Isil Coker

Platelet-activating factor is an important mediator in hypoxic ischemic brain injury in the newborn rat: Flunarizine and Ginkgo biloba extract reduce PAF concentration in the brain

Hypoxic-ischemic encephalopathy is still a very important cause of neonatal mortality and morbidity. Recently, platelet-activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic-ischemic brain. We investigated tissue PAF concentrations in hypoxic-ischemic brain injury in immature rats. Endogenous PAF concentration in brain tissue showed a marked increase in hypoxic-ischemic pups (85.6 ± 15.5 pg/mg protein) when compared to that of control (9.05 ± 3.1 pg/mg protein). In addition, we examined the effects of flunarizine, a selective calcium channel blocker, and Ginkgo biloba extract (EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain injury. Endogenous PAF concentrations in both flunarizine-pretreated (16.6 ± 4.8 pg/mg protein) and EGb 761-pretreated (33.5 ± 8.9 pg/mg protein) pups were significantly lower than the untreated group. These results indicate that PAF is an important mediator in immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of flunarizine and EGb 761 on PAF production may open new insight into the treatment of hypoxic-ischemic brain injury.

Effect of dietary n-3 fatty acids on hypoxia-induced necrotizing enterocolitis in young mice. n-3 fatty acids alter platelet-activating factor and leukotriene B4 production in the intestine.

Necrotizing entercolitis (NEC) is an important neonatal disease with a high mortality rate. Inflammatory mediators, such as mainly platelet-activating factor (PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the genesis of NEC. Diets in Ω–3 (n–3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decreased active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the protective effect of fish oil (source of n–3 fatty acids) on hypoxia-induced model of NEC. Young mice were divided into three groups; group 1 mice were fed standard chow (n–3 fatty acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks. Group 3 mice served as control. We examined the intestinal lesions by light microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced model of NEC. Significantly increased intestinal PAF and LTB4 levels were found in group 1 mice when compared to group 2 and group 3 mice. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury. In the n–3 fatty acids-supplemented animals these lesions were milder. The present study shows that endogenously released PAF and LTB4 play an important role in mediating hypoxia-induced intestinal necrosis. The present study also suggests that dietary supplementation with n–3 fatty acids suppress intestinal PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal protective effect of n–3 fatty acids in an experimental model of NEC may open new insight into the treatment and preventation of NEC in neonates.

Increased Gastric Production of Platelet-Activating Factor, Leukotriene-B4, and Tumor Necrosis Factor-α in Children with Helicobacter pylori Infection

The concentrations of platelet-activating factor(PAF), leukotriene-B4 (LTB4), andtumour necrosis factor-α (TNF-α) inhomogenate supernatants of gastric mucosal biopsyspecimens and in gastric juice from Helicobacter pylori-positive (N =21) and-negative children (N = 14) were investigated inorder to determine whether these lipid mediators and thecytokine are involved in the inflammatory reaction of H. pylori-associated gastritis. PAF andLTB4 concentrations were measured afterhigh-performance liquid chromatography (HPLC)purification by specific radioimmunoassay, andTNF-α concentrations were determined by using an enzyme-linkedimmunosorbent assay. The concentrations of PAF, LTB, andTNF-α measured in gastric juice and biopsyhomogenate supernatants of children with H. pyloripositive gastritis were found to be statisticallyelevated and in positive correlation with each other.This study suggested that increased local mucosalproduction of potent proinflammatory agents such as PAF, LTB4, and TNF-α may beimplicated in the pathogenesis of H. pylori-associatedgastritis in childhood.

Platelet-activating factor concentrations in healthy and septic neonates

Abstract Platelet-activating factor levels were measured in nine preterm infants with Klebsiella pneumonia septicaemia, eight healthy preterm infants of similar gestational age and ten healthy full-term infants of the same postnatal age at sampling. The platelet-activating factor levels of the healthy preterm and term groups did not differ significantly, but were elevated compared to the other two groups in the septic preterm infants (P < 0.01). Conclusion Platelet-activating factor levels increase upon stimulation by Gram negative bacteraemia and are a important mediator of neonatal sepsis.

Plasma platelet-activating factor levels in newborn infants with and without perinatal asphyxia : Is it an additional marker of perinatal asphyxia?

Abstract Background: Hypoxic‐ischemic encephalopathy (HIE) is still a very important cause of neonatal mortality and morbidity. Recently platelet‐activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic‐ischemic brain.

Effect of hemodialysis on carnitine levels in children with chronic renal failure

Background : Impaired structural and metabolic integrity of the kidney in chronic renal failure (CRF) effects carnitine metabolism by means of many factors. Depletion due to hemodialysis (HD) is one of the major concerns. The aim of the study was to investigate the effects of chronic renal failure and HD on plasma free carnitine (FC) concentrations in children.

Platelet-Activating Factor Levels in Term and Preterm Human Milk

It is well known that necrotizing enterocolitis (NEC) is less frequent in newborns being fed human breast milk. Since recent studies indicated that platelet-activating factor (PAF) plays an important role in pathogenesis of NEC, this study was conducted to investigate the PAF levels in human milk. Colostrum and mature human milk (samples obtained in the third week) of three groups of mothers were investigated. The first group had given birth within less than 32 weeks, the second between 33–37 weeks and the third group after 38 weeks of gestation. The PAF levels in colostrum of all three groups were similar (0.95 ± 0.57, 1.05 ± 0.52 and 1.19 ± 0.64 ng/ml, respectively). Mature human milk in groups I and II had similar PAF levels (1.16 ± 0.54 and 1.21 ± 0.60 ng/ml, respectively), however, mature human milk in group III had a significantly higher PAF concentration (2.04 ± 0.59 ng/ml) than both groups’ levels. However, this phenomenon by itself does not explain the protective effect of human milk against NEC.

Plasma and urinary platelet activating factor concentrations and leukotriene releasing activity of leukocytes in steroid sensitive nephrotic syndrome of childhood

Platelet activating factor (PAF) is synthesized and secreted by glomerular mesangial and endothelial cells. It increases glomerular basement membrane permeability and induces proteinuria. Leukotrienes (LT) are mediators released by either leukocytes or glomerular cells under the PAF effect. The possible role of PAF in steroid sensitive nephrotic syndrome (SSNS) of childhood was studied in 8 children with SSNS in the acute stage, 5 children in remission and 8 healthy controls. The PAF concentrations in urine and plasma were determined. Leukocytes were stimulated in vitro and the LT release in response to stimulation was determined. The urinary and plasma concentrations of PAF were significantly higher in the acute phase than in remission and in control patients. Children with SSNS were found to have peripheral leukocytes with increased LT releasing activity in vitro. These results are in accordance with clinical and experimental observations indicating that PAF originates in the kidney and plays a role in normal kidney physiology. Urinary PAF concentrations may be related to proteinuria because they were strongly correlated in the present study. Elevated plasma PAF concentrations in the acute stage of SSNS could result from either its secretion from the circulating leukocytes or decreased acetyl hidrolase activity needed for its hydrolysis in plasma. The increased LT release in vitro suggests that these cells might have been activated by PAF secreted from glomeruli. It is proposed that PAF and different LT in systemic and glomerular circulation are important mediators in childhood SSNS.

Myocardial and Hepatic Free Carnitine Concentrations in Pups of Diabetic Female Rats

Background/Aims: Adequate carnitine levels are required for normal fatty acid and energy metabolism in heart muscle. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency and that carnitine therapy may be beneficial to the diabetic heart. Infants of diabetic mothers (IDM) are known to be at risk for developing a hypertrophic type of cardiomyopathy. In the present investigation, we examined the free carnitine concentration from cardiac and hepatic tissue in pups of streptozotocin-induced diabetic female rats. We also assessed the effect of maternal L-carnitine supplementation on the free carnitine concentration in pups of diabetic rats. Method: Three groups, each consisting of 4 Wistar albino female rats, were studied, Group 1 (untreated diabetic; n = 4) and group 2 (L-carnitine-treated diabetic; n = 4) rats were given streptozotocin (60 mg/kg) by intraperitoneal injection; group 3 were controls. During pregnancy, L-carnitine was given at a dose of 150 mg/kg by intraperitoneal injection once a day for 14 days. Cesarean section was carried out, and 113 newborn rats (group 1 n = 36; group 2 n = 38; group 3 n = 39) were obtained from all the pregnant rats. Results: The free carnitine concentration in myocardial tissue was significantly decreased in the female diabetic rats (p < 0.001). However, the free carnitine concentration from hepatic tissue in diabetic female rats was similar to that in controls. In pups of group 1 diabetic rats, a significantly decreased free carnitine concentration was found in both myocardial and hepatic tissue compared to group 2 and controls. The free carnitine content from myocardial and hepatic tissue was significantly elevated in the maternal L-carnitine-supplemented group when compared to group 1 and control pups (p < 0.001 and p < 0.05, respectively). Conclusions: The present study has demonstrated that the free carnitine concentration from myocardial and hepatic tissue is significantly reduced in pups of streptozotocin-induced diabetic female rats. This study has also shown that administration of maternal L-carnitine improves the carnitine level in pups of diabetic rats. A decreased myocardial carnitine concentration may be partly responsible for the development of cardiomyopathy in IDM.

Free carnitine levels in children with steroid–sensitive nephrotic syndrome

Background : Carnitine transports long‐chain fatty acids accross the inner mitochondrial membrane. Carnitine metabolism is disturbed in some renal diseases, such as chronic renal failure. Previous studies have shown that children had normal serum free carnitine (FC) and total carnitine levels in idiopathic nephrotic syndrome, IgA nephropathy, non‐IgA nephropathy and focal segmental glomerulosclerosis. The aim of the present study was to determine FC concentrations in plasma and urine during acute and remission periods of steroid‐sensitive nephrotic syndrome (SSNS) and its association with hyperlipidemia.