Mehmet Saldir

Endocan and Soluble Triggering Receptor Expressed on Myeloid Cells-1 as Novel Markers for Neonatal Sepsis

BACKGROUND Neonatal sepsis is an important cause of neonatal morbidity and mortality in the neonatal intensive care unit. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) has been evaluated in sepsis and septic shock, and it was found to be valuable in distinguishing septic cases from nonseptic cases. Endocan is constitutively expressed by endothelial cells, and high levels of endocan may be of relevance for the promotion of systemic inflammation. The aim of this study was to investigate whether the levels of sTREM-1 and endocan were increased in late-onset neonatal sepsis. METHODS Patients were classified into septic and nonseptic groups. Blood was collected from a peripheral vein of all septic newborns and healthy newborns at the time of initial laboratory evaluation before any treatment, and within 48-72 hours after initiation of treatment. Serum sTREM-1 and endocan measurements were performed when the study was finished. RESULTS The study population comprised of 50 neonates: 20 nonseptic neonates and 30 septic neonates. The groups were similar with regards to baseline characteristics. The initial measurements of interleukin-6 (IL-6), sTREM-1, endocan, and immature/total neutrophil ratio (I/T ratio) were significantly higher in septic neonates in comparison with nonseptic neonates. Receiver operating characteristic (ROC) curve analyses revealed that IL-6, sTREM-1, endocan, and I/T ratio resulted in significant areas under the curve (AUC) with respect to early identification of septic neonates. Soluble TREM-1 and IL-6 performed best to distinguish septic neonates from nonseptic neonates. Univariate logistic regression analysis showed that increased IL-6 and sTREM-1 were strong predictors of neonatal late-onset sepsis. CONCLUSION Serum sTREM-1, IL-6, endocan levels, and I/T ratio increased in septic neonates. However, the diagnostic accuracy of circulating sTREM-1 seemed to be better than endocan and I/T ratio, but lower than IL-6.

Neurodevelopmental status of preterm newborns at infancy, born at a tertiary care center in Turkey.

Our objective was to determine the incidence of early neonatal problems and the neurodevelopmental status and probable risk factors associated with neurodevelopmental abnormality in preterm infants of < or = 32 weeks of gestation. Preterm newborns of < or = 32 weeks of gestation followed at the neonatal intensive care unit of the Department of Pediatrics of Gülhane Military Medical Academy, Ankara, Turkey, were evaluated with a complete neurological examination and the Bayley Scales of Infant Development at a mean age of 25.85 + or - 11.79 months (range, 10 to 42 months). Multivariate logistic regression analyses were performed to determine the probable risk factors associated with neurodevelopmental abnormalities. Regarding the results of the neurological examination in a total of 169 preterms included in the study, 28 (16.6%) and 14 (8.3%) patients were determined to have mild neurological dysfunction or cerebral palsy, respectively. The rate of psychomotor abnormality according to a low Bayley Psychomotor Development Index (PDI) score was 24.8%, and the rate of mental/cognitive abnormality on the basis of a low Bayley Mental Development Index (MDI) score was 25.4%. In the subgroup of infants with < or = 29 weeks of gestational age (n = 55); 22 (40%) patients had an abnormal neurological examination, and 24 (43.6%) and 23 (41.8%) patients had low Bayley PDI and MDI scores, respectively. In the study group, logistic regression analysis revealed the significant predictors of an abnormal neurological examination to be the duration of mechanical ventilation (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.062 to 1.208) and necrotizing enterocolitis (OR, 6.697; 95% CI, 1.776 to 25.252). One of the major conclusions of the present study is the risk of neurodevelopmental sequelae in one of every four preterm infants with <32 weeks of gestation and the need for follow-up in this group. Measures in neonatal care and treatment, such as the use of less traumatic modes of mechanical ventilation with as short duration as possible as well as increasing perinatal/antenatal care, should be taken to overcome these risk factors.

The effect of melatonin on procarbazine induced testicular toxicity on rats

Abstract Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects.

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.

An Analysis of Neonatal Risk Factors Associated With the Development of Ophthalmologic Problems at Infancy and Early Childhood: A Study of Premature Infants Born at or Before 32 Weeks of Gestation

BACKGROUND To determine the frequency of ophthalmologic problems and the risk factors that affect the occurrence of these problems in premature newborns with a gestational age of 32 weeks or less. METHODS Premature newborns observed at a neonatal intensive care unit between January 2002 and March 2006 were included. A control visit including an ophthalmologic examination was performed at 10 months of age or later. Primary ocular morbidities were studied, and the association between these parameters and prenatal, perinatal, and neonatal characteristics were evaluated. RESULTS A total of 169 premature newborns were included in the study, and they were examined at a mean age of 25.85 ± 11.79 months (range: 10 to 42 months). There was complete vision loss (blindness) in 1 (0.6%) case, strabismus in 15 (8.9%) cases, and refractive errors in 10 (5.9%) cases. Twenty (77%) cases with any abnormality and 50 (35%) cases with a normal examination at follow-up had a history of retinopathy of prematurity (ROP) at any stage during the neonatal period (P = .001). Short gestational age (P = .018), low birth weight (P = .002), and the presence of ROP requiring retinal surgery during the neonatal period (P = .007) were determined to be significant risk factors for the development of vision loss, strabismus, and refractive errors. CONCLUSION Neonates with a gestational age of 32 weeks or less, especially those younger than 30 weeks, should not only be screened for ROP in the neonatal period, but should also have regular follow-up examinations to check for the development of other ophthalmologic problems during infancy and early childhood.

Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis

Abstract Objective: Neonatal sepsis remains a major cause of morbidity and mortality in newborns. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in inflammatory states. However, it is unclear how chemokines respond to late-onset neonatal sepsis. Methods: Patients were classified into the groups of septic and non-septic ones. Samples of venous blood were obtained from all septic and non-septic newborns at the beginning and within 48–72 h after initiation of treatment. Serum levels of CXCR4 and CXCL12 were measured. Results: Concentrations of IL-6, CXCR4 and CXCL12 at the time of diagnosis were significantly higher in the septic neonates compared with the non-septic ones. Additionally, there were statistically significant differences in septic neonates between the first and the second levels of IL-6, CXCR4, CXCL12 and I/T ratio. ROC curve analyses revealed that IL-6, CXCR4, CXCL12 and I/T ratio resulted in significant AUC with respect to early identification of septic neonates. Univariate logistic regression analysis showed that increased IL-6, CXCR4 and CXCL12 were strong predictors of neonatal LOS. Conclusions: Serum CXCR4 and CXCL12 levels increase in septic neonates and that both chemokines decrease within 48–72 h of treatment. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.

Metabolic and Histopathological Effects of Fructose Intake During Pregestation, Gestation and Lactation in Rats and their Offspring

Objective: Studies have demonstrated a significant relationship between maternal fructose intake and metabolic outcome in their offspring. However, there is a paucity of data about the long-term effects of fructose intake on the offspring of fructose-fed dams. Therefore, we planned a study to evaluate the long-term effects of fructose intake on the offspring of dam rats fed a high-fructose diet. Methods: Sixteen virgin female Sprague-Dawley rats were divided into two groups. Group 1 received a regular diet and Group 2 a high-fructose diet. Both groups received their experimental diets for 8 weeks before conception. They were mated and continued to feed with their experimental diet during mating and during their pregnancy and lactation periods. After weaning, the offspring from each group were divided into two groups. Group 1A received a regular diet, Group 1B - a fructose diet, Group 2A - a regular diet and Group 2B received a fructose diet. After weaning, the offspring were anesthetized and blood samples were collected for biochemical analysis. Liver, kidney and retroperitoneal adipose tissue were harvested for histopathological examination. Primary antibodies against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined as early inflammation markers. Results: After weaning, while daily water consumption was found to be significantly higher in Groups 2B and 1B (p<0.01), daily laboratory chow consumption was significantly lower in Groups 1A and 2A (p<0.01). Body weight was significantly higher in Groups 1B and 2B (p<0.01). Serum glucose, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were found to be increased and high-density lipoprotein cholesterol levels decreased in Group 2B (p<0.05). The intensities of iNOS staining in the retroperitoneal adipose tissue, COX-2 staining in the liver and both iNOS and COX-2 staining in the kidney were higher in Group 2B (p<0.05). Conclusion: Based on our findings, we believe that the offspring of dams which received a high fructose intake during their pregestation, gestation and lactation periods are at risk of developing metabolic syndrome in their later life only if they continue to receive a high intake of fructose. We therefore propose that the risk of developing metabolic syndrome can probably be reduced by modifying the diet of the offspring after weaning.

Measures of pituitary gland and stalk: from neonate to adolescence.

Abstract Objective: The aim of this study is to provide normative data about pituitary diameters in a pediatric population. Pituitary imaging is important for the evaluation of the hypothalamo-pituitary axis defect. However, data about normal pituitary gland diameters and stalk are limited, especially in children. Structure and the measurements of pituitary gland and pituitary stalk may change due to infection, inflammation, or neoplasia. Methods: Among 14,854 cranial/pituitary gland magnetic resonance imaging scans performed from 2011 to 2013, 2755 images of Turkish children aged between 0 and 18 were acquired. After exclusions, 517 images were left. Four radiologists were educated by an experienced pediatric radiologist for the measurement and assessment of the pituitary gland and pituitary stalk. Twenty cases were measured by all radiologists for a pilot study and there was no interobserver variability. Results: There were 10–22 children in each age group. The maximum median height of the pituitary gland was 8.48±1.08 and 6.19±0.88 mm for girls and boys, respectively. Volumes were also correlated with gender similar to height. Minimum median height was 3.91±0.75 mm for girls and 3.81±0.68 mm for boys. The maximum and minimum pituitary stalk basilar artery ratios for girls were 0.73±0.12 and 0.59±0.10 mm. The ratios for boys were 0.70±0.12 and 0.56±0.11 mm. Conclusion: Our study demonstrated the pituitary gland and stalk size data of children in various age groups from newborn to adolescent. It is thought that these data can be applied in clinical practice. Future prospective follow-up studies with larger samples, which correlate the structural findings with the clinical and laboratory results are awaited.

First report on the nationwide incidence and prevalence of Type 1 diabetes among children in Turkey.

To report, for the first time, the incidence and prevalence of childhood Type 1 diabetes in Turkey using a nationwide registry.

Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.

In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mothers milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mothers milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mothers milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mothers milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.