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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Severe traumatic brain injury stimulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) into CSF. Studies in cultured mouse astrocytes suggest that sICAM-1 induces the production of macrophage inflammatory protein-2 (MIP-2). In the present study, we investigated the underlying mechanisms for MIP-2 induction. sICAM-1 induced MIP-2 in astrocytes lacking membrane-bound ICAM-1, indicating that its action is due to heterophilic binding to an undescribed receptor rather than homophilic binding to surface ICAM-1. Signal transduction may be mediated by src tyrosine kinases, as the src tyrosine kinase inhibitors herbimycin A and PP2 abolished MIP-2 induction by sICAM-1. Phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), but not of p38 MAPK, occurred further downstream, as evidenced by western blot analysis combined with the use of herbimycin A and specific MAPK inhibitors. By contrast, induction of MIP-2 by tumour necrosis factor-α (TNF-α) involved both p42/44 MAPK and p38 MAPK. Following stimulation with either sICAM-1 or TNF-α, astrocyte supernatants promoted chemotaxis of human neutrophils and incubation of these supernatants with anti-MIP-2 antibodies more efficiently suppressed the migration induced by sICAM-1 than by TNF-α. These results show that sICAM-1 induces the production of biologically active MIP-2 in astrocytes by heterophilic binding to an undefined receptor and activation of src tyrosine kinases and p42/44 MAPK.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Cold storage, rat liver, microcirculation ; Microcirculation, rat liver ; Euro-Collins, microcirculation, rat liver ; UW, microcirculation, rat liver ; HTK, microcirculation, rat liver ; Transplantation rat liver, micro-circulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 μmol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3±0.2 μm; mean±SEM) compared with the UW group (9.5±0.2 μm; P〈0.05) and HTK group (10.2±0.8 μm; P〈0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5±1%), while this phenomenon was less pronounced in the UW group (14.5+1.1%; P〈0.05) and HTK group (16.3±0.7%; P〈0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7+1.3%) compared with the UW group (30.5+2.1%) and the HTK group (34.4+0.8%). Microcirculatory failure and cell swelling in the EC group might be due to the lack of osmotic substances or oxygen radical scavengers included in UW (allopurinol, glutathione) and HTK (mannitol) solutions. In conclusion, cold storage of livers in UW and HTK solutions results in better preservation of the microcirculation and prevention of adhesion of leucocytes after transplantation compared with the EC solution.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1615-3146
    Keywords: Key Words Multiple injury ; Pelvic injury ; Hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The combination of multiple injuries and pelvic ring disruption often represents a devastating injury pattern. This study evaluates therapeutical strategies and the outcome of 174 severely traumatized patients with pelvic ring injury (ISS: 32.1±11.1 patients) over a 6-year period. Patients were divided into 3 groups according to their hemodynamic status at admission. Forty-one patients in extremis (group A; ISS: 40.1±11.1 patients) which required the highest resuscitation efforts revealed a mortality rate of 90%. Many of these patients underwent crash laparotomy (44%)/thoracotomy (22%), aortic clamping (22%), and pelvic packing (44%). Patients with persistent hemodynamic instability (group B; n = 39; ISS: 34.2±9.6 patients) had a mortality rate of 26% (p〈0.05 versus group A) with 14 patients (36%) undergoing emergency laparotomy. Mortality rate (5%) markedly (p〈0.05) decreased in patients with stable hemodynamics despite a relatively high ISS (group C; n = 94; ISS: 27.6±9.4 patients). Hemorrhage could be controlled in all patients of group B and C, while 23 out of 41 patients (56%) in extremis died due to exsanguination during the first 24 hours after injury. Thus, treatment of patients in extremis must be focused on aggressive resuscitation and surgical intervention without extensive diagnostic procedures to effectively control lethal hemorrhage.
    Type of Medium: Electronic Resource
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