PlGF and sFlt-1 levels in patients with non-transfusion-dependent thalassemia: Correlations with markers of iron burden and endothelial dysfunction.

BACKGROUND: Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT). PATIENTS AND METHODS: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls. RESULTS: Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P < .001), sFlt-1/PlGF (2 vs 4.7, P < .001), and vWF:antigen (88 vs 77.1 IU/dL, P < .01). There was a strong correlation of ferritin with PlGF (r = .653, P < .001) and with vWF:antigen (r = .503, P = .003). CONCLUSIONS: In this study, we demonstrated an association between increased PlGF and iron overload and the degree of tissue hypoxia in patients with NTDT. High vWF:antigen expressing endothelial damage may be associated with specific NTDT comorbidities.

Adhesion molecules and high-sensitivity C-reactive protein levels in patients with sickle cell beta-thalassaemia.

BACKGROUND AND AIM: The primary symptoms of sickle cell disease (SCD) arise from vaso-occlusive crises. The pathogenesis of these crises is complex phenomenon where endothelial activation and damage has a major role. Chronic inflammation also plays an important role in the pathophysiology of SCD. We aimed to investigate endothelial activation in Caucasian Greek patients with SCD by means of measuring adhesion molecules and markers of inflammation. SUBJECTS AND METHODS: Twenty-eight patients with SCD aged 5-63 years were included in the study. Most of the patients (23/28) were double heterozygotes for sickle cell/beta-thalassaemia, while five patients (5/28) were sickle cell homozygotes. Patients were treated with one/or more of hydroxyurea, therapeutic phlebotomies, blood transfusion or splenectomy. Twenty apparently healthy individuals matched for age and sex formed the control group. Measurements of soluble intercellular adhesion molecule-1, (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), P-selectin, E-selectin, soluble thrombomodulin (sTM) and high-sensitivity C-reactive protein (hs-CRP) levels were performed using immunoassays in both patients and healthy individuals. RESULTS: We found that all endothelial adhesion molecules and hs-CRP were significantly increased (P < 0·001) in patients with SCD compared with controls, while sTM levels did not differ significantly (P > 0·05) and this increase was not influenced by the treatment. CONCLUSION: Our findings demonstrate the high degree of endothelial activation and damage seen in sickle cell patients even in steady-state condition, as well as the important chronic inflammation underlying the pathophysiology of this widespread disease.

Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status.

Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A, C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p<0.00001), GSH(reduced) (p<0.00001) and GSSG (p>0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p<0.00001), while antioxidant defense expressed as FORD was significantly reduced (p<0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status.

Disturbances of biomarkers of iron and oxidant-antioxidant homeostasis in patients with beta-thalassemia intermedia.

BACKGROUND: Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI. OBJECTIVES: To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. DESIGN: Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. RESULTS: Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p〈0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThI patients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI. CONCLUSIONS: Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.

Acute resistance exercise results in catecholaminergic rather than hypothalamic-pituitary-adrenal axis stimulation during exercise in young men.

Exercise is a paradigm of a stress situation. The adaptive response to stressors comprises the activation of the hypothalamic-pituitary-adrenal (HPA) axis and components of the autonomic sympathetic system. An aseptic inflammatory reaction is triggered by exercise, involving the stimulation of the so-called proinflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and IL-6. The anti-inflammatory cytokines IL-2, IL-8, and IL-10 increase moderately during resistance exercise. To investigate the effect of a short bout of resistance exercise on components of the stress and inflammatory responses during the exercise period, 17 healthy, young, untrained male volunteers were studied during 3 equal consecutive cycles of resistance exercises of 30 min total duration. Blood sampling was performed at baseline and at the end of each cycle. Lactate, cortisol, catecholamines (epinephrine, norepinephrine), IL-1α, IL-1ß, IL-2, IL-6, IL-8, IL-10, epidermal growth factor (EGF), and monocyte chemotactic protein-1 (MCP-1) were measured at all time-points. Circulating levels of catecholamines and lactate increased significantly (P < 0.05) whereas cortisol did not. During the time course of the exercise, circulating levels of TNFα, IL-2, and EGF increased, whereas MCP-1 decreased significantly. IL-1α, IL-1ß, IL-6, IL-8, and IL-10 levels did not change significantly. Statistically significant positive linear correlations were found between areas under the curve for increases in levels of IL-2 and TNFα, TNFα and cortisol, as well as epinephrine and norepinephrine. We conclude that acute resistance exercise results in catecholaminergic, but not HPA axis stimulation during exercise, in parallel with a mild inflammatory reaction. The absence of a major inflammatory reaction and of a cortisol increase during acute resistance exercise makes this a good candidate for the exercise of sedentary individuals.

Nitric oxide, ammonia, and CRP levels in cirrhotic patients with hepatic encephalopathy: is there a connection?

GOALS: Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice. BACKGROUND: HE is a neuropsychiatric complication of cirrhosis. The exact pathogenetic mechanisms underlying the presence of HE are not known. However, dysfunction of the NO pathway and ammonia detoxification are thought to play a major role. STUDY: Sixty-seven cirrhotic patients, 36 (53.7%) without HE, and 31 (46.3%) with HE were included in the study. Eighteen healthy individuals were used as control group. Clinical and laboratory data, including ammonia and stable end products of NO using Griess reaction, were collected. RESULTS: NOx levels were statistically significantly higher in cirrhotic patients (225.5 µmol/L) than in control group [(67.94 µmol/L) (P=0.000)]. NOx levels were, also, statistically significantly higher in patients with HE compared with patients without HE (324.67 µmol/L vs. 141.96 µmol/L, P=0.000). Significant correlation between the presence of HE and NOx, ammonia, C-reactive protein, albumin, Model for End-Stage Liver Disease score, and Child-Pugh classification revealed. NOx levels also correlated with severity of HE. NOx and ammonia are independent factors predicting HE according to regression analysis. Diagnostic accuracy for the diagnosis of HE using a combination of NOx and ammonia was superior compared with standalone NOx or ammonia utilization. CONCLUSIONS: NOx levels are correlated with the presence and severity of HE. NOx levels determination, in addition to ammonia levels, could contribute in diagnosis of HE.

Soluble endothelial adhesion molecules and inflammation markers in patients with beta-thalassemia intermedia.

The term thalassemia intermedia, indicates a clinical condition of intermediate severity between thalassaemia minor, the asymptomatic carrier, and thalassaemia major, the transfusion-dependent, severe form. Thromboembolic events frequently complicate the outcome of thalassemia intermedia patients, reflecting a hypercoagulable state to which endothelial activation is believed to play an important role. The aim of this study was to evaluate the levels of soluble endothelial adhesion molecules that reflect endothelial activation and dysfunction and levels of chronic inflammation markers in the serum of beta-thalassemia intermedia patients. Thirty-five Greek patients with beta-thalassemia intermedia that have received different types of treatment (Hydroxyurea, splenectomy, untreated), aged 8-63 years, were included in the study. Twenty apparently healthy individuals matched for age and sex, formed the control group. Measurements of sVCAM-1, sICAM-1, sTM, P-selectin, E-selectin and CRP levels were performed using immunoassays. We found that all endothelial adhesion molecules and CRP were significantly increased in patients (p<0.001) and not influenced by treatment. A negative correlation was observed between levels of sICAM-1 and sTM and this finding agrees with the results of studies, which propose this correlation as a predictive marker of increased risk for vascular damage. No correlation was observed between endothelial adhesion molecules and inflammation markers. These findings support the hypothesis that a serious degree of endothelial activation and damage along with a state of chronic inflammation underlie the pathophysiology of beta-thalassemia intermedia. Furthermore, these findings are of particular importance in patients who can otherwise be characterized by a subtle clinical phenotype and may have an important role in their clinical care.

A favorable metabolic and antiatherogenic profile in carriers of CYP21A2 gene mutations supports the theory of a survival advantage in this population.

CONTEXT: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The 'mediators' of such an effect remain speculative. OBJECTIVE: To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers. It is anticipated that by studying atherogenic risk factors at such an early developmental stage, age-related alterations in these factors may be minimized. METHODS: The study group included 45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not differ in chronological age, age at pubarche or menarche, pubertal stage, body mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as well as markers of endothelial dysfunction were determined by appropriate methodology. Additionally, in each subject, an oral glucose tolerance test and a gonadotrophin-releasing hormone GnRH analogue stimulation test were carried out. RESULTS: Endothelin-1 values were lower in the carriers compared to the noncarriers (p = 0.031). Higher tissue plasminogen activator and lower plasminogen activator inhibitor-1 values were found in carriers compared to noncarriers (p = 0.02 and <0.001, respectively). The ratio of the insulinogenic index/homeostasis model assessment for insulin resistance, which reflects beta-cell function, was higher in carriers (p = 0.048), indicating a more favorable beta-cell function in the carriers. CONCLUSIONS: Our findings that carriers of CYP21A2 gene mutations have a more favorable internal milieu with regard to the metabolic syndrome and atherogenesis support the theory that heterozygous CYP21A2 mutations provide a survival advantage. The mechanisms involved may be related to the insulin secretion-action pathway, hypothalamic-pituitary-adrenal axis responsiveness or other still unrecognized factors.

The natural history of neuroendocrine changes in pediatric posttraumatic stress disorder (PTSD) after motor vehicle accidents: progressive divergence of noradrenaline and cortisol concentrations over time.

BACKGROUND: The hypothalamic-pituitary-adrenal axis and the catecholaminergic system are involved in the pathophysiology of post-traumatic stress disorder (PTSD). This was a prospective and longitudinal study of neuroendocrine physiology in children with PTSD following a motor vehicle accident (MVA). METHODS: Sixty children aged 7-18 were studied immediately after an MVA and 1 and 6 months later. Fasting morning plasma catecholamine and serum cortisol concentrations were measured. Salivary cortisol concentrations were measured serially five times daily to examine circadian variation in all three assessments. Values were compared between those who did (PTSD) or did not develop PTSD (non-PTSD) after the trauma and a control group at months 1 and 6. RESULTS: Twenty-three of the children had PTSD at the 1-month and 9 children at the 6-month evaluations. 1) Plasma noradrenaline concentrations were higher in the PTSD group than in the other two groups at both months 1 and 6 (p = .001 and p = .001, respectively). Additionally, the PTSD patients presented with significantly higher salivary cortisol concentrations at 18.00 (p = .03) and 21.00 (p = .04) at month 1.2) Eight children suffering from PTSD at both months 1 and 6 had significantly elevated plasma noradrenaline concentrations at month 6 compared with those at month 1 and at baseline and to the other two groups (within subjects: p < .001; between subjects: p = .005). The initially elevated evening salivary cortisol concentrations in this group normalized at month 6. CONCLUSIONS: This progressive divergence of noradrenaline and cortisol concentrations over time might underlie the natural history and pathophysiology of PTSD.

Elevated morning serum interleukin (IL)-6 or evening salivary cortisol concentrations predict posttraumatic stress disorder in children and adolescents six months after a motor vehicle accident.

BACKGROUND: This study examined prospectively the activity of the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system and inflammatory factors in children shortly after a motor vehicle accident (MVA) in relation to later posttraumatic stress disorder (PTSD) development. PATIENTS AND METHODS: Fifty six children, aged 7-18, were studied after an MVA and 1 and 6 months later; 40 subjects served as controls. Morning serum cortisol and interleukin (IL)-6 and plasma catecholamine concentrations were measured within 24h after the event. Salivary cortisol was measured 5 times at defined time points during the same day. PTSD diagnoses 1 and 6 months later were based on K-SADS interview. RESULTS: Morning serum IL-6 concentrations, measured within the first 24h after the accident, were higher in children that developed PTSD 6 months later than those who did not and those of the control group. Longitudinal IL-6 measurements revealed normalization of IL-6 in the PTSD group, while no differences between the three groups were detected 1 and 6 months later. Evening salivary cortisol and morning serum IL-6 after the accident were positively inter-related (r=0.54, p<0.001) and in separate regression analyses both predicted PTSD development 6 months later. In contrast, morning serum IL-6 did nor correlate with morning serum or salivary cortisol concentrations. CONCLUSIONS: Immediate posttraumatic alterations in neuroendocrine or inflammatory factors-increased evening salivary cortisol and/or increased morning serum IL-6 concentrations-are involved in subsequent PTSD development in children and adolescents.

Longitudinal course and clinical significance of TGF-beta1, sL- and sE-Selectins and sICAM-1 levels during severe acute stress in children.

OBJECTIVES: To elucidate the potential role of circulating levels of transforming growth factor-beta1 (TGF-beta1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L- and sE-Selectins (sL- and sE-Selectins) in children with sepsis, traumatic brain injury (TBI) or acute respiratory distress syndrome (ARDS). DESIGN AND METHODS: Levels of TGF-beta1, sICAM-1, L- and sE-Selectins were determined using solid-phase sandwich enzyme-linked immunosorbent assay in plasma of 10 patients with sepsis, 10 patients with TBI, 10 patients with ARDS, compared to 10 ventilated controls with chronic illness but not in acute stress, on days 1, 3, 5, 7 and 10. RESULTS: The highest values of sICAM-1 were observed in patients with TBI (p<0.001) and those of sE-Selectin in patients with sepsis (p=0.0001). Patients in the control group did not show an elevation of sE-Selectin and sICAM-1 levels longitudinally. Increased levels of measured molecules (TGF-beta1, p<0.02, sE-Selectin, p<0.02, sL-Selectin, p=0.06, sICAM-1, p<0.03) were demonstrated among survivors in the sepsis and ARDS groups of patients and were positively correlated with length of stay (p<0.04) and mechanical ventilation (p<0.001). CONCLUSIONS: A sustained increase of adhesion molecules occurs during acute stress in children which may contribute to morbidity in patients with sepsis (sE-Selectin) or traumatic brain injury (sICAM-1). Suppression of the expected response of sE-Selectins, s-ICAM-1 and TGF-beta1 is associated with poor outcome.

Maternal-neonatal serum paraoxonase 1 activity in relation to the mode of delivery.

AIM: To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS) and the paraoxonase 1 (PON 1) serum activity in mothers and their newborns. SUBJECTS AND METHODS: One hundred six women with normal pregnancy were divided into 4 groups: group A (n = 28) with normal labour and vaginal delivery (VG), group B (n = 25) with scheduled caesarean section (CS), group C (n = 26) with "emergency" CS and group D (n = 27) with prolonged labour + VG. Blood was obtained from the mothers at the beginning of the labour process and immediately after delivery (pre- and post-delivery) as well as from the umbilical cord (CB). PON 1 activity and blood chemistry were determined using the Bayer Advia 1650 Clinical Chemistry System, whereas TAS levels were measured spectrophotometrically at 450 min in microtiter plates. RESULTS: TAS levels were similar pre-delivery and low in CB in all the groups. In contrast, TAS levels were remarkably reduced in group C and in group D post-delivery whereas they were nearly unchanged in group B and just lowered in group A, at the same time of study. PON 1 activity was practically unaltered in group A and group B pre- vs. post-delivery. Interestingly, the enzyme activity was remarkably decreased in group C (222 +/- 16 vs. 153 +/- 14 U/min/mL) and group D (216 +/- 16 vs. 135 +/- 15 U/min/mL, p < 0.001) as compared with those of the other groups at the same time of study. Additionally, PON 1 activity was higher in the newborns of group A and group B than those in group C and group D. TAS and HDL positively correlated with PON 1 activity. CONCLUSION: The low TAS levels and the decreased PON 1 activity, which were found in groups C and D post-delivery, may be due to the increased production of free radicals, during long-lasting labour + VG and obstructive labour + CS. PON 1 activity was low in CB irrespectively of the mode of delivery, probably due to the low lipid levels in the serum of the umbilical cord. Neonates born with normal delivery or scheduled CS are benefited with a higher antiatherogenic enzyme activity perinatally.

Valproic acid monotherapy induces DNA oxidative damage.

Valproic acid (VPA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) are implicated with the free radicals production. We aimed to evaluate total oxidant status (TOS) and 8-OHdG in children on VPA monotherapy. Fifty patients with seizures, mean age 8.5+/-3.6 years, were divided into group A (N=26) and group B (N=24) with VPA serum levels 81.0+/-8.0 and 114+/-9.7 microg/mL, respectively. Thirty healthy children were the controls. Liver function tests and lipids were determined with routine methods, TOS and 8-OHdG with commercial kits, after 60 days on VPA therapy. Liver function parameters, lipids, TOS (647+/-43 micromol/L) and 8-OHdG (0.49+/-0.08 ng/mL) were significantly higher in group B than those in group A (580+/-40 micromol/L, 0.37+/-0.04 ng/mL, p<0.001) and controls (124+/-30 micromol/L, 0.11+/-0.04 ng/mL, p<0.001, respectively). Significant correlation coefficients were found between 8-OHdG versus TOS (r=0.67, p<0.001) and 8-OHdG versus VPA (r=0.60, p<0.001) levels. It is suggested that VPA impairs the liver function resulting in free radicals production. The latter seems to produce DNA oxidative damage in liver cells, not excluding neuronal cells, as evidenced by the measured remarkably increased 8-OHdG serum levels. 8-OHdG evaluation may be a useful biomarker to follow up the increased risk of degeneration process in VPA patients.

Circulating levels of KL-6 in acute respiratory distress syndrome sepsis or traumatic brain injury in critically ill children.

KL-6 is a high molecular weight glycoprotein that is expressed on the apical borders of normal secretary alveolar epithelial cells. The aim of our study was to elucidate the potential role of circulating levels of KL-6, related to C-reacting protein (CRP), disease severity (PRISM, TISS), length of stay (LOS) or mechanical ventilation (LOMV), and outcome, in children with acute respiratory distress syndrome (ARDS), sepsis, or traumatic brain injury (TBI). KL-6 concentrations were monitored using solid phase sandwich enzyme-linked immunosorbent assay in plasma of nine patients with ARDS and compared to nine patients with TBI, nine with sepsis, and nine ventilated patients with cancer of matched illness severity on days 1, 3, 5, 7, and 10. Initial respiratory/ventilatory parameters (oxygenation index, plateau pressures) were recorded for ARDS patients. Patients with ARDS had higher early plasma levels of KL-6 (956 +/- 400 U/ml), as compared to patients with TBI (169 +/- 9 U/ml), sepsis (282 +/- 81 U/ml), and ventilated controls (255 +/- 40 U/ml). Significant correlations were demonstrated between plasma KL-6 concentration and oxygenation index, PaO(2): FiO(2) ratio, LOS and LOMV, but not with CRP or PRISM. Only in patients with ARDS, plasma KL-6 levels were higher in non-survivors than survivors (P < 0.03). Plasma KL-6 levels have possible prognostic significance and may provide a useful marker for ARDS in critically ill children.

Plasma soluble α-klotho protein levels in premature and term neonates: correlations with growth and metabolic parameters.

OBJECTIVE: α-Klotho (α-KL), a protein with antiaging properties, regulates phosphate, calcium, and bone metabolism, induces resistance to oxidative stress, and may participate in insulin signaling. The role of α-KL in neonates, known to be prone to metabolic disturbances and oxidative stress, is not known. The aim of this study was to evaluate circulating soluble α-KL concentrations in preterm and full-term neonates and unravel possible correlations with growth, metabolism, and indices of oxidative stress. DESIGN: Prospective study. METHODS: Plasma-soluble α-KL levels were determined by specific ELISA in 50 healthy neonates (25 preterm, mean (s.d.) gestational age (GA) 33.7 (1.1) weeks, and 25 full-term infants) at days 14 and 28 of life. Associations of α-KL with anthropometric, metabolic parameters, and indices of oxidative stress were examined. RESULTS: α-KL levels were significantly higher in full-term than in preterm infants at both days 14 (1099 (480) pg/ml vs 884 (239) pg/ml respectively; P<0.05) and 28 (1277 (444) pg/ml vs 983 (264) pg/ml respectively; P<0.01). In both preterm and full-term infants, α-KL levels increased significantly from day 14 to 28 of life (P<0.001). Circulating α-KL concentrations correlated with GA (ß=0.32, P=0.001), body weight (ß=0.34, P=0.001), body length (ß=0.33, P=0.001), 1,25-dihydroxy-vitamin D level (ß=0.24, P<0.05), and malondialdehyde level (ß=0.20, P<0.05) but not with glucose, insulin, or homeostasis model assessment index of insulin resistance values. CONCLUSIONS: Soluble α-KL levels rise as GA and postnatal age advance in neonates and may have an impact on vitamin D metabolism and oxidative stress. Whether α-KL may have a role in the regulation of infants' growth should be further studied.

Elevated coagulation and inflammatory markers in adolescents with a history of premature adrenarche.

Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P = .0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P = .0001) and plasminogen activator inhibitor 1 (r = 0.36, P = .04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P = .02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities.

Circulating adiponectin in preterm infants fed long-chain polyunsaturated fatty acids (LCPUFA)-supplemented formula--a randomized controlled study.

Adiponectin has potent insulin-sensitizing effects, improves lipid metabolism, and potentially protects against the development of metabolic syndrome. Thus, increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest. The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids (LCPUFA) on serum adiponectin and lipid concentrations in preterm infants. Adiponectin and lipid levels of 60 healthy preterm infants [gestational age 32.7 (1.9) wk] randomly assigned to be fed either 1) a formula containing LCPUFA [arachidonic and docosahexanoic] (+LCPUFA group) or 2) the same formula without LCPUFA (-LCPUFA/control group), were determined at mean (SD) 33.8 (11.7) d. Adiponectin and HDL-C concentrations were significantly higher in the +LCPUFA group than in controls (p = 0.002 and p = 0.01, respectively); whereas, triglyceride levels were lower (p = 0.06). Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the +LCPUFA group but not in the controls. In conclusion, circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile.

Adipose tissue lipolysis is upregulated in lean and obese men during acute resistance exercise.

OBJECTIVE: To investigate the effect of acute resistance exercise on adipose tissue triacylglycerol lipase activity (TGLA) in lean and obese men. RESEARCH DESIGN AND METHODS: Nine lean and eight obese men performed 30 min of circuit resistance exercise. Adipose tissue and blood were sampled during exercise for TGLA, metabolite, and hormone determinations. Respiratory exchange ratio (RER) was measured throughout exercise. RESULTS: Energy expenditure of exercise relative to body mass was higher in the lean and RER was higher in the obese men, suggesting lower fat oxidation. TGLA increased 18-fold at 5 min of exercise in the lean men and 16-fold at 10 min of exercise in the obese men. The delayed lipolytic activation in the obese men was reflected in serum nonesterified fatty acid and glycerol concentrations. Plasma insulin increased in the obese but did not change in the lean men. CONCLUSIONS: Resistance exercise upregulated adipose tissue lipolysis and enhanced energy expenditure in lean and obese men, with a delayed lipolytic activation in the obese men.

Oxidative stress in preterm infants fed a formula containing long-chain polyunsaturated fatty acids (LCPUFA).

Our study examined if dietary long-chain polyunsaturated fatty acids (LCPUFA) have an impact on oxidative stress in preterm infants. Serum malonyldialdehyde (MDA), total peroxide concentrations, and total antioxidant capacity were determined at mean (standard deviation [SD]) 34.7 (10.9) days of life in 104 healthy preterm infants (gestational age, 32.6 [2.9] weeks; birthweight; 1605 [285] g) who were randomly assigned to be fed since birth either a formula containing LCPUFA (arachidonic and docosahexaenoic) (group A, n = 50) or a LCPUFA-free formula with identical compositions for other nutrients (group B, n = 54). Clinical and anthropometric characteristics did not differ significantly between the two groups. Mean (SD) serum MDA levels did not differ significantly between groups A (0.23 [0.04] micromol/L) and B (0.22 [0.05] micromol/L). The concentrations of total peroxides were below the detection limits of the assay in 41 of 50 (82%) infants of group A and 43 of 54 (79%) infants of group B and not significantly different between the two infant groups. No difference was observed in serum total antioxidant capacity between groups A (340.0 [46.2] micromol/L) and B (354.7 [46.5] micromol/L). We concluded that supplementation of infant formulas with LCPUFA does not affect lipid peroxidation in healthy preterm infants.

Maternal-neonatal 8-hydroxy-deoxyguanosine serum concentrations as an index of DNA oxidation in association with the mode of labour and delivery.

AIM: To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS), and the biomarker of DNA oxidation, 8-hydroxy-deoxyguanosine (8-OHdG) serum levels, in mothers and their newborns. SUBJECTS AND METHODS: Some 106 women with normal pregnancy and normal blood biochemical parameters were divided into 4 groups: Group A (n=28) with normal labour and vaginal delivery (VG), Group B (n=25) with scheduled cesarean section (CS), Group C (n=26) with 'emergency' CS, and Group D (n=27) with prolonged labour+VG. Blood was obtained from the mothers at the beginning of labour, and immediately after delivery (pre- and post-delivery), as well as from the umbilical cord (CB). TAS, 8-OHdG and creatine kinase (CK) were measured in the sera with appropriate methodology. RESULTS: TAS levels were almost similar in all the groups pre-delivery, and in CB irrespective of the mode of labour and delivery, and remarkably decreased in Groups C and D post-delivery. 8-OHdG levels in Group C (0.94+/-0.08 ng/ml) and Group D (0.98+/-0.08 ng/ml) were significantly higher than those in Group A (0.26+/-0.01 ng/ml, p<0.001) and Group B (0.28+/-0.07 ng/ml, p<0.001) post-delivery. 8-OHdG levels were low in CB, independent of the mode of labour. CK positively correlated with 8-OHdG (r=0.48, p<0.001), the latter negatively correlated with TAS (r=-0.53, p<0.01). CONCLUSIONS: The lowest TAS and the highest 8-OHdG levels were found in Groups C and D post-delivery, probably due to the long-term participation of the mothers' skeletal and uterus muscles, whereas 8-OHdG levels were low in CB irrespective of the mode of delivery, possibly as a consequence of the antioxidant action of the placenta and/or the low lipid levels in the serum of the umbilical cord.