as BPI (Bactericidal Permeability Increasing Protein). Study of neutrophil dysfunction throws light on a number of neutrophil regulatory and effector mechanisms; it also proves useful in explaining the recurrent infections observed in some congenital disorders (chronic granulomatous disease, the "lazy leucocyte syndrome", the Chediak-Higashi syndrome, ichthyrosis , Job's syndrome...) or those associated with transitory neutrophil disorders (measles, severe bacterial infection...). Neutropenia induced by some antibiotics is easily demonstrated, but the interactions between these antibiotics and neutrophils are complex: phagocyte concentration of antibiotic, neutrophil inactivation of antibiotic, effect of antibiotic on microbe-leucocyte interaction such as an alteration in phagocytic and chemotactic response. The neutrophil is the first blood cell to arrive at the inflammatory focus; it is also at the centre of the response, next to the humoral mediators which both act upon it and which it itself secretes.
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PMID:[Neutrophil functions and interactions in the inflammatory reaction]. 673 54

Identification of safe, effective treatments to mitigate toxicity after extensive radiation exposure has proven challenging. Only a limited number of candidate approaches have emerged, and the U.S. Food and Drug Administration has yet to approve any agent for a mass-casualty radiation disaster. Because patients undergoing hematopoietic stem cell transplantation undergo radiation treatment that produces toxicities similar to radiation-disaster exposure, we studied patients early after such treatment to identify new approaches to this problem. Patients rapidly developed endotoxemia and reduced plasma bactericidal/permeability-increasing protein (BPI), a potent endotoxin-neutralizing protein, in association with neutropenia. We hypothesized that a treatment supplying similar endotoxin-neutralizing activity might replace the BPI deficit and mitigate radiation toxicity and tested this idea in mice. A single 7-Gy radiation dose, which killed 95% of the mice by 30 days, was followed 24 hours later by twice-daily, subcutaneous injections of the recombinant BPI fragment rBPI21 or vehicle alone for 14 or 30 days, with or without an oral fluoroquinolone antibiotic with broad-spectrum antibacterial activity, including that against endotoxin-bearing Gram-negative bacteria. Compared to either fluoroquinolone alone or vehicle plus fluoroquinolone, the combined rBPI21 plus fluoroquinolone treatment improved survival, accelerated hematopoietic recovery, and promoted expansion of stem and progenitor cells. The observed efficacy of rBPI21 plus fluoroquinolone initiated 24 hours after lethal irradiation, combined with their established favorable bioactivity and safety profiles in critically ill humans, suggests the potential clinical use of this radiation mitigation strategy and supports its further evaluation.
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PMID:Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death. 2211 33