19 research outputs found
Glomerular platelet-activating factor levels and origin in experimental glomerulonephritis
Glomerular platelet-activating factor levels and origin in experimental glomerulonephritis. The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed following extraction, isolation and quantification of this alkyl ether lipid using a bioassay based on [3H]-serotonin release from labelled rabbit platelets. Following induction of NSGN using proteinuric doses of rabbit immune serum raised against rat glomerular basement membrane, enhanced glomerular PAF levels were observed at 3 hours, 24 hours and on day 15 following induction of the disease. In complement depleted rats and at three hours following induction of NSGN, glomerular PAF levels were significantly lower than in complement replete controls studied in parallel. At the same time point of the disease, platelet depleted rats with NSGN demonstrated significantly lower glomerular PAF levels than parallel controls, whereas in neutrophil depleted rats glomerular PAF levels were no different than controls. These observations indicate that in infiltrative and complement dependent forms of glomerular immune injury, glomerular PAF levels are increased via a complement mediated mechanism. Infiltrating platelets, but not neutrophils, partially account for the enhanced glomerular PAF levels. The observations are of potential importance in the pathophysiology of glomerulonephritis
Glomerular platelet activating factor (PAF) levels and origin in experimental glomerulonephritis
The renal glomerulus and its various cell types (i.e. mesangial cells, endothelial cells) have been shown to synthesize compounds with autacoid and proinflammatory effects. [97,98] The spectrum of proinflammatory compounds of glomerular origin has recently expanded to include the alkyl ether glycerophospholipids, including 1-O-alkyl-2- acetyl-sn- glycero-3- phosphorylcholine, which is structurally identical with platelet activating factor (PAF).This compound can induce platelet and neutrophil aggregation and chemokinesis, vasodilation, increased vascular permeability and stimulation of eicosanoid production. We have demonstrated that PAF can be both synthesized and degraded in isolated glomeruli and in mesangial cells, [7,99] the latter being also capable of de novo synthesis of PAF precursors. Recent observations indicate that PAF receptor antagonism ameliorates glomerular inflammation in rabbit nephrotoxic serum nephritis, as well as the glomerular inflammatory injury induced by in situ formation of immune complexes in the rat kidney with experimental passive reverse Arthus reaction. [100,101] The present study was undertaken in order to assess the levels and cellular sources of glomerular PAF in glomeruli isolated from rats with: 1) Nephrotoxic serum nephritis, an infiltrative and complement dependent model of immune injury and 2) passive Heymann nephritis a non- infiltrative but complement dependent model. The role of complement, platelets and polymorphonuclear leucocytes was assessed. The observation that mesangial cells is the main source of PAF production in the rat glomerulus, prompted the assessment of the effect of various inflammatory mediators on the acetyl-transferase activity of the mesangial cells. […
The biological activity of acetylated sphingosylphosphorylcholine derivatives
Taking into account their stereochemical similarity with
1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine (PAF), which is known
to exhibit a diverse spectrum of biological actions, including platelet
aggregating and glycogenolytic activity, the acetylated derivatives of
sphingosylphosphorylcholine and sphingomyelin were synthesized and
tested for their ability to promote washed rabbit platelet aggregation
and glycogenolysis in Tetrahymena pyriformis cells. Sphingomyelin (SPM)
and sphingosylphosphorylcholine (SPC) were subjected to acetylation,
following chromatographic purification and physicochemical
characterization. The synthesized compounds N-acetyl, O-acetyl SPC (NAc,
OAc SPC), N-acetyl SPC (NAc SPC) and O-acetyl SPM (OAc, SPM) were tested
far their biological activity in the washed rabbit platelets and washed
Tetrahymena pyriformis cell systems. These derivatives induced [H-3]
serotonin and ATP release and a monophasic aggregation of washed rabbit
platelets in the concentration range 10(-8)-10(-6) M, However, authentic
PAF-induced washed rabbit platelet aggregation was inhibited at higher
concentrations of the acetylated sphingophospholipid compounds (> 10(-6)
M) and by the PAF-specific receptor(s) antagonists kadsurenone and
triazolam. Platelet desensitization and crossed desensitization
experiments with authentic PAF and the acetylated sphingophospholipids,
suggested interaction with the same receptor(s) as PAF and different
from the ADP or thrombin receptor. The involvement of calmodulin and
protein kinase C in the biological activity of the prepared analogues
was also demonstrated. Besides their action on rabbit platelets, the
PAF-like activity of the acetylated sphingophospholipids was also
demonstrated in a platelet-independent system, by showing that they
stimulate glycogenolysis in washed Tetrahymena pyriformis cells. These
observations indicate that a new class of compounds with PAF-like
activity were synthesized, but their role in the cellular metabolism
remains to be shown. The existence of acetylated sphingophospholipids
with PAF-like activity has so far been reported only in Urtica dioica
Positive Tc-99m-MIBI scan in a patient with confirmed Paget's disease of bone
A 46-year-old man was referred to our department for a Tc-99m MDP bone
scan after he was admitted to our hospital with diffuse bone pain and
the subsequent finding of multiple mixed type (lytic-blastic) lesions on
routine x-rays. The Tc-99m MDP scan was highly suspicious for malignancy
and, therefore, a Tc-99m MIBI scan was performed, which also revealed
abnormal uptake in all regions with increased osteoblastic activity.
Clinical chemistry and further workup revealed a highly elevated serum
alkaline phosphatase and increased excretion of hydroxyproline in the
urine. The presumed diagnosis of Paget’s disease of the bone was further
confirmed by biopsy