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.

Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model.

Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL1ß), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-α level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1ß levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation.

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 mother's 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 mother's 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 mother's 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 mother's 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.

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.

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.

Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis.

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.

Effects of maternal smoking on fetal organs.

BACKGROUND: Unfavorable effects of in-utero smoke exposure have been shown in several studies. OBJECTIVES: In this experimental study, the authors aimed at showing detrimental effects of cigarette smoke on fetal tissues by assessing apoptosis that is detected by performing TUNEL staining. MATERIAL AND METHODS: Designed groups were smoke exposed rats before and during pregnancy and control groups. Rat offsprings were sacrificed when they were 12 days old. RESULTS: Lung, kidney, adrenal and gonad tissues were harvested for histopathologic analysis and assessed by TUNEL (Terminal dUTP Nick End Labeling) staining. CONCLUSIONS: Smoke exposure caused increased apoptotic activity in lung parenchyma of study groups.