Diagnostic Value of Upar, IL-33, and ST2 Levels in Childhood Sepsis.

BACKGROUND: The aim of this study was to evaluate the diagnostic value of Upar, IL-33, and ST2 in comparison with C-reactive protein, TNF-α, and Interleukin-6 in childhood sepsis. METHODS: A total of 128 children were included and 20 of them were the control group. We used only data showing a high probability of sepsis with blood culture positive children, because of this reason 68 children were excluded. Blood was collected from children from first day of sepsis (1st value) and 48 - 72 hours later (2nd value). RESULTS: There were significant differences between control and sepsis (1st value) for IL-33 levels (1.1 ± 0.28 ng/ mL and 5.23 ± 1.80 ng/mL, p = 0.01), for sST2 levels (6.73 ± 5.3 ng/mL and 53.23 ± 28.30 ng/mL, p = 0.01), for sUpar levels (3.3 ± 1.7 ng/mL and 15.2 ± 6.3 ng/mL, p = 0.01), respectively. There were significant differences between sepsis (1st value) and sepsis (2nd value) for IL-33 levels, for sST2 levels, and for suPAR levels. CONCLUSIONS: In the light of these results, it may be suggested that Upar, IL-33, and ST2 can be used as an acute phase reactant like C-reactive protein, TNF-α, and Interleukin-6 in the diagnosis of childhood sepsis.

Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury.

BACKGROUND: Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury. METHODS: Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters. RESULTS: SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3. CONCLUSIONS: We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.

Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development. METHODS: A total of 38 babies were studied prospectively on delivery to the neonatal intensive care unit. Serum levels of IL-33, sST2, and suPAR were measured using enzyme-linked immunosorbent assay. Serum samples were collected from umbilical cord (at the time of delivery, termed CB) and peripheral blood (on day 14, termed PB). RESULTS: Levels of suPAR (PB-suPAR) and sST2 (PB-sST2) in the peripheral blood of the BPD group were significantly higher than the corresponding levels in the non-BPD group (P < 0.001, P = 0.028, respectively. There was a statistically significant correlation between PB-suPAR levels and the severity of BPD (P < 0.001)) when the suPAR results were analyzed using the receiver operating characteristic curve. CONCLUSION: PB-suPAR and PB-sST2 levels are sensitive and specific independent predictive biomarkers in preterm babies with BPD.

Protective effects of melatonin therapy in model for neonatal hyperoxic lung injury.

CONTEXT: Bronchopulmonary dysplasia (BPD) is a common outcome of premature birth. Currently, no effective preventive therapy is available for BPD, but the major role of O2 toxicity in the development of BPD has gained attention, particularly for developing new antioxidants for prevention. The major protective mechanism of melatonin (MT) includes free-radical scavenging activity and activation of the cyclooxygenase-prostoglandin enzyme system. OBJECTIVE: The aim of this study was to evaluate the effects of MT on cytoprotection and healing in a model of hyperoxic lung injury in newborn rats. METHODS: This is a case-control study design. SETTING: The study occurred at the Gulhane Military Medical Academy in Ankara, Turkey. INTERVENTION: A total of 60 newborn pups from dated, Sprague-Dawley, pregnant rats were divided equally into 3 groups as follows: (1) control group, (2) hyperoxia-exposed group, and (3) hyperoxia-exposed plus MT-treated group (MT group). Hyperoxia was performed by placing these pups in an oxygen chamber for 14 d during which oxygen was continuously delivered. OUTCOME MEASURES: At the end of the 14 d, lung specimens were collected and evaluation of the lamellar-body count and determination of histopathological scores were performed. Also, the activities of superoxide dysmutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were assessed. RESULTS: The histopathological scores of the MT group were significantly lower than those of the hyperoxia-exposed group. The mean lamellar-protein and radial-alveolar counts in the MT group were found to be significantly higher than those of the hyperoxia-exposed group. Also, SOD and GSH-Px levels were significantly higher and MDA levels were significantly lower in the MT group compared with the hyperoxia-exposed group. CONCLUSION: MT therapy was found to have a protective effect in a model for hyperoxic lung injury in neonatal rats. Therefore, the research team suggests that MT therapy may be used for prevention of BPD in preterm infants after confirmation of this data by future clinical studies.

High serum 25-hydroxyvitamin D levels are associated with pediatric sepsis.

Despite major advances in intensive care, sepsis continues to be a major cause of morbidity and mortality. Vitamin D is involved in various physiologic functions, including cellular responses during infection and inflammation. The aim of this study was to evaluate diagnostic value of 25-hydroxyvitamin D in childhood sepsis because it can be fatal if diagnosis delayed. The study included 40 children with sepsis and 20 children without sepsis (control group). We included only the patients with high probable sepsis, judged by clinical and laboratory findings, including positive blood culture. Blood samples were collected from patients with sepsis before treatment (pre-treatment group) and 48-72 hours later (post-treatment group). Treatment varied from ampicillin-sulbactam to cephalosporin. Blood samples were collected from control group once on admission. Serum 25-hydroxyvitamin D levels were significantly higher in sepsis (pre-treatment group) than control group (74 ± 8 ng/ml vs. 28 ± 12 ng/ml, p = 0.01) and the serum 25-hydroxyvitamin D levels were decreased to 44 ± 5 ng/ml (p = 0.01) after treatment. Moreover, we found significant positive correlation between 25-hydroxyvitamin D and each of well-know sepsis markers, C-reactive protein, tumor necrosis factor-α and interleukin-6. A cut-off point of 20 ng/mL for serum 25-hydroxyvitamin D showed 84% sensitivity and 76% specificity for sepsis diagnosis. This is the first study evaluating the diagnostic role of vitamin D in pediatric sepsis, thereby suggesting that serum 25-hydroxyvitamin D level can be used as a diagnostic marker for sepsis with high sensitivity and specificity.

Cytidine 5'-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. METHODS: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O2 and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. RESULTS: Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after CDP-choline administration. CONCLUSION: These data show that CDP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.

CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. RESULTS: Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC lesions. CONCLUSIONS: Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC.

Malignant epignathus including a nephroblastoma component and successful management.

A male infant was born to a 24-year-old mother (gravida 1 para 1) by cesarean delivery at 33 1/7 weeks of gestation. The physical examination revealed a large mass protruding from the baby's mouth, which appeared to be attached to the palate. Tracheostomy was performed immediately in the delivery room. A partial surgical excision was performed on the second postnatal day, removing most of the teratoma (epignathus), which was attached to the back of the pharynx and protruding from the baby's mouth measuring 13×11×9 cm and weighing 545 g. The final pathological diagnosis was "malignant epignathus with nephroblastoma component." According to our knowledge, this is the first case that have malignant epignathus including nephroblastoma component in the literature.

Low 25-hydroxyvitamin D level and adiponectin is associated with insulin sensitivity in large gestational age infants.

OBJECTIVE: To investigate the relationship between adipokines (visfatin, adiponectin) and 25-hydroxyvitamin D (25(OH)D), and markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (25 LGA born to diabetic mothers and 15 LGA born to non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. RESULTS: FGIR, QUICK-I, adiponectin and 25(OH)D levels were significantly lower in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. HOMA-IR, fasting insulin, visfatin and parathormone (PTH) levels were significantly higher in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. CONCLUSION: Based on the findings of this study, visfatin, adiponectin and 25(OH)D levels can be used as specific markers for insulin sensitivity and may help advance new therapies for glucose intolerance spectrum.

Increased fecal calprotectin in preterm infants with necrotizing enterocolitis.

BACKGROUND: Necrotizing entrocolitis (NEC) remains a potentially fatal disease in premature infants despite the recent advances in neonatal care. It is a disease with a multifactorial etiology leading to the one common final pathway of necrosis and inflammmation of the neonatal intestine. METHODS: Calprotectin is a calcium and zinc-binding protein in human neutrophils. Its concentration rises in various organic bowel diseases in adults and is resistant to degradation and has been proposed as a useful, simple, and rapid diagnostic method of inflammatory bowel disease that shows gastrointestinal inflammation in children and adults. RESULTS: We found that infants with necrotizing enterocolitis had increased fecal calprotectin concentrations, and there was a correlation between calprotectin concentrations and severity of NEC. CONCLUSIONS: We concluded that fecal calprotectin is a useful marker for diagnosis and severity of NEC in preterm infants.

Comparing beneficial effects of inhaled nitric oxide to L-arginine in necrotizing enterocolitis model in neonatal rats.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal condition of neonatal infants. The pathophysiology of NEC remains poorly understood. We tried to evaluate the effectiveness of inhaled NO compared to L-arginine usage in necrotizing enterocolitis model in rats. MATERIAL-METHODS: 46 newborn pups from 4 time-mated Sprague-Dawley pregnant rats were divided equally into 4 groups as follows: NEC (subjected to NEC), NEC + L-arginine, NEC + inhaled NO and control. RESULTS: SOD, GSH-Px and NOx levels were significantly higher and MDA levels were significantly lower in NEC + inhaled NO group compared to NEC + L-arginine group. There was significantly lower intestinal injury and apoptosis index scoring in NEC + inhaled NO group compared to NEC + L-arginine group. CONCLUSION: We think that inhaled NO can be used as a novel therapeutic agent like L-arginine in NEC, like using in pulmonary hypertention in newborns but much more studies are needed.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance.

OBJECTIVE: To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. RESULTS: HOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. CONCLUSION: Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.

Insulin-like growth factor-1 levels in twins and its correlation with discordance.

This study aims to determine whether fetal growth is related to insulin-like growth factor-1 in dichorionic and monochorionic twins and also aims to investigate the correlation of insulin-like growth factor-1 to birthweight discordance in twins. We studied 100 women with twin pregnancies. The correlation tests of 36 discordant twins (15 monochorionic, 21 dichorionic) showed correlation between insulin-like growth factor-1 difference and birthweight discordance (insulin-like growth factor-1 vs. birthweight of first twin, r = +0.915, at 0.01 level, IGF-1 vs birthweight of second twin r = +0.790, at 0.01 level). In 49 monochorionic twins, independent of discordance, there was a correlation between birthweight discordance and insulin-like growth factor-1 difference (r = .538, at the 0.01 level). This correlation was not significant in dichorionic twins, r = .144, p = .01. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in IGF-1, depending upon the genetic similarity.

Evaluation of adipocytokines in obese children with insulin resistance.

Obesity and overweight are among the most serious health problems in western societies and an increasing problem in developing countries. Recent studies indicate an important role of adipose tissue hormones, or "adipokines", in obesity-associated complications. To investigate the relation of two circulating adipokines (visfatin, adiponectin) with markers of insulin sensitivity and obesity in children, 40 obese children and 40 control children were recruited. Homeostasis model assessment for insulin resistance (HOMA-IR) and visfatin levels (4.99 +/- 2.08 vs. 1.47 vs. 0.7, p < 0.001; 31.3 +/- 11.1 vs. 18.5 +/- 10.7, p < 0.001, respectively) were significantly elevated and adiponectin levels (2.01 +/- 1.02 vs. 12.5 +/- 6.2, p < 0.001) were significantly lower in the obese group. Comparisons of the clinical and metabolic characteristics between insulin-resistant and noninsulin-resistant groups in obese children are summarized. The insulin-resistant group had higher visfatin levels (36 +/- 9.7 vs. 22.9 +/- 7.6, p < 0.001) and lower adiponectin levels (1.7 +/- 1.05 vs. 2.5 +/- 0.77, p: 0.016). Visfatin was correlated positively and adiponectin was correlated negatively with body mass index standard deviation score (BMI-SDS) and HOMA-IR. The role of various adipokines as connectors between obesity and diabetes mellitus has been better elucidated in recent years. Based on the findings of this study, visfatin and adiponectin levels can be used as specific markers for insulin sensitivity.

Elevated plasma levels of apelin in children with type 1 diabetes mellitus.

BACKGROUND: Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. OBJECTIVE: To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. METHODS: Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. RESULTS: Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. CONCLUSIONS: Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.

The effect of the pre-pregnancy weight of the mother and the gestational weight gain on the bilirubin level of term newborn.

OBJECTIVE: Jaundice is a problem in newborns. There are many maternal and infant-related factors affecting neonatal jaundice. The maternal pre-pregnancy weight, maternal body mass index (BMI) and gestational weight gain may have an effect on the newborn bilirubin levels. We research the effect of the maternal pre-pregnancy weight and gestational weight gain on the bilirubin levels of the newborn infants in the first 2 weeks prospectively. METHODS: Term and healthy infants who were born between 38 and 42 weeks in our clinic were included in the study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into three groups according to their mothers' advised amount of gestational weight gain. Total serum bilirubin (TSB) values of the newborns were measured in the 2nd, 5th and 15th postnatal days. RESULTS: In our study, the 5th and 15th day capillary bilirubin level of the babies with mothers who gained more weight than the advised amount during pregnancy were found statistically significant higher compared to the other two groups (p < 0.05). Similarly, the hematocrit level of the babies with mothers who gained more weight than the advised amount were found statistically significant higher compared to the other two groups (p < 0.05). CONCLUSIONS: We conclude that the babies with mothers who gained more weight than the advised amount were under risk for newborn jaundice. Therefore, these babies should be monitored more closely for neonatal jaundice and prolonged jaundice.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.