Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome.

PURPOSE: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. METHODS: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. RESULTS: The BAL fluid TNF-α, IL-1ß, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION: Meconium-induced inflammatory cytokine production is affected by the body temperature control.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome.

BACKGROUND: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). PURPOSE OF THE STUDY: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. MATERIALS AND METHODS: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. RESULTS: Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1ß, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). CONCLUSION: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.

The effects of fibroblast growth factor-2 and pluripotent astrocytic stem cells on cognitive function in a rat model of neonatal hypoxic-ischemic brain injury.

OBJECTIVE: This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI). METHODS: The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months. RESULTS: PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p < 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms. CONCLUSIONS: Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance.

Mesenchymal stem cell treatment in hyperoxia-induced lung injury in newborn rats.

BACKGROUND: The aim of this study was to evaluate the effectiveness of tracheally delivered mesenchymal stem cells (MSC) on lung pathology in a hyperoxia-induced lung injury (HILI) model in neonatal rats. METHODS: For the HILI model, rat pups were exposed to 85-95% oxygen during the first 10 days of life. Rats were divided into six groups: room-air normoxia (n = 11); room air, sham (n = 11); hyperoxia exposed with normal saline as placebo (n = 9); hyperoxia exposed with culture medium of MSC (n = 10); hyperoxia exposed with medium remaining after harvesting of MSC (n = 8); and hyperoxia exposed with MSC (n = 17). Pathologic changes, number and diameter of alveoli, α-smooth muscle actin (α-SMA) expression and localization of MSC in the lungs were assessed. RESULTS: Number of alveoli increased and alveolar diameter decreased in the mesenchymal stem cell group so that there were no differences when compared with the normoxia group (P = 0.126 and P = 0.715, respectively). Expression of α-SMA decreased significantly in the mesenchymal stem cell group compared with the placebo group (P < 0001). Green fluorescent protein-positive cells were found in lung tissue from all rats given MSC. Some green fluorescent protein-positive MSC also expressed surfactant protein-C. CONCLUSION: Mesenchymal stem cells became localized in damaged lung tissue, and recovery approximated the room air control.

Comparison of selective head cooling versus whole-body cooling.

BACKGROUND: This study compared selective head cooling (SHC) and whole-body cooling (WBC) in newborns with hypoxic-ischemic encephalopathy (HIE). METHODS: We conducted a prospective randomized small-scale pilot study in newborns with HIE, born after >35 weeks of gestation. The patients were randomly assigned to receive SHC or WBC. RESULTS: The SHC group consisted of 17 patients, and the WBC group, 12 patients. There was no significant difference in adverse effects related to cooling therapy between the two groups. During the 12 month study period, seven patients in the SHC group and four in the WBC group died, but the difference was not significant (P = 0.667). Among the patients alive at 12 months after treatment, six in the SHC group and four in the WBC group had severe disabilities; the difference was not significant (P = 0.671). When the composite outcome of death or severe disability was evaluated, the difference between the SHC group (77%, n = 13) and the WBC group (67%, n = 8) was not significant (P = 0.562). Moreover, the number of survivors without disability at 12 months after treatment did not differ significantly between the SHC group (n = 3) and the WBC group (n = 4; P = 0.614). CONCLUSIONS: There were no significant differences in adverse effects, 12 month neuromotor development, or mortality rate between SHC and WBC in newborns with HIE, born after >35 weeks of gestation.

The effects of selective head cooling versus whole-body cooling on some neural and inflammatory biomarkers: a randomized controlled pilot study.

BACKGROUND: Therapeutic hypothermia (TH) has become standard care in newborns with moderate to severe hypoxic ischemic encephalopathy (HIE), and the 2 most commonly used methods are selective head cooling (SHC) and whole body cooling (WBC). This study aimed to determine if the effects of the 2 methods on some neural and inflammatory biomarkers differ. MATERIALS AND METHODS: This prospective randomized pilot study included newborns delivered after >36 weeks of gestation. SHC or WBC was administered randomly to newborns with moderate to severe HIE that were prescribed TH. The serum interleukin (IL)-1ß, IL-6, neuron-specific enolase (NSE), brain-specific creatine kinase (CK-BB), tumor necrosis factor-alpha (TNF-α), and protein S100 levels, the urine S100B level, and the urine lactate/creatinine (L/C) ratio were evaluated 6 and 72 h after birth. The Bayley Scales of Infant and Toddler Development-III was administered at month 12 for assessment of neurodevelopmental findings. RESULTS: The SHC group included 14 newborns, the WBC group included 10, the mild HIE group included 7, and the control group included 9. All the biomarker levels in the SHC and WBC groups at 6 and 72 h were similar, and all the changes in the biomarker levels between 6 and 72 h were similar in both groups. The serum IL-6 and protein S100 levels at 6 h in the SHC and WBC groups were significantly higher than in the control group. The urine L/C ratio at 6 h in the SHC and WBC groups was significantly higher than in the mild HIE and control groups. The IL-6 level and L/C ratio at 6 and 72 h in the patients that had died or had disability at month 12 were significantly higher than in the patients without disability at month 12. CONCLUSION: The effects of SHC and WBC on the biomarkers evaluated did not differ. The urine L/C ratio might be useful for differentiating newborns with moderate and severe HIE from those with mild HIE. Furthermore, the serum IL-6 level and the L/C ratio might be useful for predicting disability and mortality in newborns with HIE.

Accessory Nostril: A Rare Congenital Nasal Anomaly.

Accessory nostril is a very rare congenital anomaly with an unknown etiology also known as supernumerary nostril. A few accessory nostrils have been reported up to the present time, and extremely rare cases located on columella. A newborn infant with respiratory distress was referred to our hospital. The authors observed that accessory nasal nostril is not related to normal nasal cavity on the median line of columella. In this article, the authors reported accessory nostril case in newborn and review the literature.

Comparison of selective head cooling therapy and whole body cooling therapy in newborns with hypoxic ischemic encephalopathy: short term results.

AIM: In this study, it was aimed to investigate which method was superior by applying selective head cooling or whole body cooling therapy in newborns diagnosed with moderate or severe hypoxic ischemic encephalopathy. MATERIALS AND METHOD: Newborns above the 35th gestational age diagnosed with moderate or severe hypoxic ischemic encephalopathy were included in the study and selective head cooling or whole body cooling therapy was performed randomly. The newborns who were treated by both methods were compared in terms of adverse effects in the early stage and in terms of short-term results. Ethics committee approval was obtained for the study (06.01.2010/35). RESULTS: Fifty three babies diagnosed with hypoxic ischemic encephalopathy were studied. Selective head cooling was applied to 17 babies and whole body cooling was applied to 12 babies. There was no significant difference in terms of adverse effects related to cooling therapy between the two groups. When the short-term results were examined, it was found that the hospitalization time was 34 (7-65) days in the selective head cooling group and 18 (7-57) days in the whole body cooling group and there was no significant difference between the two groups (p=0.097). Four patients in the selective head cooling group and two patients in the whole body cooling group were discharged with tracheostomy because of the need for prolonged mechanical ventilation and there was no difference between the groups in terms of discharge with tracheostomy (p=0.528). Five patients in the selective head cooling group and three patients in the whole body cooling group were discharged with a gastrostomy tube because they could not be fed orally and there was no difference between the groups in terms of discharge with a gastrostomy tube (p=0.586). One patient who was applied selective head cooling and one patient who was applied whole body cooling died during hospitalization and there was no difference between the groups in terms of mortality (p=0.665). CONCLUSIONS: There is no difference between the methods of selective head cooling and whole body cooling in terms of adverse effects and short-term results.

A case of thanatophoric dysplasia type 2: a novel mutation.

Thanatophoric dysplasia (TD) is a lethal form of skeletal dysplasia with short-limb dwarfism. Two types distinguished with their radiological characteristics have been defined clinically. The femur is curved in type 1, while it is straight in type 2. TD is known to be due to a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. We report a male patient who showed clinical findings congruent with TD type 2 and a new mutation in the FGFR3 gene, a finding which has not been reported previously.

Effects of a tumor necrosis factor-alpha inhibitor (etanercept) on the sciatic nerve in a hypoxic ischemia-induced neonatal rat model.

BACKGROUND: Neonatal hypoxic-ischemic (HI) injury has been considered to have acute and long term deleterious effects on many tissues, including the peripheral nerve. OBJECTIVES: In this study, the effects of a tumor necrosis factor-alpha (TNF-a) inhibitor (etanercept) on peripheral nerve damage and the ultrastructure of the sciatic nerve and gastrocnemius muscle in rats exposed to HI during the neonatal period were examined. MATERIAL AND METHODS: In this study, 45 seven-day-old rats were used and they were divided into three groups. The right carotid arteries of the rats in the saline and etanercept groups were ligated and put in a hypoxia chamber containing 8% oxygen for two hours. Just after hypoxia, the etanercept group was given 10 mg/kg etanercept, but the saline group had only saline intraperitoneally. The sham group rats' carotid arteries were not ligated or put in hypoxia. The amplitude, area and latency of sciatic nerve compound motor action potential (CMAP), which mainly reflects axonopathy and myelinopathy, were measured using standard techniques in the seventeenth week following the HI. Sciatic nerve and gastrocnemius muscle were evaluated with a transmission electron microscope, and grading for myelin sheath damage was done to all groups. RESULTS: Neuropathy was seen in rats after HI. While treatment with etanercept showed a protective effect for the axons of sciatic nerve, demyelination could not be recovered with etanercept. CONCLUSIONS: This study is the first in literature to show a partial interruption of the signal through the peripheral nerve fibers caused by axonal and myelin dysfunction continuation in rats exposed to HI after birth, in the 17th week.

The effects of pentoxifylline on lung inflammation in a rat model of meconium aspiration syndrome.

To examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

The effect of tumor necrosis factor-α inhibitor soon after hypoxia-ischemia on heart in neonatal rats.

AIMS: Perinatal hypoxic-ischemic insult has acute and long term deleterious effects on many organs including heart. Although tumor necrosis factor alpha (TNF-α) has been reported to increase soon after hypoxia, the inhibition of this mediator has not been documented. The aim of this study was to investigate the effects of a TNF-α inhibitor (etanercept) on contractility and ultrastructure of rat heart muscles exposed to hypoxia-ischemia during neonatal period. MAIN METHODS: Forty-five seven-day old rats divided into three groups were included in this study. The right carotid arteries of Saline and Etanercept groups of rats were ligated and kept in a hypoxia chamber containing 8% oxygen for 2h. Immediately after hypoxia, while Etanercept group was administered 10mg/kg etanercept, Saline group had only saline intraperitoneally. The carotid arteries of rats in Sham group were located without ligation and hypoxia. Mechanical activity of heart was recorded and tissue samples were examined by electron microscopy in the sixteenth week following the hypoxia-ischemia. KEY FINDINGS: While atrial contractile force in Etanercept group was similar to Sham group, there was significant decrease in Saline group (p<0.001). However, there was only non-significant decrease in ventricular contractility of Saline group comparing to Sham group (p>0.05). After hypoxia-ischemia, ultrastructural degenerative changes and mitochondrial damage in atriums of Etanercept group were significantly less severe than Saline group. SIGNIFICANCE: This study demonstrated that neonatal hypoxia-ischemia caused long term cardiac dysfunction and ultrastructural degenerative changes in the heart of rats. TNF-α inhibitor administration soon after hypoxia-ischemia may have heart protective effect.

Peer training increases the level of knowledge on sexual and reproductive health in adolescents.

To reach 'youth' and equip them with accurate information on sexual and reproductive health (SRH) is a very important issue. Forty one volunteer students from Mersin University School of Medicine were trained as peer trainers on SRH in Mersin, Turkey. Every peer trainer then trained 100 peers aged between 15 and 20 years about SRH. A total of 3941 students participated and answered a questionnaire consisting of 20 questions about SRH before and after the training sessions. The mean score before the training session was 13.6 ± 3.2 and after the training session was 17.0 ± 2.8. The posttraining test results were found to be significantly higher (p < 0.001). Having previous SRH information from any kind of source also was found to be effective on pretraining test results positively (p = 0.002). As adolescence is the most vulnerable period to sexual health problems, increasing the awareness of sexual health is very important.

A girl with spastic tetraparesis associated with biotinidase deficiency.

Biotinidase deficiency is a disorder of biotin metabolism that manifests with cutaneous, ophthalmological and neurologyical symptoms in childhood. Spinal cord involvement has rarely been reported and all of the reported cases are spastic paraparesis. A 3 year-old girl with biotinidase deficiency was admitted to our clinic with hyperventilation, hair loss and spastic tetraparesis. To our knowledge, our case is the first reported tetraparesis associated with biotinidase deficiency. She was treated with oral biotin and benefited significantly from this therapy.

Antioxidant capacity of breast milk of mothers who delivered prematurely is higher than that of mothers who delivered at term.

BACKGROUND: The total antioxidant capacity of plasma of preterm infants has been suggested to be lower than that of term infants. The objective of this study was to compare the total antioxidant capacity of the breast milk of mothers who delivered prematurely with that of mothers who delivered at term. MATERIALS AND METHODS: A total of 71 breast milk samples were collected, 41 from mothers who delivered preterm (27 to 37 weeks) and 30 from mothers who delivered at term (38 to 42 weeks). RESULTS: The mean total antioxidant capacity of the breast milk of mothers who delivered prematurely was higher (2.19 ± 0.88 mmol/L) than that of mothers who delivered at term (1.7 ± 0.86 mmol/L) (p = 0.024). CONCLUSION: Breastfeeding may protect preterm infants against oxidative stress and related disorders in the neonatal period.

Acute necrotizing encephalopathy associated with novel influenza A (H1N1) virus in Turkey.

Influenza-associated acute necrotizing encephalopathy has been well recognized but not yet been reported with novel influenza A in Turkey. We report a 6-year-old boy infected with novel influenza A who displayed the typically characteristic clinical features and neuroimaging findings of acute necrotizing encephalopathy. Physicians who care for children should be aware of acute necrotizing encephalopathy in any child presenting with acute mental status changes during influenza infection. We would like to remind of this entity, because early diagnosis and treatment may reduce mortality and morbidity.

Single enteral loading dose of phenobarbital for achieving its therapeutic serum levels in neonates.

AIM: To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. METHODS: The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 microg/mL were considered as the therapeutic range. RESULTS: The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. CONCLUSION: Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract.

The effect of kangaroo care on pain in premature infants during invasive procedures.

A total of 50 premature infants (25 in KC group, 25 in control group) were included in this comparative, randomized, controlled study. Gestational and postnatal ages of the infants were between 26-36 weeks and 0-28 days, respectively. Infants with congenital abnormalities or sepsis and those who needed mechanical ventilation or surgical intervention were not included in the study. None of the infants received narcotic analgesics. Behavioral and physiologic responses to pain were recorded and Premature Infant Pain Profile (PIPP) was used to evaluate the severity of pain. Collected data was evaluated using SPSS for Windows 11.5 program. Premature Infant Pain Profile scores were significantly lower at each measurement during or soon after the invasive procedure in infants in the KC group compared to controls. In conclusion, KC starting 30 minutes before and continuing 10 minutes after an invasive procedure was found to be effective in decreasing pain during and after the invasive procedure in premature infants.

Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice?

Glutathione S-transferases (GSTs) are a major group of phase II detoxification enzymes involved in the metabolism of both endogenous and xenobiotic compounds. In addition to their catalytic function in detoxification, GSTs participate in binding to nonsubstrate ligands such as bilirubin. Ligandin, which is one of the principal hepatic-binding proteins, is also a member of the GST family. The aim of the present study was to investigate the possible relationship between neonatal jaundice and the GST gene polymorphisms. The study cohort consisted of a patient group of 116 newborns (plasma bilirubin levels > or = 15 mg/dl) and a control group of 54 newborns (plasma bilirubin levels <13 mg/dl). In the patient group, the null genotype frequencies in GSTM1 and GSTT1 were 52.6 and 19%, respectively; in the control group, these were 63 and 27.8%, respectively. The frequencies of GSTM1 and GSTT1 were similar in the patient and control groups (p > 0.05). Total bilirubin levels were found to be significantly higher in patients with the GSTM1 null genotype than in patients with the GSTM1 wild genotype (p = 0.042). There was no statistically significant difference in total bilirubin levels between patients with the null GSTT1 genotype and those with the wild GSTT1 genotype. It is conceivable that there is a relation between GSTM1 gene polymorphism and total bilirubin levels in neonatal jaundice. We suggest that GSTM1 gene polymorphisms may affect ligandin functions in hepatocytes, which are important in bilirubin transportation. Consequently, patients with the GSTM1 null genotype may have higher total levels of bilirubin.

The role of trapidil on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury.

BACKGROUND: Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. Trapidil is an antiplatelet agent and several studies demonstrate the beneficial effect of trapidil in various forms of tissue injury. The effects of trapidil on neuronal apoptosis in HIBI have not been reported previously. AIMS: The aim of this study is to evaluate the effect of trapidil on neuronal apoptosis in neonatal rat model of HIBI. STUDY DESIGN: Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2h. They were treated with trapidil or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia were performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and caspase-3 staining methods. RESULTS: Trapidil treatment either before or after hypoxia results in significant reduction of the numbers of apoptotic cells in both hemispheres, when it is compared with saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups are significantly higher than that in the left hemispheres. CONCLUSIONS: These results show that trapidil administration either before or after hypoxia reduces neuronal apoptosis and we propose that trapidil may be a novel approach for the therapy of HIBI.