Seroepidemiology of SARS-CoV-2 in pediatric population during a 16-month period prior to vaccination.

Limited prospective serosurveillance data in children regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We prospectively investigated SARS-CoV-2 seropositivity in children during a 16-month period of the coronavirus disease 2019 (COVID-19) pandemic, including the four waves of the pandemic, before SARS-CoV-2 adolescents' vaccination. Serum samples from children admitted to the major tertiary Greek pediatric hospital for any cause, except for COVID-19 infection, were randomly collected from 05/2020 to 08/2021. The study period was divided into four 4-month periods representing relevant epidemic waves. Total SARS-CoV-2 antibodies for nucleocapsid protein were determined using the Elecsys® Anti-SARS-CoV-2 reagent. A total of 3099 children (0-16 years) were included in the study. A total of 344 (11.1%) seropositive children were detected (males: 205 [59.5%]; median age [interquartile range [IQR]]: 3 years [0.6-10]). Seropositivity rates (%) increased during the four 4-month periods: 1.4%, 8.6%, 17.2%, and 17.6%, respectively. A correlation of seropositivity rates in children with new diagnosed SARS-CoV-2 cases in the community was detected. No significant differences were detected between males and females. Seropositivity was significantly higher in hospitalized than in nonhospitalized children and in non-Greek compared to Greek children (p < 0.001). The lowest seropositivity rate before school opening (9/2021) was detected in the age groups 6-12 years (14.4%) and 12-16 years (16.1%). However, compared with the other age groups, the lowest median antibody titers were observed in children 0-1 year (median [IQR]: 13.9 cut-off index: [4.5-53.9] [p < 0.001]). Although the seropositivity of children was related to the community epidemic waves, the exposure was limited. Low seropositivity rates in school-age children support the need for SARS-CoV-2 immunization.

SARS-CoV-2 seroepidemiology in paediatric population during Delta and Omicron predominance.

Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0-16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24-144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0-1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12-16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12-16 years [32.2 COI (7-77.1) vs. 11.4 COI(2.8-50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.

The Growth Differentiation Factor-15 (GDF-15) levels are increased in patients with compound heterozygous sickle cell and beta-thalassemia (HbS/ßthal), correlate with markers of hemolysis, iron burden, coagulation, endothelial dysfunction and pulmonary hypertension.

The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. GDF-15, a multifactorial cytokine, is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury, while high levels of serum GDF-15 associate with ineffective erythropoiesis and may reflect a certain type of bone marrow stress or erythroblast apoptosis. In this context we aimed to evaluate GDF-15 levels in 89 patients with HbS/ßthal at steady phase and in 20 apparently healthy individuals, and correlate with clinical features of the disease and markers of hemolysis, iron burden, inflammation, coagulation and endothelial dysfunction. We found that: GDF-15 levels were elevated in patients with HbS/ßthal compared to controls (1980.7 ±â€¯159.8 vs 665.4 ±â€¯50.9 pg/mL, p < 0.0001) and correlated significantly with LDH (p < 0.001), Hepcidin-25/Ferritin molar ratio (p = 0.002), vWF:antigen (p < 0.05), HbA% (p < 0.001) and Mean Pulmonary Artery Pressure (p < 0.001). These findings demonstrate for first time an important multifactorial role of GDF-15 in patients with HbS/ßthal, however, prior to its clinical usefulness, this biomarker must undergo through rigorous validation in multiple cohorts.

Association between Brain-Derived Neurotrophic Factor (BDNF) Levels in 2nd Trimester Amniotic Fluid and Fetal Development.

The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid were collected from women who had undergone amniocentesis early in the 2nd trimester. All pregnancies were followed up until delivery and fetal growth patterns and birth weights were recorded, following which pregnancies were divided into three groups based on fetal weight: (1) AGA (appropriate for gestational age), (2) SGA (small for gestational age), and (3) LGA (large for gestational age). We focused on these three groups representing a reflection of the intrauterine growth spectrum. Our results revealed the presence of notably higher BDNF levels in the amniotic fluid of impaired growth fetuses by comparison with those of normal growth. Both SGA and macrosomic fetuses are characterized by notably higher amniotic fluid levels of BDNF (mean values of 36,300 pg/ml and 35,700 pg/ml, respectively) compared to normal-growth fetuses (mean value of 32,700 pg/ml). Though apparently small, this difference is, nevertheless, statistically significant (p value < 0.05) in SGA fetuses in the extremes of the distribution, i.e., below the 3rd centile. In conclusion, there is clear evidence that severe impairment of fetal growth induces the increased production of fetal brain growth factor as an adaptive mechanism in reaction to a hostile intrauterine environment, thereby accelerating fetal brain development and maturation.

Assessment of serum bioactive hepcidin-25, soluble transferrin receptor and their ratio in predialysis patients: Correlation with the response to intravenous ferric carboxymaltose.

BACKGROUND: No reliable biomarker exists to predict responsiveness to intravenous (IV) iron (Fe) in iron deficient patients with CKD. We aimed to investigate the clinical value of bioactive Hepcidin-25 and soluble Transferrin Receptor (sTfR) levels in predialysis patients. PATIENTS AND METHODS: In this prospective study 78 stable stage III-IV CKD predialysis patients with (responders) (40 patients) and without (non-responders) (38 patients) adequate erythropoiesis after IV administration of ferric-carboxymaltose (FCM). Patients were divided in two groups according to their response to IV administration of ferric-carboxymaltose (FCM). Along with measurements of common hematologic and blood chemistry parameters, determinations of sTfR and bioactive Hepcidin-25 were performed. RESULTS: Hepcidin-25 levels were lower in the responders (p=0.025), while sTfR and sTfR/Hepcidin-25 ratio were higher (p<0.01 and p=0.002 respectively). Diagnostic efficacy indicated cut off point of 1.49 for Hepcidin-25 had sensitivity 84% and specificity 48%, while cut off point of 1.21 for sTfR/Hepcidin-25 ratio had sensitivity 82% and specificity 52% to predict correctly response to iron supplementation therapy. Furthermore, log sTfR/Hepcidin-25 correlated negatively with hs-CRP (p=0.005) and IL-6 (p<0.04) in non-responders, while such correlations were not found in responders (p>0.05). CONCLUSIONS: These results suggest that lower Hepcidin-25, as well as higher sTfR and sTfR/Hepcidin-25 ratio were significant predictors of favorable hemoglobin response within a month after IV administration of FCM in patients with CKD. Further experiments and clinical studies in other groups of patients are needed to better elucidate the role of Hepcidin-25 and sTfR/Hepcidin-25 ratio as predictors of response to intravenous iron administration.

Muscle damage, inflammatory, immune and performance responses to three football games in 1 week in competitive male players.

PURPOSE: We examined effects of a three-game, 1-week microcycle (G1, G2, G3) on recovery of performance and inflammatory responses in professional male footballers. METHODS: Players were randomized into an experimental (EXP; N = 20) and a control group (CON; N = 20). Blood was drawn and repeated sprint ability (RSA), muscle soreness and knee range of motion (KJRM) were determined pre- and post-games and during recovery. RESULTS: High-intensity running during G2 was 7-14% less compared to G1 and G3. RSA declined in EXP by 2-9% 3 days post-game with G2 causing the greatest performance impairment. In EXP, game play increased muscle soreness (~sevenfold) compared to CON with G2 inducing the greatest rise, while KJRM was attenuated post-game in EXP compared to CON (5-7%) and recovered slower post G2 and G3 than G1. CK, CRP, sVCAM-1, sP-Selectin and cortisol peaked 48 h post-games with G2 eliciting the greatest increase. Leukocyte count, testosterone, IL-1ß and IL6 responses, although altered 24 h post each game, were comparable among games. Plasma TBARS and protein carbonyls rose by ~50% post-games with G2 eliciting the greatest increase 48 h of recovery. Reduced to oxidized glutathione ratio declined for 24 h post all games with G2 displaying the slowest recovery. Total antioxidant capacity and glutathione peroxidase activity increased (9-56%) for 48 h in response to game play. CONCLUSION: In summary, post-game performance recovery and inflammatory adaptations in response to a three-game weekly microcycle displayed a different response pattern, with strong indications of a largest physiological stress and fatigue after the middle game that was preceded by only a 3-day recovery.

Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection.

BACKGROUND: Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known. METHODS: Plasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed. RESULTS: Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005). CONCLUSIONS: Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process.

Non-traditional adipokines in pediatric HIV-related lipodystrophy: a-FABP as a biomarker of central fat accumulation.

BACKGROUND: Lipodystrophy characterized by adipose tissue redistribution and lipid and glucose metabolism abnormalities, is common among HIV-infected adults and children on highly-active-antiretroviral-therapy (HAART). In a previous study of HIV-infected children, we did not detect insulin resistance, despite a high percentage of body fat redistribution abnormalities. AIM OF THE STUDY: To investigate the non-traditional adipokines Retinol-binding-Protein-4 (RBP4), neutrophil-gelatinase-associated-lipocalin (NGAL), a-Fatty-Acid-Binding-Protein (a-FABP) and YKL-40 in HIV-infected children on highly-active-antiretroviral-therapy and evaluate their possible association to lipodystrophic changes or insulin resistance. METHODS: Seventeen vertically HIV-infected children (mean age: 12.5 years, mean duration of HAART: 5.2 years) and 20 age- and BMI-matched controls were recruited. The HIV-children were re-evaluated after 12 months. RBP4, NGAL, a-FABP and YKL-40 were assessed at study entry and 12 months later and were correlated to body fat content and insulin resistance. RESULTS: RBP4 values were similar at study entry and 12 months later in HIV-children and controls and showed no correlation to body fat or insulin resistance. NGAL was lower in HIV children at study entry but normalized after 12 months with no positive correlation to insulin resistance. a-FABP was positively correlated to body fat content, especially to trunk fat, both at initial evaluation and at follow-up in HIV children and, after prolonged highly-active-antiretroviral-therapy, it was also positively correlated to insulin resistance. CONCLUSIONS: This study is the first one to demonstrate that a-FABP could be a useful marker in unraveling central fat accumulation in HIV-infected children on highly-active-antiretroviral-therapy. Large prospective studies are needed to confirm these results.

Clinical value of plasma soluble urokinase-type plasminogen activator receptor levels in term neonates with infection or sepsis: a prospective study.

BACKGROUND: suPAR, the soluble form of the urokinase-type plasminogen activator receptor, has been identified as a biomarker of infection in adults but its properties in neonatal infection are not known. METHODS: Plasma suPAR levels were determined by ELISA in 47 term neonates with infection (19 bacterial and 28 viral) and in 18 healthy neonates as controls. Thirteen out of 47 infected neonates were septic. In all infected neonates, suPAR levels were repeated at 24 hours, 48 hours, 3-5 days, and 7-10 days following admission. RESULTS: Plasma suPAR levels were significantly increased in infected neonates upon admission, whereas they were highest in septic neonates, in comparison with controls (P < 0.001) and correlated positively with serum CRP levels (P = 0.001). At infection subsidence, suPAR concentrations decreased significantly in comparison with baseline (P < 0.001) but remained higher than in controls (P = 0.01). Receiver operating characteristic analysis resulted in significant areas under the curve for detecting either infected or septic neonates, but not for discriminating between bacterial and viral cause of infection. CONCLUSIONS: suPAR is a diagnostic biomarker of infection or sepsis in term neonates; however, it cannot discriminate bacterial from viral infections and also its utility for monitoring the response to treatment is questioned.

SARS-CoV-2 Seroepidemiology and Antibody Levels in Children during BA.5 Predominance Period.

This is a SARS-CoV-2 seroepidemiological study in a pediatric population (0-16 years) during the BA.5 Omicron predominance period in the Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies (Abs-N), representing natural infection during three periods of BA.5 predominance: 1 May 2022-31 August 2022 (period A), 1 September 2022-31 December 2022 (period B), and July 2023 (period C). Εpidemiological data were also collected. Additionally, in period C, Abs-N-seronegative samples were tested for SARS-CoV-2 spike antibodies (Abs-S). A total of 878 children were tested (males: 52.6%), with a median age (IQR) of 96 (36-156) months; the number of cases of seropositivity during the three periods were as follows: A: 292/417 (70%), B: 288/356 (80.9%), and C: 89/105 (84.8%), with p < 0.001. SARS-CoV-2 seropositivity increased from period A to C for children 0-1 year (p = 0.044), >1-4 years (p = 0.028), and >6-12 years (p = 0.003). Children > 6-12 years had the highest seropositivity rates in all periods (A: 77.3%, B: 91.4%, and C: 95.8%). A significant correlation of monthly median Abs-N titers with monthly seropositivity rates was detected (rs: 0.812, p = 0.008). During period C, 12/105 (11.4%) Abs-S-seropositive and Abs-N-seronegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The findings of this study indicate a high SARS-CoV-2 exposure rate of children during the BA.5 predominance period and suggest that in future seroepidemiological studies, both antibodies should be tested in Abs-N-seronegative populations.

Calprotectin: a protein related to cardiovascular risk in adult patients with obstructive sleep apnea.

INTRODUCTION: Increased levels of inflammatory mediators, such as hs-CRP, have been detected in patients with obstructive sleep apnea (OSA) and used as cardiovascular risk and disease outcome predictors. Calprotectin is an inflammatory marker regulating atherogenic processes not investigated in adult OSA patients. The aim of the present study as primary objective was to examine the role of calprotectin as an inflammatory molecule, acting through a distinct pathway to the atherogenic process in adult OSA patients and its associations with hs-CRP and the lipidemic profile of the patients. As a secondary objective was the evaluation of the atherogenic markers post-CPAP treatment. MATERIALS AND METHODS: Seventy-four participants underwent full overnight polysomnography. Blood samples were collected for calprotectin, hs-CRP, total cholesterol, triglycerides, LDL, HDL and glucose levels. Thirty-two OSA patients were reexamined 6 months post-CPAP treatment. RESULTS: Out of 74 participants included in the study, 33 had moderate OSA, 27 had severe OSA and 14 were controls. Calprotectin and hs-CRP were significantly increased in patients with moderate and severe OSA compared to controls (p<0.0001). Calprotectin and hs-CRP levels were positively correlated with apnea-hypopnea index, BMI and total time of sleep with SaO(2)<90% and inversely correlated with SaO(2) minimum and mean values. Calprotectin and hs-CRP levels were significantly improved post-CPAP treatment (p<0.0001). DISCUSSION: Calprotectin may serve as a novel and reliable, biomarker of cardiovascular risk severity in OSA patients. The decrease of calprotectin levels post-CPAP treatment combined with hs-CRP amelioration could provide evidence for reduction of cardiovascular risk post CPAP treatment.

Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon?

BACKGROUND: In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children's metabolic profile compared with controls. The recently reported lipocalins retinol-binding protein 4 (RBP-4) and neutrophil gelatinase-associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP-4 and NGAL as well as visfatin in children born after IVF. SUBJECTS AND METHODS: A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 4-14 year, were studied cross-sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP-4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated. RESULTS: Children born after IVF had significantly higher RBP-4 (P = 0·009) and NGAL (P = 0·028) levels than controls. When divided by gender, RBP-4 remained higher in IVF girls (P = 0·002), whereas NGAL was higher in IVF boys (P = 0·021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se. CONCLUSIONS: In our study, IVF children had significantly higher RBP-4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile.

Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely.

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction.

Serum YKL-40 as a Potential Biomarker for Sepsis in Term Neonates-A Pilot Study.

Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal sepsis is not known. The study objectives included assessing the levels and diagnostic value of serum YKL-40 in term neonates with sepsis and comparing YKL-40 with other commonly used inflammatory biomarkers. In this pilot case-control study, 45 term neonates (30 septic and 15 non-septic, as controls), 4 to 28 days old, were prospectively studied. The International Pediatric Sepsis Consensus Conference criteria were applied to diagnose sepsis. During the acute phase (admission) and remission of sepsis, blood samples were collected from cases (while from controls they were only collected once) for routine laboratory tests, cultures, and the measurement of serum YKL-40 levels via Elisa. In the acute phase of sepsis, YKL-40 levels were significantly elevated in comparison with remission (p = 0.004) and controls (p = 0.003). YKL-40 levels did not differ significantly between patients in remission and controls (p = 0.431). Upon admission, YKL-40 levels correlated positively with white blood count, absolute neutrophil count, and CRP levels. Via ROC analysis, it was shown that YKL-40 levels upon admission were a significant indicator of sepsis (AUC = 0.771; 95% CI 0.632-0.911; p = 0.003). Serum YKL-40 might be considered as an adjuvant biomarker of sepsis in term neonates.

Severe hyperinsulinemia, decreased GLUT3 and GLUT4 expression, and increased retinol binding protein 4 in a patient with chronic graft-versus-host disease post bone marrow transplantation.

Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT, especially following cGvHD. In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of inflammation, adiponectin and RBP4, body composition analysis, and the kinetics of GLUT3 and GLUT4 in circulating monocytes were evaluated. Hyperinsulinemia, associated with partial lipodystrophy, elevated RBP4, low adiponectin levels, and decreased expression of GLUT3 and GLUT4 were detected. The defects disclosed in this particular patient possibly explain, at least in part, the mechanisms underlying insulin resistance in patients undergoing BMT. It is not clear whether insulin resistance was caused by the drugs, the process itself, or the residual damage to the muscles and/or adipose tissue.

Angiotensin blockade in diabetic patients decreases insulin resistance-associated low-grade inflammation.

BACKGROUND: Insulin-resistant states, such as metabolic syndrome and diabetes mellitus type 2 (DM2), have been associated with chronic low-grade systemic inflammation. Elevated levels of interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1) and C-reactive protein (hs-CRP), are found in patients with type 2 diabetes with and without complications. Angiotensin II (Ang II), a potent vasopressor, seems to regulate also the expression of the above inflammatory mediators acting as proinflammatory cytokine. In this study, we examined the effects of candesartan, an angiotensin receptror blocker, in the chronic low-grade inflammation observed in DM 2. MATERIALS AND METHODS: Seventeen patients with DM2 of <5years duration were recruited for the study. Patients received 4mg of candesartan, an angiotensin receptor blocker, for 6months. Blood levels of IL-6, MCP-1, hs-CRP and other inflammatory indices were measured before and at the end of candesartan administration. RESULTS: At the end of treatment with candesartan, IL-6 levels decreased significantly (P<0·05). Serum levels of MCP-1 and hs-CRP showed a trend for significant decrease with treatment (P<0·08 and P<0·09, respectively). Statistically significant correlations were found between hs-CRP and MCP-1 (r=0·623, P< 0·05), IL-6 and MCP-1 (r=0·703, P<0·05) and TRT and MCP-1 (r=0·752, P<0·05), before but not at the end of candesartan administration. CONCLUSIONS: Candesartan could decrease the low-grade inflammation of type 2 DM as shown by the decrease of inflammatory mediators. Thus, angiotensin receptor blockers could be useful for treating patients with DM2 not only for their antihypertensive capacity but also for their anti-inflammatory actions.

Cystatin C levels in patients with beta-thalassemia during deferasirox treatment.

Deferasirox (Exjade) is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload. This study was conducted to analyze changes in cystatin C concentration, an endogenous marker of glomerular filtration rate (GFR), in patients with thalassemia receiving daily deferasirox therapy over a period of at least 9 months. One hundred and fifty beta-thalassemia patients were treated with deferasirox at doses of 20-40 mg/kg/day for 9 consecutive months. Cystatin C concentrations were measured at regular intervals and GFR was calculated according to the cystatin C-based prediction equation. Plasma concentrations of NGAL protein and NT-proBNP were also monitored as indicators of renal function and LVEF, respectively. Serum ferritin concentration was also measured to assess iron overload. Throughout the 9 months of deferasirox treatment cystatin C concentration remained stable (p>0.850). The baseline cystatin C mean values were 0.97+/-0.27 mg/L and reached a maximum of 1.01+/-0.29 mg/L at 4 months of treatment. No correlation was found between cystatin C and NGAL concentrations (p>0.674). Cystatin C and NT-proBNP concentrations correlated positively with a binomial equation (p<0.004), as also did cystatin C and serum ferritin (p<0.001). These findings suggest that slight changes of cystatin C during deferasirox treatment may not reflect renal injury. However hemodynamic signals such as LVEF alterations and iron mobilization do appear to affect changes in cystatin C concentration.

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.

Effect of inflammation induced by prolonged exercise on circulating erythroid progenitors and markers of erythropoiesis.

BACKGROUND: Exercise in humans augments the mobilization of circulating hematopoietic progenitor cells (CD34(+)) from the bone marrow. We investigated the effect of inflammation on erythroid marrow activity by mobilization of erythroid progenitor cells (EPs) along with soluble markers of erythropoiesis. METHODS: Ten healthy athletes who participated in an ultradistance foot race participated in the study. Peripheral blood mononuclear cells were isolated, before (phase I), at the end (phase II), and at 48 h post-race (phase III). EPs were detected as burst colony forming units (BFU-e) and colonies were scored at day 14. Markers of inflammation (C-reactive protein, serum amyloid-A, interleukin-6, ferritin and S100B) and bone marrow activity (erythropoietin, soluble transferrin receptor and lipocalin-2) were assessed. RESULTS: An approximately three-fold decrease in BFU-e number was observed at phase II. sTfR concentrations were also decreased at phase II and remained decreased at phase III. However, EPO and lipocalin-2 concentrations reached a maximum value at phase II, with a tendency to decrease at phase III. CONCLUSIONS: These findings indicate that exercise-induced inflammation modulates bone marrow homeostasis leading to an increase in leukocyte turnover and a decrease in erythroid compartment. It appears that lipocalin-2 is the main factor that regulates the production and mobilization of EPs.