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- Abu-Zidan, Fikri M.
(författare)
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Role of platelet-activating factor in sepsis and shock : an experimantal study
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study the role of platelet-activating factor (PAF) on cardiovascular and pulmonary dysfunction in sepsis and shock.Design: Experimental study. Setting: Trauma research unit, university department of surgery, Sweden.Material: 76 juvenile domestic pigs. Interventions: The effects of a specific PAF receptor antagonist (BB-882) on haemodynamics and on PAF-induced haemodynamic changes were studied (n = 16). BB-882 was given as pretreatment in non-hypotensive Escherichia coli endotoxaemia (n = 9), during resuscitation after severe haemorrhagic shock (n = 7), hefore post-ischaemic shock which was induced by clamping the aorta above the coliac axis for 45 minutes (n = 8), and as pretreatment in post-haemorrhage septic shock: (n = 6). BB~882 groups were compared with controi groups having the same number of animals which received vehicle instead.Major outcome measures: Heart rate, intravascular pressures, cardiac output, pulmonary and systemic vascular resistance, arteriai blood gas tensions, lung thorax compliance, serum lactic acid and blood sugar concentrations, and packed cell volume.Results: BB-882 effectively counleracted the PAF-induced response on the mean systemic and pulmonary arteriai pressures. lt reduced the rise in pulmonary and systemic vascular resistance and improved the cardiac output in non-hypotensive and post-haemorrhage septic shock when given as pretreatment. lt reduced the hypertension in non-hypotensive sepsis and the hypotension in post-haemorrhage septic shock. BB-8B2 did not infiuence the endotoxin-induced hypoxia or reduced lung thorax compliance in non-hypotensive sepsis and post-haemorrhage septic shock. It did not improve the mean arterial pressure or the cardiac output in haemorrhagic shock alone but it reduced the systemic vascular resistanc'e and was associated with tachycardia and acidosis. It did not affect the post-ischaemic shock after clamping the aorta.Conclusion: PAF is a major mediator of the cardiovascular, but not pulmonary dysfunction in sepsis whether associated with shock or not, while its role on the cardiovascular dysfunction in haemorrhagic and post-ischaemic shock is small.
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- Sundberg, Christian, et al.
(författare)
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Tumor cell and connective tissue cell interactions in human colorectal adenocarcinoma : Transfer of platelet-derived growth factor-AB/BB to stromal cells
- 1997
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Ingår i: American Journal of Pathology. - 0002-9440 .- 1525-2191. ; 151:2, s. 479-492
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms underlying stimulation of platelet-derived growth factor (PDGF) beta-receptors expressed on connective tissue cells in human colorectal adenocarcinoma were investigated in this study. PDGF-AB/BB, but not PDGF receptors, was expressed by tumor cells in situ, as well as in tumor cell isolates of low passage from human colorectal adenocarcinoma. In an experimental co-culture system, conditioned medium from tumor cells only marginally activated PDGF beta-receptors expressed on fibroblasts. In contrast, co-culturing of the two cell types led to a marked PDGF beta-receptor activation. Functional PDGF-AB/BB was found to be associated with heparinase-I-sensitive components on the tumor cell surface. PDGF-AB/BB, isolated from heparinase-I-sensitive cell surface components, induced a marked activation of PDGF beta-receptors. Furthermore, co-culturing tumor cells together with fibroblasts led to a sustained activation of PDGF beta-receptors expressed on fibroblasts. Double immunofluorescence staining of tissue sections from human colorectal adenocarcinoma, combined with computer-aided image analysis, revealed that nonproliferating tumor cells were the predominant cellular source of PDGF-AB/BB in the tumor stroma. In addition, PDGF-AB/BB-expressing tumor cells were found juxtapositioned to microvascular cells expressing activated PDGF beta-receptors. Confocal microscopy revealed a cytoplasmic and cell-membrane-associated expression of PDGF-AB/BB in tumor cells situated in the stroma. In contrast, epithelial cells situated in normal or tumorous acinar structures revealed only a cell-membrane-associated PDGF-AB/BB expression. The is vitro and in situ results demonstrate that tumor cells not only facilitate but also have the ability to modulate connective tissue cell responsiveness to PDGF-AB/BB in a paracrine fashion, through direct cell-cell interactions in human colorectal adenocarcinoma.
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