44,356 research outputs found
Arachidonic acid metabolism in inflammatory cells of patients with bronchial asthma
Over the last few years, the demonstration of bene®cial effects of leukotriene
receptor antagonists in various forms of asthma has renewed clinical and
pharmacologic interest in this class of lipid mediators. Several studies
demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in
asthmatic patients. However, the reasons for the dysregulated production of
CysLTs in asthmatic patients are not completely de®ned. An improved method
of lipid mediator detection and the availability of cells isolated from human
airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed
initial studies to address this issue. Eosinophils retrieved from in ̄amed airways
of asthmatics have a larger arachidonic acid (AA) content than their blood
counterpart. The high level of AA in these cells is primarily due to a remodeling
of endogenous arachidonate pools with the accumulation of this fatty acid in a
triglyceride-associated pool. In addition, elevated levels of a secretory form of
phospholipase A2, the key enzyme initiating the cascade of CysLTs, are found in
the BAL of asthmatics. Finally, eosinophils isolated from the BAL of asthmatics
have an increased expression of LTC4 synthase. The level of expression of this
enzyme correlates with the increased amount of CysLTs produced in the airways
of these patients. Taken together, these data identify at least two possible
mechanisms to explain the excessive CysLT production in asthmatics:
1) an increased content of AA in the glycerolipid pools of in ̄ammatory
cells
2) an enhanced activity of key biosynthetic enzymes involved in CysLT
synthesis
The apparent friction of granular fault gouge in sheared layers
Data are presented from a series of experiments on layers of granular quartz gouge in the double-direct-shear geometry at a normal stress of 25 MPa. The apparent friction of a layer shows considerable variability depending on the thickness of the layer and the particle size distribution of the gouge. Measurements of layer thickness during the experiments also show that the layers thin as shearing proceeds. When densification is also admitted, a simple flow law with one adjustable parameter is required to relate the volumetric and shear strain rates. -from Author
Erythropoietin production in the rat: additive role of kidney and liver.
Erythropoietin (Ep) levels were evaluated in serum of neonate, weanling, or adult rats subjected to 1) sham operation, nephrectomy, and/or subtotal hepatectomy and 2) a standard bout of hypoxia (0.45 atm air/6 h, starting 1 h after the operation). Ep activity was quantitated by means of strictly controlled assays in exhypoxic polycythemic mice. The sum of Ep titers in the serum of nephrectomized or hepatectomized rats was compared to Ep levels in sham-operated animals of corresponding age levels, with the exception of 1-wk-old rats: it is relevance that no significant difference is apparent between these Ep production curves. Thus, evidence is presented indicating for the first time that Ep derives from two functionally distinct and additive sources, i.e., the kidney and the liver. Liver Ep, although prevalent in neonatal animals, is obscured in the weanling adult rat by both gradual initiation of massive renal Ep production and progressive decrease of hepatic Ep activity. </jats:p
Immunopathogenesis of psoriasis and psoriatic arthritis and pharmacological perspectives
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