Granulocyte-Colony Stimulating Factor Improves an Impaired Bactericidal Function in Neutrophils From STZ-Induced Diabetic Rats

Sato, Norikazu; Shimizu, Hiroyuki

doi:10.2337/diab.42.3.470

Cited by 20 publications

(14 citation statements)

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“…In this study, both CLA-DCL and L-DCL in response to formylmethonyl-leucyl-phenylalanine were decreased in neutrophils from STZ-induced diabetic rats. These results were consistent with our previous observation that the generation of O 2 Ϫ and a H 2 O 2 -MPO-Cl Ϫ system were reduced in poorly controlled diabetic patients (3, 10) and STZ-induced diabetic rats (4,9). In the present study, cytosolic sorbitol concentration was increased in diabetic neutrophils, which is in agreement with the results of Wilson's group (2, 16).…”

Section: Discussionsupporting

confidence: 83%

“…1): untreated control, epalrestat-treated control, untreated diabetic, and treated diabetic (each group n ϭ 8). Diabetes was induced by a single ip injection of 60 mg/kg BW STZ (Sigma, St. Louis, MO) dissolved in 0.1 m citric buffer (pH 4.2), as described before (9). A rat was considered diabetic if it had a nonfasting serum glucose level more than 20 mmol/liter 3 days after STZ injection.…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

“…Accordingly, drugs (e.g. granulocyte-colony stimulating factor) which improve impaired neutrophils function may prevent or decrease susceptibility to infection in diabetic patients (9,10).…”

mentioning

confidence: 99%

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Effect of Epalrestat, an Aldose Reductase Inhibitor, on the Generation of Oxygen-Derived Free Radicals in Neutrophils from Streptozotocin-Induced Diabetic Rats

Kashima¹

1998

Endocrinology

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Neutrophil function is impaired by a known mechanism in diabetic patients, thus increasing susceptibility to infections. We studied the effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals and cytosolic sorbitol concentration in neutrophils from streptozotocin-induced diabetic rats. There were four groups: treated and untreated control and diabetic rats. Treated groups were given 0.075% epalrestat in their diet for 4 weeks from the induction of diabetes and were untreated for the subsequent 4 weeks. Oxygen radicals were measured as chemiluminescence amplified by a luciferin analog [Cypridina luciferin analog-dependent chemiluminescence (CLA-DCL), which is dependent on O 2Ϫ generation] and luminol (L)-DCL, which is highly dependent on OCl Ϫ generation) in response to formyl-methonyl-leucyl-phenylalanine. Diabetes resulted in a significant decrease in CLA/L-DCL and a significant increase in sorbitol (P Ͻ 0.01); there was a negative correlation between sorbitol and CLA-DCL (P Ͻ 0.05) in diabetic groups. The 4-week treatment with epalrestat in the diabetic group completely prevented the increase in sorbitol and partially improved the CLA-DCL, although L-DCL was not significantly affected. After 4 weeks off treatment, CLA-DCL decreased and sorbitol increased. Treatment had no effect on serum insulin or glucose concentration. We conclude that an increase in sorbitol in neutrophils causes, in part, an impaired generation of O 2 Ϫ . Epalrestat improves the impaired O 2 Ϫ generation by preventing the sorbitol increase in streptozotocin-induced diabetic rats. (Endocrinology 139: 3404 -3408, 1998)

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Section: Discussionsupporting

confidence: 83%

Section: Materials and Methods Animalsmentioning

confidence: 99%

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Effect of Epalrestat, an Aldose Reductase Inhibitor, on the Generation of Oxygen-Derived Free Radicals in Neutrophils from Streptozotocin-Induced Diabetic Rats

Kashima¹

1998

Endocrinology

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“…In addition, Sato and Shimizu (17) reported that rhG-CSF improves the production of oxygen-derived free radicals in diabetic neutrophils. This suggests that even in the absence of neutropenia, administration of rhG-CSF may be effective for treating infection in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Emphysematous Pyelonephritis Successfully Treated with Nephrectomy and Granulocyte Colony-Stimulating Factor.

Nanki¹,

Ageishi²,

Iwama³

et al. 1994

Intern. Med.

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A 58-year-old womandeveloped diabetic ketoacidosis and emphysematous pyelonephritis caused by Escherichia coli. She was successfully treated with nephrectomy, antibiotics, and recombinant human granulocyte colony-stimulating factor (rhG-CSF). RhG-CSF therapy may be an effective adjunct for diabetic patients with severe infection, even whenneutropenia is not present. (Internal Medicine 33: 234-236, 1994)

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“…Furthermore, diabetes may cause immunological deficiencies, including abnormal neutrophil chemotaxis, phagocytosis, and intracellular killing (5-7). These factors help explain reported clinical failure rates for diabetic foot infections of 20 -30% (3,(5)(6)(7). Thus, several investigators have sought adjunctive therapies for treating these potentially severe infections.…”

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confidence: 99%

Are Granulocyte Colony–Stimulating Factors Beneficial in Treating Diabetic Foot Infections?

et al. 2005

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OBJECTIVE -To assess the value of granulocyte colony-stimulating factor (G-CSF) as adjunctive therapy for diabetic foot infections.RESEARCH DESIGN AND METHODS -We systematically searched the medical literature (including Medline, Embase, LookSmart, and the Cochrane Library) for prospective randomized studies that used G-CSF as an adjunct to standard treatment for diabetic foot infections. Using a conventional meta-analysis, we pooled the relative risks (RRs) for outcomes of interest, including resolution of infection, wound healing, duration of antibiotic therapy, and need for various surgical interventions, using a fixed-effects model. RESULTS -Five randomized trials, with a total of 167 patients, met our inclusion criteria. The methodological quality of the studies was satisfactory. The investigators administered various G-CSF preparations parenterally for between 3 and 21 days. The meta-analysis revealed that adding G-CSF did not significantly affect the resolution of infection or the healing of the wounds but was associated with a significantly reduced likelihood of lower extremity surgical interventions ], number of patients who needed to be treated: 4.5), including amputation (0.41 [0.17-0.95], number of patients who needed to be treated: 8.6). There was no evidence of heterogeneity among the studies or of publication bias, suggesting that these conclusions are reasonably generalizable and robust.CONCLUSIONS -Adjunctive G-CSF treatment does not appear to hasten the clinical resolution of diabetic foot infection or ulceration but is associated with a reduced rate of amputation and other surgical procedures. The small number of patients who needed to be treated to gain these benefits suggests that using G-CSF should be considered, especially in patients with limb-threatening infections. Diabetes Care 28:454 -460, 2005F oot infections in patients with diabetes can be difficult to treat, and therapeutic failure often leads to a lower-extremity amputation (1,2). These infections may be refractory to treatment for several reasons, including inadequate surgical interventions, suboptimal wound care, or severe limb ischemia (3). All infected foot lesions require antibiotic therapy, but their penetration to infected soft tissue and bone may be inadequate, and the incidence of antibiotic resistance is increasing (4). Furthermore, diabetes may cause immunological deficiencies, including abnormal neutrophil chemotaxis, phagocytosis, and intracellular killing (5-7). These factors help explain reported clinical failure rates for diabetic foot infections of 20 -30% (3,5-7). Thus, several investigators have sought adjunctive therapies for treating these potentially severe infections.Granulocyte colony-stimulating factor (G-CSF) is an endogenous hematopoietic growth factor that induces terminal differentiation and release of neutrophils from the bone marrow (8). G-CSF stimulates the growth and improves the function of both normal and defective neutrophils (9), including in patients with diabetes (10). It appears to play a c...

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Granulocyte-Colony Stimulating Factor Improves an Impaired Bactericidal Function in Neutrophils From STZ-Induced Diabetic Rats

Cited by 20 publications

References 0 publications

Effect of Epalrestat, an Aldose Reductase Inhibitor, on the Generation of Oxygen-Derived Free Radicals in Neutrophils from Streptozotocin-Induced Diabetic Rats

Effect of Epalrestat, an Aldose Reductase Inhibitor, on the Generation of Oxygen-Derived Free Radicals in Neutrophils from Streptozotocin-Induced Diabetic Rats

Emphysematous Pyelonephritis Successfully Treated with Nephrectomy and Granulocyte Colony-Stimulating Factor.

Are Granulocyte Colony–Stimulating Factors Beneficial in Treating Diabetic Foot Infections?

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