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ABSTRACT: S-glutathionyl hemoglobin is a proposed biomarker of oxidative stress but has not been measured in sickle cell disease patients. Unlike the S-glutathionyl adduct of normal adult hemoglobin, S-glutathionyl sickle hemoglobin (HbSSG) cannot be directly measured by capillary isoelectric focusing, because it coelutes with fetal hemoglobin (HbF). This suggests that HbF, measured in sickle cell patients with or without hydroxyurea therapy, might contain endogenous HbSSG. As S-glutathionyl hemoglobin can form during sample storage, HbSSG could falsely elevate HbF levels in stored samples. We measured HbSSG based on the quantitative difference in the heterogeneous HbF/HbSSG peak before and after hemolysates were treated with dithiothreitol. Paired t tests showed that dithiothreitol reduced HbF/HbSSG in blood from pediatric sickle cell patients (n=25, mean decrease+/-SD=1.0%+/-0.6, P<0.05) but not in normal infants (n=25). Higher HbF levels in hydroxyurea-treated patients (n=5) were not attributable to HbSSG. HbSSG increased significantly within 1 day in samples stored at -20 degrees C but was unchanged in samples stored 60 days at-70 degrees C. We conclude that blood from sickle cell patients contained up to 2.2% HbSSG, and that endogenous HbSSG is a minor interferent in the measurement of HbF in fresh blood but a major interferent in improperly stored samples.
Journal of Pediatric Hematology/Oncology 10/2009; 31(12):895-900. · 1.16 Impact Factor
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ABSTRACT: We previously REPORTED that mice with diabetes and short-term Helicobacter felis infection had an increase in glycated hemoglobin (HbA1c). Here we report the effect of long-term infection.
Six-week-old C57BL/6 mice were injected with streptozotocin to induce diabetes and started on daily insulin. Following streptozotocin injection, animals were paired according to their HbA1c values and randomized to orally receive either H. felis or culture medium alone. Weight and HbA1c were monitored monthly for 6 months.
Thirty animals corresponding to 15 pairs were included in the study. H. felis-infected diabetic mice developed significantly more gastritis than uninfected animals. Sixteen mice died during the observation period. As compared to uninfected animals, infected mice died more frequently (40% versus 67%, p = .14) and earlier (160 versus 61 days, p = .20); both variables combined showed that H. felis infection significantly decreased the chances of survival during the study period (p = .045). In addition, infected mice showed a trend for higher increase in their HbA1c (0.97 +/- 2.5% versus - 0.22 +/- 3.0%; p = .21) and lower weight gain (2.0 +/- 3.4 g versus 2.9 +/- 2.0 g; p = .15) than uninfected mice.
Long-term H. felis infection had a deleterious effect in mice with streptozotocin-induced diabetes resulting in increased mortality. If the same phenomenon occurs in humans this could lead to interventions to improve the long-term outcome of patients with diabetes.
Helicobacter 01/2006; 10(6):586-91. · 3.15 Impact Factor
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ABSTRACT: Helicobacter pylori infection has been described in association with increases in glycated hemoglobin (HbA(1c)) levels in patients with type 1 diabetes. The purpose of the present study was to use an animal model of Helicobacter infection to test, under controlled conditions, the hypothesis that infection is associated with high HbA(1c) levels. Diabetes was induced in C57BL/6 mice by administration of streptozotocin, and the mice were orally inoculated with H. felis. Six weeks after inoculation, infected mice (n=10) showed gastritis scores significantly greater (P=.01) than those of uninfected mice (n=10). HbA(1c) levels were significantly higher in infected mice with gastritis (11.6%; n=6) than in infected mice without gastritis (8.4%; n=4) or uninfected mice (7.6%; n=10). It was concluded that gastritis induced by H. felis is associated with increased HbA(1c) levels in the mouse model of streptozotocin-induced diabetes.
The Journal of Infectious Diseases 06/2002; 185(10):1463-7. · 6.41 Impact Factor