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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study attempts to determine whether the circulating neutrophils play a role in mediating injury resulting from renal ischemia, using rats treated with cyclophosphamide (CY) and/or granulocyte colony-stimulating factor (G-CSF). The neutrophil counts immediately before 60-minute ischemia decreased by 89% in the CY-treated rats in comparison with the untreated animals (p < 0.01). In the rats given G-CSF with CY, the neutrophil counts significantly increased over that of the CY-treated rats (p < 0.01). The serum creatinine level 24 hours after reperfusion amounted to 4.42 +/- 0.37 mg/dl in the control rats and 2.63 +/- 0.29 mg/dl in the CY-treated rats (p < 0.01). In 19 rats, 10 controls and the 9 CY-treated, the neutrophil counts immediately before ischemia correlated well with the serum creatinine levels 24 hours after reperfusion (r = 0.597; p < 0.01). Our results appear to indicate that neutrophils play an important role in warm ischemia and reperfusion injury of the kidney.
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PMID:[Role of neutrophils in warm renal ischemia and reperfusion injury in the rat]. 751 83

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that regulates the proliferation and maturation of hematopoietic progenitor cells and modulates the function of mature neutrophils. The responses to administration of G-CSF alone, and in combination with antimicrobials, were studied in an equine model of ascending colon ischemia. Complete segmental colonic ischemia (3.75 hours) with pelvic flexure enterotomy was created in four treatment groups. Group 1 horses received recombinant canine G-CSF (10 micrograms/kg, every 24 hours, intramuscularly), gentamicin sulfate (2.2 mg/kg, every 8 hours, intravenously), and potassium penicillin G (40,000 IU/kg, every 6 hours, intravenously). Group 2 horses were treated with the G-CSF vehicle and antimicrobials as for group 1. Group 3 horses received G-CSF and the antimicrobial drug vehicles, and group 4 horses served as the untreated control receiving G-CSF vehicle and antimicrobial vehicles. The results for 20 horses, five horses in each group, were compared. Treatment with G-CSF was associated with an increased concentration of white blood cells, band neutrophils, neutrophils, lymphocytes, and monocytes in the peripheral blood after surgery. Antimicrobial administration had no detectable effect on cell concentrations after surgery. Administration of G-CSF was associated with an increased concentration of nucleated cells in the peritoneal fluid including neutrophils, small mononuclear cells and large mononuclear cells. Horses that developed incisional infections had lower neutrophil concentrations in the peripheral blood on postoperative day 2 than horses without infected incisions. These results suggested that the prophylactic administration of G-CSF may be useful in the treatment of patients at risk for developing neutropenia after surgery.
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PMID:Effects of perioperative granulocyte colony-stimulating factor on horses with ascending colonic ischemia. 769 19

Granulocyte colony-stimulating factor (G-CSF) is the cytokine that is critical for polymorphonuclear neutrophilic granulocyte (PMN) production as well as being a potent agonist of PMN activation. We have recently reported that in the lung and the liver of rats resuscitated after hemorrhagic shock (HS) G-CSF mRNA expression is induced. It is not known if both phases of HS, the ischemic and the reperfusion phase, are required for G-CSF mRNA induction. The present study was designed to test the hypothesis that the upregulation of G-CSF mRNA expression is the consequence of HS followed by resuscitation and that ischemia alone is insufficient to induce G-CSF mRNA expression in the affected organs. Male Sprague-Dawley rats were subjected to resuscitated and unresuscitated shock protocols of varying severity. Control animals were subjected to anesthesia and all surgical preparations except for hemorrhage. Lungs and livers were isolated and their RNA extracted. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that G-CSF mRNA was induced in the lung and liver of shock animals above the level observed in control animals. Upregulation of G-CSF mRNA relative to controls occurred only in animals undergoing resuscitated HS and not in ones subjected to unresuscitated HS. These results indicate that G-CSF production specific for the hemorrhage component of shock is dependent on resuscitation. As a consequence, the production of this cytokine may be decreased through modifications in the resuscitation protocols.
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PMID:Granulocyte colony-stimulating factor (G-CSF) production in hemorrhagic shock requires both the ischemic and resuscitation phase. 906 Nov 73

Optimal medical treatment of ischemic diabetic ulcers is multifactorial. Infection is very common and it is necessary to distinguish between limb or life threatening infections and non-limb-threatening infections. The major pathogen associated with non-limb-threatening infection is staphylococcus aureus; oral antibiotics such as amoxicillin/clavulanate or clindamycin can be used. For severe infection, empiric antibiotic therapy is broader-spectrum covering staphylococci, streptococci, gram-negative bacilli and enterococci; intravenous administration is the rule. Duration of antibiotic therapy depends on severity and depth of infection, and on requirement of surgical debridment. Granulocyte colony-stimulating factor is a growth factor stimulating proliferation and function of neutrophils. As an adjunctive therapy for limb-threatening infections, it is associated with a lower rate of amputation. Increasing arterial perfusion if the patient is unsuitable for reconstructive surgery or angioplasty is desirable. Iloprost is an analogue of epoprostenol with effects on platelet aggregability and vasodilatation. It improves ulcer healing, decreases pain, slightly diminishes the rate of amputation. Systemic hyperbaric oxygen therapy can perhaps improve clinical outcome but additional research is needed to define the specific indications and benefits of this treatment modality. Local care is not rationalized and depends on local habits. Debridment is required. Non necrotic wounds can be covered by modern dressing (hydrophilic dressing, alginates, hydrocolloid). Necrotic wounds are dryed until surgical revascularization, or excised if they are limited and superficial. Pinch grafts are very useful for arterial ulcers. The place of topical growth factor like PDGF (platelet derived growth factor) and of living skin equivalents (dermagraft, apligraf) is not defined in ischaemic diabetic ulcers. Treatment of edema is necessary, because it retards or complicates healing. Inelastic bandages can be useful with good tolerance if ischemia is not critical. Pneumatic foot compression is under evaluation. Electric stimulation could be an adjuncting treatment, but with a problem of compliance. Reducing plantar pressure is always necessary.
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PMID:[Local care and medical treatment for ischemic diabetic ulcers]. 1223 32

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

Adult marrow-derived cells have been shown to contribute to various nonhematologic tissues and, conversely, primitive cells isolated from nonhematopoietic tissues have been shown to reconstitute hematopoiesis. Circulating endothelial progenitor cells (EPCs) have been reported to be at least partially donor derived after allogeneic bone marrow transplantation, and shown to contribute to neovascularization in murine ischemia models. However, it is unknown whether these EPCs are actually clonally derived from the same population of stem and progenitor cells that reconstitute hematopoiesis, or from another cell population found in the marrow or mobilized blood that is transferred during transplantation. To approach this question, we characterized circulating EPCs and also endothelial cells from large vessels harvested at autopsy from rhesus macaques previously transplanted with retrovirally transduced autologous CD34-enriched peripheral blood stem cells (PBSCs). Endothelial cells were grown in culture for 21-28 days and were characterized as CD31(+) CD14(-) via flow cytometry, as acLDL(+) UEA-1(+) via immunohistochemistry, and as Flk-1(+) by reverse transcriptase-polymerase chain reaction (RT-PCR). Animals had stable vector marking in hematopoietic lineages of 2-15%. Neither cultured circulating EPCs collected in steady state (n = 3), nor endothelial cells grown from large vessels (n = 2), had detectable retroviral marking. EPCs were CD34(+) and could be mobilized into the circulation with granulocyte colony-stimulating factor. Under ex vivo culture conditions, in which CD34(+) cells were optimized to transduce hematopoietic progenitor and stem cells, there was a marked depletion of EPCs. Transduction of EPCs was much more efficient under conditions supporting endothelial cell growth. Further elucidation of the origin and in vivo behavior of EPCs may be possible, using optimized transduction conditions and a vascular injury model.
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PMID:Analysis of origin and optimization of expansion and transduction of circulating peripheral blood endothelial progenitor cells in the rhesus macaque model. 1248 99

Ischemic acute renal failure involves not only the kidney but also extrarenal organs such as the bone marrow that produces inflammatory cells. By ELISA and RNase protection assays, we now show that renal ischemia-reperfusion increases serum concentrations of granulocyte macrophage colony-stimulating factor (G-CSF) protein and increases both G-CSF mRNA and protein in the ischemic kidney. In situ hybridization localized the increased G-CSF mRNA to tubule cells, including medullary thick ascending limb cells (mTAL), in the outer medulla. We also show that mTAL produce G-CSF protein and increase G-CSF mRNA after stimulation by reactive oxygen species in vitro. The production of G-CSF by the kidney after ischemia-reperfusion provides a means of communication from the injured kidney to the bone marrow. This supports the known inflammatory response to ischemia.
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PMID:Ischemia-reperfusion induces G-CSF gene expression by renal medullary thick ascending limb cells in vivo and in vitro. 1473 60

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 micro g/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient's limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in ankle-brachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angio-graphic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.
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PMID:Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. 1498 38

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with neuroprotective and antiinflammatory properties. By real-time polymerase chain reaction we show that G-CSF transcripts are induced 485-fold at 4 h and 65-fold at 16 h in ischemic lesions after middle cerebral artery occlusion compared to control brains. Further analysis in photochemically induced focal ischemia revealed that G-CSF induction involved both the infarct area and remote nonischemic brain regions. Remote responses could be blocked by the noncompetitive NMDA receptor antagonist MK-801, suggesting periinfarct depolarizations as a trigger. To further confirm this notion, cortical spreading depression (CSD) was induced by focal application of KCl to the brain surface. CSD led to a 90-fold increase in G-CSF mRNA. Contrastingly, the induction of granulocyte-monocyte (GM)-CSF, another member of the hematopoietic growth factor family, was only moderate (sixfold) and restricted to ischemic brain lesions. In conclusion, G-CSF induction in the brain may be part of an intrinsic stress response aimed at limitation of neuronal damage.
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PMID:Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression. 1553 Jun 54

Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability of hematopoietic stem cells, induced by stem cell factor and granulocyte colony-stimulating factor, to the injured kidney provides an adequate strategy for stem cell-based therapy to counteract renal ischemia/reperfusion injury. It is interesting that cytokine treatment before injury resulted in significant enhancement of function recovery of the kidney. This, however, was not due to increased incorporation of tubular epithelial cells from bone marrow origin. Importantly, cytokine treatment resulted in impaired influx of granulocytes into the injured kidney. Although cytokine treatment improved renal function rapidly after ischemic injury, the results show that the underlying mechanism likely is not based on stem cell transdifferentiation but rather on altered inflammatory kinetics.
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PMID:Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution. 1582 14


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