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This study investigated differences among patients with impaired fasting glucose (IFG) and hemoglobin A1c (HbA1c)-defined prediabetes (A1c-PDM); we compared insulin resistance and the prevalence of microalbuminuria (MAU) in these individuals.A total of 982 patients with newly diagnosed PDM and 455 non-PDM healthy individuals were evaluated. Serum insulin, HbA1c, fasting plasma glucose (FPG), and urine albumin excretion (UAE) levels were measured. The homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) was calculated.MAU was more prevalent in patients with IFG than in those with A1c-PDM (13.2% versus 6.4%,Patients with IFG may be at a greater risk of insulin resistance and possible progression to diabetic nephropathy than patients with A1c-PDM.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on eosinophil activation, atopic sensitization, and systemic inflammation in allergic diseases has rarely been investigated. This study aimed to investigate the relationship between NGAL, eosinophil cationic protein (ECP), cytokines, and allergen-specific immunoglobulin E (sIgE) in allergic diseases. A total of 136 patients with allergies and 58 healthy individuals were evaluated. The concentrations of NGAL, ECP, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), sIgE, total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) were measured. The transforming growth factor-β1 (TGF-β1) level was measured as a profibrotic marker of bronchial asthma. Allergic patients had significantly higher NGAL, ECP, and hsCRP levels than healthy individuals. However, there was no significant difference in NGAL levels between patients with positive and negative ECP tests and those with high and low sIgE scores. Asthmatic patients with elevated NGAL exhibited a significantly higher TGF-β1 level than those without elevated NGAL. However, no significant difference was observed in the ECP, IL-5, and sIgE levels between the two groups. Among the patients with a positive ECP test, subjects with elevated hsCRP had two times higher NGAL levels than those without elevated hsCRP. NGAL was positively correlated with TNF-α, TGF-β1, and hsCRP, but not with ECP, IL-5, tIgE, and sIgE. An elevated NGAL level led to a 1.3-fold increase in the prevalence of high TGF-β1 (odds ratio: 1.31; 95% CI: 1.04–2.58; P < 0.001 ). In conclusion, NGAL elevation may be more closely linked to allergic inflammation and a possible fibrotic change in the airways than to the severity of eosinophil activation and atopic sensitization.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on fetal hemoglobin (HbF) levels in diabetic patients is rarely investigated. This study is aimed at investigating the possible association between NGAL and HbF levels in type 2 diabetes mellitus (T2DM). A total of 160 patients with T2DM and 61 healthy individuals were evaluated. NGAL, HbF, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and urine albumin levels were measured. HbF levels were significantly higher in patients with elevated NGAL than in those without elevated NGAL (1.44% versus 0.94%, P = 0.001 ). High HbF was 2.3 times more prevalent in patients with elevated NGAL than in those without elevated NGAL. In addition, NGAL, TNF-α, and IL-5 levels were significantly higher in patients with high HbF than in those with low HbF; however, there was no significant difference in HbA1c and FPG levels between the two groups. HbF was positively correlated with NGAL ( r = 0.275 , P < 0.001 ), TNF-α ( r = 0.256 , P < 0.001 ), and IL-5 ( r = 0.212 , P < 0.001 ), but not with HbA1c and FPG. An elevated NGAL level led to a 1.27-fold increase in the prevalence of high HbF (odds ratio: 1.27, 95% CI: 1.03–2.51, and P < 0.001 ). The diagnostic efficacy of NGAL to identify an elevated HbF level was superior to that of HbA1c (area under the curve: 0.697, 95% CI: 0.609–0.786 versus 0.584, 95% CI: 0.488–0.681, and P = 0.022 ). In conclusion, enhanced NGAL production may be closely linked to elevated HbF in conjunction with proinflammatory cytokines in patients with T2DM.

Hereditary spherocytosis (HS) is a congenital disorder of the red blood cell membrane and is characterized by hemolytic anemia, variable jaundice, and splenomegaly. In neonates, the diagnosis of HS can be difficult in the absence of family history. Herein, we describe clinical and molecular genetic findings in a Korean neonate with HS. A one-month-old girl presented with severe anemia and jaundice. Spherocytes were frequently observed on peripheral blood smear, but the erythrocyte osmotic fragility test result was normal. Targeted next-generation sequencing (NGS) revealed the patient was heterozygous for a novel frameshift mutation, c.191_194del (p.Leu64Argfs*7), in exon 3 of

IntroductionThe association between serum soluble apoptotic markers, eosinophil cationic protein (ECP), and inflammatory parameters in allergic diseases has seldom been studied. This study aimed to investigate apoptotic activity in allergic diseases and its relationship with ECP, systemic inflammation, and severity of atopic sensitisation.Material and methodsA total of 125 patients with allergic diseases were investigated by measuring ECP, APO-1, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), allergen-specific immunoglobulin E (sIgE), total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) levels.ResultsECP, APO-1, TRAIL, and hsCRP levels were significantly higher in patients with allergic diseases than in healthy individuals. Patients who tested positive for ECP had no significant differences in APO-1 and TRAIL levels compared with those who tested negative for ECP. However, among the patients who tested positive for ECP, those with elevated hsCRP concentrations had significantly higher APO-1 and TRAIL levels than those without elevated hsCRP concentrations (p < 0.001, respectively). APO-1, TRAIL, and ECP levels were significantly higher in patients with inhalant allergy than in those with food allergy. APO-1 and TRAIL were significantly associated with hsCRP but not with tIgE and sIgE scores.ConclusionsApoptotic activity is enhanced in allergic diseases and is more closely linked to concomitant systemic inflammation than to the severity of atopic sensitisation, particularly in patients with inhalant allergy.

This study investigated the association of a tobacco-specific nitrosamine carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) with urinary cotinine (uCot), urinary sodium (uNa) excretion, systolic blood pressure (sBP), and total energy intake in adolescents and children in relation to the subjects' age. A total of 790 subjects aged 6-19 years were evaluated. NNAL, uCot, corrected NNAL (cNNAL), the NNAL/uCot ratio, uNa, sBP, and nutrient intake were measured. A strong association between uCot and cNNAL was observed in children who were 11 years of age (r=0.881, P

This study aimed to investigate a delta index of the estimated glomerular filtration rate (δeGFR-index) to amend an overestimated neutrophil gelatinase-associated lipocalin (NGAL) level in systemic inflammatory response syndrome (SIRS). A δeGFR-index was computed, and the NGAL/δeGFR-index was determined. Patients with SIRS exhibited significantly higher levels in NGAL, the δeGFR-index, and high sensitivity C-reactive protein (hsCRP) than non-SIRS inflammatory patients (216 ng/ml, 1.32, and 5.64 mg/dl vs. 153 ng/ml, 1.18, and 2.92 mg/dl, respectively, p p p 3.80 mg/dl in SIRS [0.761 (95% CI, 0.660–0.862) vs. 0.728 (95% CI, 0.625–0.831), p = 0.019]. In short, the NGAL/δeGFR-index more correctly represents the disease activity in SIRS than the level of plasma NGAL. A measure of the NGAL/δeGFR-index may be of additional help when monitoring patients with SIRS, particularly in conjunction with concurrent renal dysfunction.

The significance of low plasma neutrophil gelatinase-associated lipocalin (NGAL) level in systemic inflammation has not been investigated. The aim of this study was to investigate low plasma NGAL level in systemic inflammation and its relationship with proinflammatory cytokines, procalcitonin (PCT), leukocyte profiles, nutritional status, and kidney function.Patients with systemic inflammation were evaluated by measuring NGAL, PCT, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), serum creatinine (sCr), and clinical scores.Of 191 patients, 30 (15.7%) had low NGAL levels (68 ng/mL), and 102 (53.4%) had elevated NGAL levels (150 ng/mL). Among the 30 patients with low NGAL levels, 26 (86.7%) had normal kidney function and 24 (80.0%) had low-grade inflammation. In comparison with healthy individuals, patients with low NGAL levels had higher levels of TNF-α, IL-6, PCT, and hsCRP but not absolute neutrophil count (ANC). Neutropenia was more often observed in subjects with low NGAL levels than in those with elevated NGAL levels (16.7% versus 1.9%, p0.001). In the low NGAL group, plasma NGAL was significantly associated with ANC (r = 0.312, p0.001) but not cytokines, sCr, nutritional parameters, and clinical scores. Receiver operating characteristic (ROC) curve analysis demonstrated that the diagnostic ability of the ANC for identifying low NGAL levels was superior to that of PCT and TNF-α [0.82 (95% CI, 0.75 - 0.89) versus 0.67 (95% CI, 0.56 - 0.79) and 0.66 (95% CI, 0.54 - 0.78), respectively, p0.001].Low plasma NGAL level in systemic inflammation was more closely linked to the non-increment of the ANC than proinflammatory cytokines, PCT, and nutritional status, particularly in patients with low-grade inflammation who had preserved kidney function.

The aim of this study was to investigate the relationships between apoptotic markers and the levels of glycated and fetal hemoglobin (HbA1c and HbF) in diabetes.The levels of Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), HbF, and HbA1c were measured in 112 patients with type 2 diabetes.Diabetic patients with microalbuminuria had an elevated Fas level and a decreased TRAIL level, compared to healthy controls. Elevated HbF level was more often observed in patients with decreased TRAIL level than in those with increased TRAIL level (33.9% versus 12.5%, p0.05). Fas was positively correlated with HbA1c (r = 0.31, p0.001), but TRAIL was inversely correlated with HbA1c and HbF (r = -0.30 and r = -0.32, respectively; p0.001). In a multivariate logistic regression analysis, decreased TRAIL level was significantly associated with enhanced HbF production after adjusting for potential confounders [odds ratio, 1.35 (95% CI, 1.09 - 2.87), p = 0.004]. The diagnostic ability of TRAIL to identify an elevated HbF1.0% was significantly higher than that of the Fas [0.760 (95% CI, 0.638 - 0.882) versus 0.589 (95% CI, 0.457 - 0.721), p0.001].Fas is closely associated with long-term hyperglycemia, while TRAIL plays certain roles in enhancing HbF production in type 2 diabetes.

The aim of this study was to assess the significance of the neutrophil gelatinase-associated lipocalin/serum creatinine ratio (NGAL/sCr ratio) in patients with renal dysfunction. The percent difference between plasma NGAL level and the NGAL/sCr ratio was 36.7% (95% CI, 18.4–83.7%) in patients with sCr level ≥ 1.2 mg/dL. In a multivariate analysis, high sensitivity C-reactive protein (hsCRP) was significantly associated with the NGAL/sCr ratio and plasma NGAL level (r=0.526andr=0.453, resp.,P<0.001). In a receiver operating characteristics curve, the diagnostic ability of the NGAL/sCr ratio to identify hsCRP > 4.0 mg/dL was superior to that of NGAL [0.783 (95% CI, 0.674–0.892) versus 0.733 (95% CI, 0.615–0.852),P=0.032]. The area under the curve of the NGAL/sCr ratio was larger than that of hsCRP to detect corrected erythrocyte sedimentation rate > 25 mm/h and the neutrophil-to-lymphocyte ratio >4.5 in renal dysfunction. In short, the NGAL/sCr ratio may offer useful information when screening patients with both systemic inflammation and renal dysfunction.

Studies on neutrophil gelatinase-associated lipocalin (NGAL) as an iron-regulatory protein are limited. This study investigated the relationships between plasma NGAL levels and indices of anemia in 187 patients with systemic inflammation. Plasma NGAL levels were significantly higher in patients with anemia versus in patients without anemia (185 ng/mL versus 98 ng/mL;P< 0.001). Serum iron levels were lower in patients with NGAL > 156 ng/mL than in those with NGAL ≤ 156 ng/mL (27.4 ± 25.3 µg/dL versus 58.1 ± 43.5 µg/dL;P< 0.001). In a receiver operating characteristic curve, the diagnostic ability of NGAL to identify anemia was superior to that of high-sensitivity C-reactive protein [0.712 (95% CI, 0.618–0.787) versus 0.649 (95% CI, 0.573–0.744);P< 0.01]. In a multivariate logistic regression analysis, the elevated NGAL level was significantly associated with the presence of anemia after adjusting for potential confounders [odds ratio, 1.30 (95% CI, 1.07–2.58);P= 0.010]. In conclusion, enhanced NGAL production may contribute to the development of anemia in patients with systemic inflammation.

This study investigated the use of corrected neutrophil gelatinase-associated lipocalin (cNGAL) values to screen renal dysfunction in patients with systemic inflammation. Plasma NGAL concentrations were measured using a fluorescent immunoassay in 259 patients with inflammatory diseases. An inflammation index was calculated using a scoring system based on high-sensitivity C-reactive protein (hsCRP) and corrected erythrocyte sedimentation rates. The uncorrected NGAL (uNGAL) concentration increased with the inflammation index, but cNGAL increased in parallel with serum creatinine (sCr) levels. After adjustment with the inflammation index, increased uNGAL concentrations returned to a level not significantly different from the control value. In a multivariate regression analysis, hsCRP was more closely associated with uNGAL than cNGAL [r=0.513 (p0.001) vs. r=0.201 (p=0.017)], but the sCr level was more strongly linked to cNGAL than uNGAL (r=0.692 vs. r=0.583, respectively, p0.001). In a receiver operating characteristics (ROC) curve analysis, the diagnostic accuracy of cNGAL, which identifies an increase of sCr ≥0.3 mg/dL within 48 hours, was found to be superior to that of uNGAL [0.72 (95% CI, 0.61-0.84) vs. 0.67 (95% CI, 0.56-0.81), p=0.038]. In conclusion, cNGAL more accurately reflects renal dysfunction than uNGAL under inflammatory conditions. A measurement of cNGAL may provide helpful information for assessing patients with renal impairment, particularly in association with systemic inflammation.

This study investigated the relationship between the urine homocysteine/creatinine (uHcy/Cr) ratio and the levels of natural anticoagulants, proinflammatory cytokines, and nitric oxide (NOx) metabolites in cerebrovascular diseases. No significant differences were observed in protein C, protein S, and antithrombin III levels among subjects with serum Hcy (sHcy)15.0 μmol/L and ≤15.0 μmol/L. However, subjects with a uHcy/Cr ratio14.8 μmol/g Cr showed significant differences in the levels of the corresponding parameters than those with uHcy/Cr ratio ≤14.8 μmol/g Cr. The sensitivity and specificity of the sHcy level at a cutoff of 15.0 μmol/L were 32.6% and 85.7%, respectively, with a positive predictive value of 69.5%. In contrast, those values for the uHcy/Cr ratio at a cutoff of 14.8 μmol/g Cr were 55.1% and 91.4% with a positive predictive value of 86.5%. The uHcy/Cr ratio correlated more closely with protein C, antithrombin III, TNF-α, and NOx levels than did sHcy concentrations. In short, the uHcy/Cr ratio has a significant relationship with anticoagulation- and inflammation-related parameters. A measurement of the uHcy/Cr ratio may provide helpful information for assessing patients with cerebrovascular diseases.

To investigate the relationship between hematopoiesis and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we measured soluble TRAIL concentrations, reticulocytes, hemograms, and anthropometric variables in 156 healthy subjects. Serum TRAIL concentrations were analyzed by an enzyme immunoassay. Serum ferritin, thyroid hormone, total cholesterol, creatinine, and blood glucose levels were determined. There were no significant differences in blood cell counts and biochemical parameters between the subjects with TRAIL less than 63.5 pg/ml and TRAIL at least 63.5 pg/ml, nor between those with TRAIL at most 47.5 pg/ml (20th percentile) and TRAILor =80.9 pg/ml (80th percentile). However, hemoglobin, mean corpuscular hemoglobin (MCH), and MCH concentration (MCHC) averaged 15.6+/-0.8 g/dl, 31.9+/-1.1 pg, and 34.5+/-0.9 g/dl in the subjects with TRAIL at most 47.5 pg/ml, which were significantly above the values in those with TRAIL at least 80.9 pg/ml (14.7+/-0.9 g/dl, 30.4+/-1.3 pg, and 33.2+/-1.2 g/dl, P0.05, respectively). Serum TRAIL levels were significantly higher in the subjects with decreased MCH than in those with elevated MCH. Soluble TRAIL concentrations were significantly correlated with hemoglobin (r=-0.25, P0.05), MCH (r=-0.32, P0.05), and MCHC (r=-0.29, P0.05), but not correlated with leukocyte differentials and platelet counts. In conclusion, soluble TRAIL does not seem to influence leukocyte and platelet production but has an important relationship to erythropoiesis in healthy adults.

To investigate whether nitric oxide (NO) production is associated with serum lipid concentrations and body mass index (BMI), we measured serum nitrate and nitrites (NOx) concentrations, serum lipid profiles, and anthropometric parameters in 319 adolescents.Serum NOx concentrations were determined using the Griess reaction. Serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by standard enzymatic procedures.Subjects with increased serum cholesterol or triglyceride concentrations exhibited remarkably high NOx levels. Total cholesterol and triglyceride averaged 161.5+/-27.4 and 205.9+/-107.8 mg/dl in males with NOx92.8 micromol/l (upper 20%), which were significantly above the values (132.4+/-17.2 and 58.1+/-20.3 mg/dl) in those with NOx15.6 micromol/l (lower 20%). The prevalences of male adolescents with increased concentrations of cholesterol and triglyceride were significantly higher in the subjects with NOxor =51.2 micromol/l than in those with NOx51.2 micromol/l (8.9% and 22.2% vs. 1.6% and 2.3%, p0.05, respectively). Correlation coefficients of serum lipid concentrations and anthropometric parameters vs. serum NOx concentrations were higher in males than in females for cholesterol (r=0.28 vs. 0.23), triglyceride (r=0.51 vs. 0.42), HDL-C (r=-0.25 vs. -0.16), and BMI (r=0.39 vs. 0.27).NO production is closely associated with serum lipid concentrations in adolescents, and these associations are stronger in males than in females.

To investigate the relationships between respiratory function and osteoporosis, 132 premenopausal and 98 postmenopausal women were evaluated.Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Pulmonary function and anthropometric parameters were measured using a spirometer and a body composition analyzer.Lumbar spine and proximal femur BMDs in postmenopausal women with forced expiratory volume in 1s (FEV1)or = 92.0% averaged 0.83 +/- 0.12 g/cm2 and 0.67 +/- 0.11 g/cm2, which were significantly above the values (0.76 +/- 0.14 g/cm2 and 0.61 +/- 0.12 g/cm2, P0.05) in those with FEV192.0%. The prevalences of osteoporosis at lumbar spine and proximal femur were 59.2 and 46.9% in the postmenopausal women with peak expiratory flow rate (PEFR)5.12 l/s, significantly higher than those of osteoporosis at the corresponding sites in the women withor = 5.12 l/s (36.7 and 20.4%, P0.05). Lumbar spine and proximal femur BMDs were positively correlated with FEV1 (r = 0.28, P0.05; r = 0.31, P0.05) and PEFR (r = 0.35, P0.05; r = 0.23, P0.05) in postmenopausal women; however, no significant correlations were observed in premenopausal women.Pulmonary function seems to be more closely associated with BMD in postmenopausal women than in premenopausal women. Poor respiratory function may be an indicator of postmenopausal women at increased risk of osteoporosis.

Background: This study investigated the relationships of bone mineral density (BMD) with body composition, basal metabolic rate (BMR), and fat distribution. Methods: We measured body mass index (BMI), anthropometrics, and BMD in 345 postmenopausal women and 224 elderly men. Total body fat (TBF), fat distribution, and BMR were assessed using a body composition analyzer. Lumbar spine and proximal femur BMDs were measured with dual-energy X-ray absorptiometry. Results: Lumbar spine BMD was more strongly correlated with BMR (r=0.51, p

To investigate the associations of body mass index (BMI) and total body fat (TBF) vs. blood lipid concentrations, we measured six anthropometric parameters, body fat mass, and serum lipid profiles in 1529 apparently healthy adults.TBF was assessed using a body fat analyzer. Serum concentrations of triglyceride, total cholesterol, and low- or high-density lipoprotein cholesterol (LDL-C or HDL-C) were determined by standard enzymatic procedures.Serum lipid concentrations were more strongly correlated with TBF than with BMI or waist circumference in both men and women. The mean concentrations of total cholesterol in the subjects with high fatness (TBF95th percentile) were significantly higher than those for the subjects with low fatness (TBF5th percentile; p0.01), but no significant differences were observed in serum lipid levels between overweights (BMI95th percentile) and underweights (BMI5th percentile). The incidence of hypercholesterolemia was significantly higher in the subjects with high fatness (TBF95th percentile) than the corresponding overweight subjects (BMI95th percentile; p0.01).TBF is more strongly associated with serum lipid concentrations in adults, at least as compared to BMI.

To investigate the relationship between coagulation activities and the fibrinolytic system during normal pregnancy, we measured the plasma concentrations of coagulation factors, antithrombin III (AT III), D-dimer, tissue plasminogen activator (tPA), total protein S (TPS), and plasminogen activator inhibitor type 1 (PAI-1) in 436 apparently healthy pregnant, postpartum, and nonpregnant women. There were no significant changes in AT III, TPS, and factor XI concentrations during pregnancy and puerperium. However, factor VII, VIII, IX, and XII activities increased gradually as pregnancy progressed, reached maximum values in the third trimester, and returned to nonpregnant levels by 5-8 weeks postpartum. Plasma D-dimer levels in the third trimester of pregnancy were 1.23+/-0.42 micro g/ml, significantly higher than for the first trimester (0.34+/-0.16 micro g/ml, P

Objective. This study investigated the use of the estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to screen forβ-cell function in pediatric diabetes.Methods. Glycated hemoglobin (HbA1c), glycated albumin (GA), fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c (GA/A1c ratio) was calculated, and the homeostasis model assessment ofβ-cell function (HOMA-β) was determined.Results. Median values of C-peptide, insulin, and HOMA-βlevels were significantly higher in patients with an increased eAG/fPG ratio than in those with a decreased eAG/fPG ratio. C-peptide and HOMA-βlevels were more closely correlated with the eAG/fPG ratio than with GA, HbA1c, the GA/A1c ratio, and fructosamine. In contrast, body mass index was significantly associated with GA, GA/A1c ratio, and fructosamine, but not with the eAG/fPG ratio and HbA1c levels. To test the diagnostic accuracies of the eAG/fPG ratio for identifying HOMA-β> 30.0% in patients with type 2 diabetes, the area under the ROC curve of the eAG/fPG ratio was significantly larger than that of the GA/A1c ratio [0.877 (95% CI, 0.780–0.942) versus 0.775 (95% CI, 0.664–0.865),P=0.039].Conclusions. A measurement of the eAG/fPG ratio may provide helpful information for assessingβ-cell function in pediatric patients with diabetes.

To investigate the influence of iron deficiency and iron supplementation on nitric oxide (NO) production, we measured serum iron markers, serum nitrate and nitrite (NOx) concentrations, reticulocyte maturity index (RMI), and serum transferrin receptor (sTfR) levels in 369 females aged 14-19 years. RMI was analyzed by flow cytometry, sTfR concentrations were measured by enzyme immunoassay, and serum NOx levels were tested by the Griess reaction. NOx concentrations of the subjects in iron depletion phase were significantly higher than those of healthy controls. NOx concentrations increased gradually as iron deficiency progressed and were threefold higher than for the healthy controls, when the subjects attained a frank iron deficiency anemia. In particular, the NOx concentrations were 7.5-fold higher in the patients with severe iron deficiency anemia (Hb80 g/l) than for the subjects with high hemoglobin value (Hbor=140 g/l). The increased NOx concentrations (132.6+/-42.1 microM) observed in the group with severe anemia decreased significantly (46.3+/-15.8 microM) after hemoglobin levels were normalized by iron supplementation ( P0.01). NOx concentrations correlated inversely with hemoglobin levels ( r(2)=0.202, P0.01), but correlated positively with the sTfR concentrations ( r(2)=0.322, P0.01) and the RMI ( r(2)=0.369, P0.01). In conclusion, iron deficiency anemia increases NO production, and elevated NOx concentrations in iron deficiency anemia return to normal with iron supplementation.

Objectives. This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. Methods. Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. Results: (1) Mean sTfR concentration was 2.63±1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. Conclusion. The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.

NO is produced in many different cells and is involved in the regulation of such physiological and pathophysiological processes as inflammation, vasodilation, and metabolism (1). Depending on the cell type, NO is produced in an enzymatic reaction catalyzed by one of the three isoforms of NO synthase (NOS): neuronal NOS, endothelial NOS, and inducible NOS (2). Measurement of the NO metabolites, nitrate and nitrite (NOx), is also important as a marker of NOS enzyme activity. Obesity is a condition involving an excess accumulation of body fat, and the prevalence of obesity is rapidly increasing worldwide. Excessive weight and obesity are leading to nutrition-related disorders of clinical and public health concern. Recent studies have suggested a role for NO in the regulation of food intake in an animal experiment (3)(4). Endothelial and inducible NOS have been shown to be present in adipose tissue of the rat (5), suggesting that adipose tissue may be a potential source of NO production. Previous reports demonstrated that NOS activity and inducible NOS protein were also present in human subcutaneous adipose tissue (6) and showed that inhibition of NOS led to increased lipolysis in this tissue (7). However, how NO production changes as body mass index (BMI) increases in apparently healthy subjects has not been studied extensively. Moreover, correlation studies of serum NOx concentrations, body fat mass, and blood lipid concentrations in healthy subjects are limited. Therefore, in the present study, we investigated the changes in NOx concentrations according to BMI and evaluated the relationships among NOx concentrations, total body fat, and lipid profiles in adolescents. We measured serum NOx concentrations, complete blood cell counts, iron markers, and serum lipid profiles in 185 males and 178 females, 14–19 years of age, selected from 1473 students attending middle or high school. Eight anthropometric measurements were …

To investigate the influence of body iron status on reticulocyte subpopulations and reticulocyte maturity index (RMI), we measured serum iron markers, fluorescent intensity of reticulocytes, and serum transferrin receptor (sTfR) concentrations in 374 females aged 14-19 years. Reticulocyte subpopulations were analyzed by flow cytometry, and sTfR concentration was measured by enzyme immunoassay. There were no significant differences in the values of reticulocyte subpopulations and RMI between ferritin alone-depleted group and healthy controls. However, middle- and high-fluorescence reticulocytes and RMI were significantly higher in both the serum iron- and serum ferritin-depleted groups than in the ferritin alone-depleted group. Middle-fluorescence reticulocytes and RMI increased gradually as the body iron store was depleted and were 3.4- and 3.6-fold higher, respectively, than normal controls, when the subjects attained a frank iron-deficiency anemia. There were no significant changes in the values of red blood cells or total reticulocyte counts during iron-depleted states. The mean value of sTfR (3.98 mg/l) in the subjects with RMI > or = 1.5% was significantly higher than that (2.26 mg/l) in the subjects with RMI < 1.5% (P < 0.01). The sTfR concentration correlated significantly with RMI (r = 0.61, P < 0.01) and middle-fluorescence reticulocytes (r = 0.59, P < 0.01). In short, body iron depletion induces elevation of immature reticulocyte fractions and RMI.

Aim: To investigate the association between Helicobacter pylori (H. pylori) infection and iron deficiency anaemia (IDA). Methods: Haemoglobin levels, iron parameters and serum IgG antibodies to H. pylori were measured in 693 children aged 9 to 12 y. Results: No significant differences in the seroprevalence of H. pylori infection and antibody titres to H. pylori were found between the IDA group and the non-anaemic controls. Conclusion: H. pylori infection does not seem to contribute to iron deficiency in prepubescent children.

Patients were eligible if they had the following: (1) a documented clinical history of acute asthma, (2) positive results for sIgE test (aeroand/or food allergens according to the ImmunoCAP test), and (3) elevated serum total IgE (tIgE) levels to confirm allergy. The exclusion criteria were as follows: (1) medication history including corticosteroids or histamine antagonists, (2) concurrent systemic infection with fever (>37.5 ° C), or (3) chronic illness. The following parameters were measured: eosinophil parameters (ECP and ECP/Eo ratio), IgE-related parameters (sIgE score and tIgE level), cytokines (IL-5 and TNF-α), and inflammatory parameters [NOx metabolites and high-sensitivity C-reactive protein (hsCRP)]. The serum ECP concentration was measured using a solid-phase, 2-site chemiluminescent immunometric assay on an Immulite 2000 analyzer (Siemens Healthcare Diagnostics, Tarrytown, N.Y., USA). The cutoff limit for a positive serum ECP result was set at >19 μg/l on the basis of the manufacturer’s instruction. sIgE was measured for 2 major inhalant allergens (Dermatophagoides pteronyssinus and D. farinae) and 2 food allergens (egg white and cow’s milk) using a fluoroenzyme immunoassay system (ImmunoCAP 100, Phadia AB, Uppsala, Sweden). sIgE concentrations >0.35 kU/l Eosinophils contain several proinflammatory mediators and are implicated in the initiation of diverse inflammatory responses [1] . Eosinophil cationic protein (ECP) is produced in eosinophilic progenitors, stored in cytoplasmic granules of mature eosinophils, and released from activated eosinophils [2, 3] . The ratio of serum ECP concentrations to peripheral blood eosinophil counts (ECP/Eo ratio) reflects the number of ECP molecules per circulating eosinophil, which is regarded as a potential indicator of eosinophil activation [4, 5] . Few studies have closely examined the relationships between the activation of eosinophils and the production of nitric oxide (NOx) and cytokines. The present study investigated the associations between eosinophil activation and the levels of interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α), NOx metabolites, and allergen-specific immunoglobulin E (sIgE) scores. A total of 112 patients with acute bronchial asthma (57 males and 55 females) aged 3.2–9.5 years (median 6) were investigated. Ageand gender-matched healthy subjects (n = 25) were evaluated as a control group, who had no evidence of allergic diseases and atopic sensitization based on skin-prick test results. Received: January 9, 2013 Accepted after revision: February 17, 2013 Published online: July 11, 2013

Flow cytometric analysis enables evaluating maturation of reticulocytes by quantitating the fraction of reticulocytes within low-, middle-, and high-fluorescence intensity regions (LFR, MFR, and HFR, respectively) [1]. The immature reticulocyte fraction (IRF), the sum of MFR and HFR, which corresponds to young reticulocytes released prematurely, is a useful parameter to evaluate the erythropoietic activity in anemia. The reticulocyte maturity index (RMI) is calculated from the proportion of reticulocyte subpopulations and can be used as the earliest and most sensitive predictor of erythropoiesis [2]. The premature destruction of erythroid precursors in the medullary cavity is termed ineffective erythropoiesis and occurs normally in less than 10% of the developing cells [3]. However, loss of much larger numbers of cells is seen in myelodysplastic syndromes (MDS), megaloblastic anemia, hemoglobinopathies, and several rare congenital anemias such as congenital dyserythropoietic anemias. MDS are bone marrow stem cell disorders characterized by ineffective hematopoiesis leading to blood cytopenias despite the presence of a cellular marrow and a propensity towards leukemic transformation [4]. There have been few studies, which have closely examined the production of reticulocytes in the bone marrow from patients with MDS and the significance of the ratio of reticulocyte subpopulations. Hence, in this study we assessed the immature reticulocytes and RMI using flow cytometry in both bone marrow and peripheral blood from MDS patients and compared the values to those of non-MDS patients as well as healthy controls. The number of mature reticulocytes and immature reticulocyte subpopulations were measured with flow cytometry in bone marrow and venous blood samples from 72 MDS patients and 65 controls (70 males, 67 females, age range: 51–76 years). The MDS patients included 31 with refractory anemia (RA), 12 RA with ringed sideroblasts, and 29 RA with excess of blasts. We studied 34 ageand gender-matched nonanemic individuals as controls, who had no hematologic disorders. As additional controls, we also assessed the reticulocytes in the bone marrow from non-MDS patients (n=31) with anemia but with no evidence of ineffective erythropoiesis such as carcinoma (n=12) and lymphoma (n=19) not involving the bone marrow. Because reticulocyte production is affected by the degree of anemia, we compared MDS patients not only to the healthy controls but also to non-MDS patients who showed similar hemoglobin levels to MDS patients. Bone marrow and peripheral blood specimens were obtained at initial presentation from patients, and none of the patients had received any specific therapy prior to the study. Complete blood cell count was determined using an electronic counter (SE 9000, Sysmex, Kobe, Japan). Reticulocytes and their subpopulations were automatically analyzed by flow cytometry (R-3000, Sysmex, Kobe, Japan). The corrected reticulocyte count was calculated, based on a normal hematocrit of 45%, using the following formula: corrected reticulocyte (%) = (subject’s hematocrit/45) reticulocyte count (%). RMI was calculated using the equation: RMI = (MFR + HFR) 100/LFR and expressed as the percentage [5]. We compared the values of reticulocytes, corrected reticulocytes, IRF, and RMI of bone marrow (BM) to those of peripheral blood (PB). The Mann-Whitney U test was used to compare differences of mean values. P

This study investigated the potential contribution of nitric oxide (NOx) production to enhanced fetal hemoglobin (HbF) synthesis in patients with diabetes. Glycated hemoglobin (HbA1c), HbF, high sensitivity C-reactive protein (hsCRP), plasma glucose levels, and serum NOx concentrations were measured in 350 diabetics and 125 healthy subjects. There were no significant correlations between HbF and HbA1c levels, nor between HbF and plasma glucose levels. However, serum NOx concentrations in patients with HbF1.0% (76.2 ± 32.4 μmol/L) were significantly higher than those with HbF ≤ 1.0% (47.3 ± 29.8 μmol/L, p0.05). Inversely, patients with moderately increased serum NOx levels98.1 μmol/L (75th percentile of patients) exhibited significantly higher HbF levels than those with decreased serum NOx levels34.2 μmol/L (25th percentile of patients) (1.16 ± 0.41 vs. 0.62 ± 0.28%, p0.05). After excluding the subjects with high NOx levels, elevated HbF concentrations returned to a level not significantly different from the control value. Serum NOx concentrations were significantly correlated with HbF (r = 0.32, p0.05) and hsCRP levels (r = 0.35, p0.05) in diabetic patients. In conclusion, long-term glycemic control does not contribute to fetal-type erythropoiesis, but increased NOx production seems to play an important role in the enhanced HbF synthesis of diabetics.

Among the physiologic changes during pregnancy, the disproportionate increases in plasma volume and red cell mass produce a decrease in hemoglobin concentration. Pathologic anemia of pregnancy is mostly attributable to iron deficiency associated with increased requirements and inadequate intake (1), but physiologic changes also occur in iron markers. Iron plays an essential role in a spectrum of metabolic processes. Cellular iron uptake is facilitated by transferrin receptor (TfR)-mediated endocytosis (2). Serum TfR (sTfR) is a sensitive indicator of iron deficiency in inflammatory states and in the anemia of chronic diseases because its concentration is not influenced by the acute phase response (3). The sTfR concentration is closely related to erythroid TfR turnover; therefore, sTfR may be a useful marker to monitor erythropoiesis in various clinical situations (4). Erythropoiesis is a highly dynamic process and can be monitored by quantitative reticulocyte counting. Flow cytometric analysis of reticulocytes provides a quantitative reticulocyte measurement with high sensitivity and precision (5). The fluorescence intensity of reticulocytes is directly proportional to erythrocyte RNA content, and reticulocytes can be divided into three subpopulations by fluorescence intensity: low fluorescence reticulocytes, middle fluorescence reticulocytes, and high fluorescence reticulocytes (5)(6). The reticulocyte maturity index (RMI) is calculated from the proportion of reticulocyte subpopulations and can be used as the earliest and most sensitive predictor of bone marrow erythropoiesis (6). The sTfR concentration and the RMI during normal pregnancy have not been studied extensively, and the reported values for sTfR show a wide range of discrepancies. Therefore, in the present study, we investigated the sequential changes in sTfR concentrations according to gestational age in healthy pregnant women without anemia and iron deficiency. We …

This study investigated the relationship between calculated immature granulocyte (IG) counts and the severity of sepsis. Coagulation parameters, fibrinolytic indices, bacterial isolation rates in blood cultures, and mortality were observed in 237 patients with suspected sepsis. The difference in leukocyte subfractions (delta neutrophil index; DN) identified by a cytochemical myeloperoxidase reaction and by a nuclear lobularity assay was determined with a blood cell analyzer (ADVIA 120, Siemens, Inc.). DN was strongly correlated with manual IG counts (r = 0.75, p0.05). Patients with high DN (40%) averaged 40% lower in platelet count, 26% prolongation of prothrombin time (PT), and 35% diminution of antithrombin III (AT III) activity, vs those with low DN (5-20%). Overt disseminated intravascular coagulation was more prevalent as the DN increased, and reached a peak in patients with DN40%. DN values were closely associated with PT (r = 0.35, p0.05), AT III activity (r = -0.36, p0.05), and platelet count (r = -0.27, p0.05). Positive blood culture rate averaged 3.5-fold higher in patients with DN40% vs the subgroup with low DN of 5-10%. The mortality rate of patients with DN40% markedly exceeded the mortality rate of patients with DN of 5-10% (79% vs 15%, p0.05). Thus, DN has implications for the severity of sepsis and may be valuable to assess the prognosis of patients with suspected sepsis.