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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have used the carrageenan-induced pouch-granuloma in rats to investigate how changes in low-molecular-mass iron chelate levels in the exudate, induced by iron loading (iron-dextran) or chelation (desferrioxamine) influence cellular and systemic inflammatory parameters. In the iron-treated group we observed a rapid decrease in the number of leukocytes and exudate volume; there was also an increase in ferritin iron and low-molecular-mass iron chelates, and on the eighth day a systemic response. In the desferrioxamine-treated group we detected a decrease in low-molecular-mass iron chelates, ferritin iron, and an increase in the number of leukocytes. We describe the protective effects of desferrioxamine against the deleterious effects of ferrous iron and relate this to its chelating and scavenging activity. The results suggest that the levels of low-molecular-mass iron chelates modulate the inflammatory response, possibly through their contribution to the oxygen free radical generation, which is responsible for the cell membrane damage and subsequently its death. The modulatory action of iron-dextran and desferrioxamine support our hypothesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Keywords: pH ; Strong ion difference ; Weak acid buffers ; Inorganic phosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interactions between the acid-base variables that contribute to exudate acidosis were studied in the subcutaneous air-pouch after carrageenan injection in rats. We studied the concurrent changes of exudate gases (P CO2 and PO2), main ions ([Na+], [K+], [Ca2+], [Mg2+], [Cl−] and [Lac−]), inorganic phosphate (Pi) and albumin in acutely inflamed rats (4, 8, 12, 24 and 48 h of inflammation). A notable hypercapnia was found in the exudate after only 8 h (exudate PCO2=64.3±2.9 mm Hg) but this hypercapnia decreased after 48 h (32.9±12.7 mm Hg), coincident with the greatest increase in exudate cells. With respect to the metabolic acid-base variables, the most important changes found were a parallel decrease in the strong ion difference ([SID]) and exudate pH, as well as increases in the exudate weak acid buffers ([ATOT]) due to albumin and inorganic phosphate (Pi) increases. However, after 12 h, the exudate acidosis was stable at around pH 7. A similar acid pH was obtained after 24 h of inflammation when the carrageenan solution injected was previously adjusted to a physiological pH (7.4). This pH, analogous to that of the exudate, was the result of compensation by the acid-base independent variables, a fact which suggests that acid pH may be a beneficial condition for cells taking part in inflammatory processes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Whole blood serum (WBS) and platelet-poor plasma-derived serum (PDS) from the same normal subject were compared for their abilities to support human megakaryocyte (MK) colony formation. In all cases, PDS promoted the growth of a higher number (20-50%) of MK colonies than did WBS. Increasing amounts of WBS decreased the number of colonies, whereas increasing concentration of PDS had no marked effects. Crude platelet extracts or platelet secretory products from thrombin-activated platelets also elicited an inhibition of MK colony formation in a dose-dependent manner. A complete inhibition was found for a dose equivalent to 1.109 platelets/ml and a 50% inhibition in a range of 1.107-1.108 platelets/ml. These platelet products were also inhibitory for erythroid progenitor growth. Platelets from two patients with gray platelet syndrome elicited only a minor inhibition of MK growth, suggesting that the platelet alpha granule is the origin of this inhibition. When platelet extracts were acid-treated, the biological activity of the inhibitor on CFU-MK and CFU-E growth was 20-50-fold higher. In addition, a potent stimulatory activity on the growth of day 7 CFU-GM was observed. The enhancement of biological activities by acid treatment suggests that type β transforming growth factor (TGF-β) could be involved in this platelet inhibitory activity. The homogeneous native TGF-β (from 1 pg to 1 ng/ml) produced the same effects previously induced by platelet products. It totally inhibited CFU-MK growth (at a 500 pg/ml), it inhibited CFU-E growth, and it stimulated growth of day 7 CFU-GM in the presence of a colony-stimulating factor. The inhibition of CFU-MK growth was also observed on purified progenitors. In conclusion, these results suggest that TGF-β may be implicated in negative autocrine regulation of megakaryopoiesis. However, since this molecule has ubiquitous biological activities, its physiologic relevance as a normal regulator of megakaryopoiesis requires further investigation.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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