Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia.

BACKGROUND: We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy-induced bacterial infections in children with B acute lymphoblastic leukemia (B-ALL). PROCEDURE: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were determined in children with B-ALL. FCN2 haplotype was determined by gene sequencing. Number and duration of FN episodes as well as number of bacterial infections were recorded during induction chemotherapy. RESULTS: Forty-four children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in 44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not associated with increased frequency of FN episodes. MBL2 medium/high-risk genotype and FCN2 medium/high-risk haplotype were associated with prolonged duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of bacterial infections (P = 0.001 and P = 0.002, respectively). The combined MBL2/FCN2 medium/high-risk genotype was associated with an increased number of bacterial infections (P = 0.001). CONCLUSIONS: MBL2 and FCN2 single or combined deficiencies are associated with increased duration of FN episodes as well as increased number of bacterial infections in children with B-ALL suggesting a prognostic role of these genes.

FcγRIIa and FcγRIIIa polymorphisms in childhood primary immune thrombocytopenia: implications for disease pathogenesis and outcome.

Primary immune thrombocytopenia (ITP) is the commonest acquired cause of bleeding in childhood. The aim of the present study was to evaluate the role of FcγRIIa and FcγRIIIa polymorphisms in the pathogenesis and therapeutic result of childhood ITP. The genotypic frequencies for two Fcγ receptor single-nucleotide polymorphisms, FcγRIIa-131 arginine (R) versus histidine (H) and FcγRIIIa-158 valine (V) versus phenylalanine (F) were examined in 53 children diagnosed with ITP. The genotype frequencies were compared with those of 45 healthy controls. The association between the above frequencies and disease natural course as well as therapeutic result following intravenous immunoglobulin (IVIG) administration was investigated. FcγRIIIa-158V was significantly overrepresented in children with ITP versus controls (P = 0.029), whereas no statistically significant difference was noted in FcγRIIa polymorphism distribution. No statistically significant difference was noted in the above genotype frequencies' distribution between children with newly diagnosed and chronic ITP, as well as with regards to the therapeutic result following IVIG administration. High-affinity FcγRIIIa variant (158 V) is possibly implicated in disease susceptibility, but neither of the two Fcγ receptor single-nucleotide polymorphisms seem to have any impact on chronicity or therapeutic effect of IVIG.

Adiponectin gene polymorphisms in obese Greek youth.

We investigated single nucleotide polymorphisms 45T --> G and 276G --> T of the adiponectin gene in 48 obese Greek children and adolescents (3.58-16.25 years old) and examined their association with adiponectin levels and insulin resistance (IR), estimated with HOMA-IR, AUC(insulin) and WBISI. The polymorphisms were: 45T/G in 13/48 (27%) and 45G/G in 2 (4%) individuals; 276G/T in 21/41 (51%) and 276T/T in 3 (8%) individuals. Adiponectin in carriers of one or two G-alleles at position 45 was comparable to 45T/T (10.11 +/- 6.19 vs 8.03 +/- 4.96 microg/ml). Adiponectin in carriers of one or two T-alleles at position 276 was comparable to 276G/G (9.73 +/- 5.19 vs 7.77 +/- 5.65 microg/ml). SNP 45T --> G was not associated with IR. SNP276G --> T was associated with decreased risk for IR (OR = 3.05, 95% CI = 1.2384-11.13). In conclusion, SNPs 45T --> G and 276G --> T are common in obese young Greeks. SNP276G --> T might be protective against IR.

Lipid profile, low-density lipoprotein oxidation and ceruloplasmin in the progeny of families with a positive history of cardiovascular diseases and/or hyperlipidemia.

Fifty-eight healthy progeny (mean age +/- SD 13.9 +/- 7.9 years) of 39 families with a positive history for cardiovascular diseases ([CVD] n = 44) or hyperlipidemia (n = 14) were included in the study and were compared with 30 age-matched control participants, with a negative family history, to evaluate lipid profile, ceruloplasmin (Cp), and lipid peroxidation product (malondialdehyde [MDA]) levels, as well as in vitro copper-induced Low-density lipoprotein (LDL) oxidizability. Mean serum levels of total cholesterol, LDL cholesterol (LDL-C), apolipoprotein B-100, and MDA of the participants were significantly higher than those of the controls. Lag time, an LDL resistance oxidation marker, was lower in the study group and negatively correlated with LDL-C (r = -.437, P < .05) and Cp (r = -.272, P < .05) serum levels. In conclusion, progeny with a positive family history for CVD or hyperlipidemia have an atherogenic lipid profile and increased LDL susceptibility to oxidation. High Cp levels seem to be related to lower resistance of LDL to oxidation.

Physical training in patients on hemodialysis has a beneficial effect on the levels of eicosanoid hormone-like substances.

OBJECTIVE: The aim of this study was to evaluate the changes in the levels of vasoactive eicosanoid hormone-like substances PGE2, PGI2 and TXA2 in hemodialysis (HD)patients who were following a long-term physical training program during the hemodialysis session. DESIGN: A total of 50 patients with Chronic Kidney Disease (CKD) (stage 5)on hemodialysis and 35 healthy individuals who served as controls (C) were evaluated. The 50 CKD patients were divided into two groups: the HD group consisted of 31 patients who received usual care without any physical activity during the hemodialysis sessions, while group HD/Exer included 19 patients who followed a program of physical exercise for six months. Plasma levels of PGE2, 6-Keto-PGF1alpha (the stable derivative of PGI2) and TXB2 (the stable derivative of TXA2) were measured by reliable enzymo-immunoassay methods (EIA) in HD and HD/Exer patients before and after the hemodialysis sessions as well as in the group of C. RESULTS: The plasma levels of PGE2 and 6-keto-PGF1alpha in group HD Exer/before patients were higher than those in group HDbefore (20.39+/-5.82 and 1449.19+/-553.41 vs 17.68+/-5.36 and 1295.10+/-384.43 pg/ml, p=0.044 and p=0.067, respectively), while the plasma levels of TXB2 were lower in HD Exer/before patients compared to HDbefore(499.76+/-67.51 vs 608.01+/-80.23 pg/ml, p=0.041). The plasma levels of PGE2 and 6-keto-PGF1alpha in group HD Exer/after patients were significantly higher compared to those in HDafter patients (23.01+/-5.70 and 1618.19+/-435.07 vs 16.57+/-4.97 and 1005.44+/-317.16 pg/ml, p<0.001 and p<0.040, respectively). However, significantly lower values in the plasma levels of TXB2 in HD Exer/after compared to HDafter patients (363.10+/-51.91 vs 439.75+/-62.34 pg/ml, p=0.030) were detected. As expected, PGE2 and 6-keto-PGF1alpha values were lower in C than in the groups of patients with CKD. CONCLUSIONS: The data indicate that exercise training during HD exerts a beneficial effect on the levels of the vasoactive eicosanoid hormone-like substances in patients on HD.

Adiponectin and insulin resistance in childhood obesity.

OBJECTIVES: To measure adiponectin serum levels in Greek children and adolescents and correlate them with body fat and insulin resistance. PATIENTS AND METHODS: Forty-six obese prepubertal children (19 M, 27 F) and 34 obese adolescents (17 M, 17 F) ages 9.33 +/- 1.57 and 13.6 +/- 1.42 years, respectively, and 43 matched control individuals were studied. Body mass index standard deviation score and percent body fat were measured by bioelectric impedance analysis. Fasting indices of insulin resistance (HOMA-IR and fasting glucose-to-insulin ratio) were calculated for all participants. Indices of insulin resistance derived from oral glucose tolerance tests were estimated in obese participants. Adiponectin was measured by enzyme-linked immunosorbent assay. RESULTS: (MEAN +/- SD):: Adiponectin serum levels were significantly lower in obese participants than in nonobese participants (8.11 +/- 3.80 vs 11.81 +/- 4.98 microg/mL, P < 0.001), in obese children than in nonobese children (8.86 +/- 3.86 vs 13.08 +/- 5.48 microg/mL, P < 0.001), in obese adolescents than in nonobese adolescents (7.04 +/- 3.43 vs 10.47 +/- 4.10 microg/mL, P = 0.002), and in obese adolescent boys than in obese adolescent girls (5.87 +/- 3.52 vs 8.31 +/- 3.16 microg/mL, P = 0.042). There were significant correlations between adiponectin and age, body mass index, body mass index standard deviation score, homeostasis model assessment for insulin resistance, and fasting glucose-to-insulin ratio. Adiponectin correlated with percent body fat after adjustment for sex. Adiponectin correlated significantly with several indices of insulin resistance, such as the areas under the curves for glucose and insulin, whole-body insulin sensitivity index, glucose 120', and insulin 30', in obese participants. CONCLUSIONS: Adiponectin was significantly lower in obese participants than in nonobese participants in general, and it correlated significantly with fasting indices of insulin resistance and with indices derived from oral glucose tolerance tests. It is worthwhile to further investigate the option of applying a simple measurement of serum adiponectin as a screening tool before applying more time-consuming techniques in young obese individuals.

Increase in oxidative stress but not in antioxidant capacity with advancing stages of chronic kidney disease.

BACKGROUND/AIMS: Increased oxidative stress in chronic kidney disease (CKD) was suggested to be both a cause and an effect of renal injury. However, the evolution of oxidant stress from early stages of renal function decline is not fully clear. This study aimed to determine the oxidant-antioxidant balance across the whole range of renal function. METHODS: A total of 116 patients with CKD (85 predialysis patients divided into groups according to CKD stage, and 31 patients with end-stage renal disease (ESRD) on hemodialysis treatment), as well as 29 healthy subjects were evaluated. Plasma levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP), a valid marker of oxidant stress, as well as total antioxidant capacity (TAC) and serum levels of vitamin E were measured in all participants. RESULTS: Plasma 15-F(2t)-IsoP levels were higher in predialysis and ESRD patients compared to healthy subjects and were progressively increasing with advancing CKD stages (p < 0.001). In contrast, plasma TAC was similar between healthy subjects and predialysis patients, and presented a small reduction in ESRD patients (p < 0.001). Vitamin E levels were higher in healthy subjects compared to any other group (p < 0.001) and slightly higher in ESRD patients compared to predialysis patients (p < 0.01), but did not differ significantly between the groups of predialysis patients. Plasma 15-F(2t)-IsoP levels were inversely correlated with estimated glomerular filtration rate in predialysis patients (r = -0.65, p < 0.001). CONCLUSIONS: This study shows that 15-F(2t)-IsoP levels increase progressively with advancing CKD stages, whereas TAC and vitamin E levels remain rather stable with the loss of renal function and change only in patients with ESRD.

The effect of anastrazole on symptomatic uterine leiomyomata.

OBJECTIVE: To evaluate the effect of anastrazole on symptomatic uterine leiomyomata. METHODS: This was a prospective intervention study carried out in a university department of obstetrics and gynecology. Forty-one premenopausal women eligible for hysterectomy with 45 uterine leiomyomata were enrolled and treated with anastrazole 1 mg daily for three cycles of 28 days each. The effect of treatment was evaluated on leiomyoma and uterine volumes, endometrial thickness, gonadotrophins, estradiol and hematocrit levels, menstrual pattern, severity of leiomyoma-related symptoms, and adverse effects. The effects of leiomyoma location, size, and age of participants on tumor volume changes were evaluated. RESULTS: Thirty-five women with 39 leiomyomata finished the study. Anastrazole resulted in a mean 55.7% reduction of leiomyoma volumes (163 mL to 72 mL, P<.001), a 29.9% reduction in total uterine volumes (278 mL to 195 mL, P<.001), and an 11.3% increase of the hematocrit levels (33.4% to 37.2%, P<.001) at the end of the treatment. Leiomyoma location had no significant effect on volume decrease. Leiomyoma volume decreased in women aged older than 40 years (P=.002), whereas no difference was found in women younger than 40. The size of large (greater than 50 mm) leiomyomata decreased significantly (P=.004). Less difference was observed in small (50 mm or less) leiomyomata (P=.031). No differences were detected in hormonal status. Anastrazole improved leiomyoma-related symptomatology and caused no serious adverse effects. CONCLUSION: In premenopausal women, anastrazole reduces the size of uterine leiomyomata, improves symptomatology, and is generally well tolerated. LEVEL OF EVIDENCE: III.