Supplementation with Saccharomyces boulardii ameliorates hypoxia/reoxygenation-induced necrotizing enterocolitis in young mice.

Intestinal bacterial proliferation is an important aspect of gastrointestinal injury in neonatal necrotizing enterocolitis (NEC). In the present investigation, we examined the protective action of oral supplementation with Saccharomyces boulardii (S. boulardii), non-pathogen probiotic yeast, against hypoxia-reoxygenation (H/R)-induced NEC in young mice. Young mice were divided into three groups; Group 1 mice (untreated) were subjected only to hypoxia-reoxygenation; Group 2 mice were subjected to hypoxia-reoxygenation and were then given lyophilized S. boulardii (10 mg suspended in 0.5 ml saline) twice a day by orogastric intubation for 10 days. Group 3 mice served as controls. Hypoxia was induced by placing young mice in a 100 % CO (2) chamber for 5 min. After hypoxia, the young mice were reoxygenated for 10 min with 100 % oxygen. We examined the intestinal lesions by light microscopy and measured intestinal generation of PAF and TNF-alpha in the H/R-induced model of NEC. In the probiotic group, NEC-induced intestinal tissue damage was greatly attenuated, with necrosis partially limited to the mucosa. Both intestinal tissue PAF and TNF-alpha concentrations were significantly higher in the untreated group than in controls (p < 0.001). S. boulardii-supplemented young mice showed a significant decrease in intestinal generation of PAF compared with untreated young mice (p < 0.05). On the other hand, no significant difference was observed in the intestinal concentration of TNF-alpha between untreated and probiotic groups ( p > 0.05). The present study suggests that hypoxia/reoxygenation plays an important role in the pathogenesis of NEC and supports hypothesis that especially PAF and TNF-alpha are involved in the pathophysiological mechanism of H/R-induced NEC. This study also demonstrates that dietary supplementation with S. boulardii ameliorates the histologic evidence of H/R-induced intestinal injury. Based on these findings, the beneficial effects of probiotic S. boulardii in this model of NEC are mediated via mechanisms inhibiting intestinal proinflammatory mediator release.

An experimental model of hemolysis-induced acute pancreatitis.

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

An experimental model of hemolysis-induced acute pancreatitis

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20 percent. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20 percent (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20 percent ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70 percent) of 50 rats, moderate hemolysis in seven (14 percent), and no hemolysis in eight (16 percent). Thirty-three of 35 (94.2 percent) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8 percent) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80 percent of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines

The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the generation of platelet-activating factor and leukotriene B4 in hypoxic-ischemic brain in young mice.

Platelet-activating factor (PAF), leukotriene B(4) (LTB(4)) and other cytokines have been indicated to be responsible for the neuronal damage in hypoxic-ischemic brain. Diets in omega-3 (n-3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decrease in active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the effect of dietary supplementation with n-3 fatty acids on endogenous PAF and LTB(4) biosynthesis in hypoxic-ischemic brain of young mice. Young mice were randomly divided into four groups: Group 1 mice were fed standard chow (n-3 polyunsaturated fatty acids free); Group 2 and Group 3 mice were given standard diet supplemented with 10% by weight of fish oil, as source of n-3 polyunsaturated fatty acids, for 3 and 6 weeks, respectively. Group 4 mice served as control. We injured the right cerebral hemisphere of young mice by ligating the right common carotid artery and exposing the mice to 8% oxygen for 60 min. Approximately 10-fold increase in PAF concentration was determined in hypoxic-ischemic brain tissue of Group 1 mice. Tissue concentration of PAF showed a profound decline in Group 3 mice compared to Groups 1 and 2 (P<0.01, P<0.05, respectively). LTB(4) was also significantly elevated in the brain of Group 1 mice when compared to the brain of control mice (P<0.001). A striking decline was observed in the concentration of LTB(4) in both Group 2 and Group 3 mice compared to Group 1 mice (P<0.05, P<0.01, respectively). The present study shows that n-3 fatty-acid-enriched diet inhibits endogenous PAF and LTB(4) generation in hypoxic-ischemic brain tissue; however it demonstrates that 6 weeks of dietary supplementation with n-3 fatty acids results in a significant decrease in tissue level of PAF in the brain.

Intraleucocyte platelet-activating factor levels in desmopressin-treated patients with haemophilia A and von Willebrand disease.

Despite the intensive clinical use of 1-deamino-8-D-arginine vasopressin (desmopressin; DDAVP) for 20 years, its mechanism of action is still not completely explained. It has been proposed that DDAVP stimulates release of a 'second messenger' which in turn stimulates release of von Willebrand factor (vWF) from endothelial cells. Platelet-activating factor (PAF) and interleukin (IL)-6 were individually proposed to be mediators for haemostatic action. The aim of this study was to investigate cellular-based PAF levels in patients with haemophilia A (HA) and von Willebrand disease (vWD) before and after DDAVP treatment and also to look for any probable relationship between the haemostatic response of DDAVP and cellular PAF activities. In total, 20 patients (11 HA and nine vWD) were enrolled in the study. DDAVP was given subcutaneously as a single dose (0.3 microg kg(-1)). Ten patients responded to DDAVP and were defined as the 'able group' (four mild HA, six type 1 vWD). The remaining 10 patients did not respond to DDAVP and were defined as the 'unable group' (seven severe HA, three type 3 vWD). Released (extracellular) and intracellular (intraleucocyte) PAF levels under the stimulation of specific agents (A23187 and Zymosan) were measured by high-performance liquid chromatography and radioimmunoassay. Extracellular and intracellular PAF activities were not detected without stimulation in healthy children whereas significantly higher PAF levels were found in the patients (extracellular: 37.5 +/- 34.4 ng per 10(7) cells; intracellular: 24.8 +/- 23.5 ng per 10(7) cells; P=0.0001). Intracellular PAF levels obtained from in vitro unstimulated cells were significantly higher in DDAVP-responsive (able) patients in comparison to DDAVP-unresponsive (unable) patients (52.1 +/- 18.5 vs. 28.9 +/- 8.0 ng per 10(7)cells). After in vitro stimulation by A23187, intracellular PAF activities were significantly higher in patients than in controls (209.3 +/- 26.1 vs. 172 +/- 18.1 ng per 10(7) cells). Intracellular PAF levels obtained from in vitro stimulated cells by A23187 were also significantly higher in the 'able' patients in comparison to the 'unable' patients (277 +/- 43.5 vs. 225 +/- 30 ng per 10(7)cells). In conclusion, cellular PAF activities are significantly higher in patients with HA and vWD. We also suggest that PAF, especially intracellular PAF mediates intracellular signalling and may be one of the important mediators for the haemostatic response of DDAVP.

Levels of leukotriene B4 in gingival crevicular fluid and gingival tissue in specific periodontal diseases.

BACKGROUND: Leukotriene B4 (LTB4), a product of the lipoxygenase pathway of arachidonic acid metabolism, exhibits numerous activities that can account for most of the features of host responses seen in periodontal diseases. The aim of the present study was to examine the role of LTB4 in the pathogenesis of specific periodontal diseases. METHODS: LTB4 levels were investigated in gingival crevicular fluid (GCF) and gingival tissue (GT) samples of 10 patients with chronic periodontitis (CP), 12 patients with generalized aggressive periodontitis (GAgP), 6 patients with localized aggressive periodontitis (LAgP), 6 patients with gingivitis (G), and 6 periodontally healthy subjects (H). Periodontal status was evaluated by measuring probing depth, gingival index, papillary bleeding index, and plaque index. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and was purified by high performance liquid chromatographic method and then analyzed by radioimmunoassay. RESULTS: All patient groups had significantly higher levels of GCF and GT LTB4 compared to the control group (P<0.005). The CP patients had the highest LTB4 levels compared to those in other patient groups (P<0.005). GAgP, LAgP, and G groups had similar amounts of GCF and GT LTB4 (P>0.005). When the data were expressed as concentration, the CP group was found to have higher concentration of LTB4, compared to that of control group (P<0.005). GAgP, LAgP, and G groups had similar LTB4 concentration compared to that of control group (P>0.005). No significant difference was found between GAgP, LAgP, and G groups (P>0.005). The CP group had higher LTB4 concentration compared to both GAgP and LAgP groups (P<0.005). Although the CP group had a higher GCF LTB4 concentration compared to G group, this difference did not reach significance (P>0.005). No significant correlation was found between GCF and GT LTB4 levels and clinical parameters. CONCLUSIONS: The results of the present study indicate that LTB4 is likely to be an important mediator in regulating inflammatory responses in the human periodontal tissues. This lipid mediator may play an important role in the pathophysiology of periodontal disease.

Levels of platelet-activating factor in gingival crevicular fluid and gingival tissue in specific periodontal diseases.

BACKGROUND: Platelet-activating factor (PAF), a potent phospholipid mediator of inflammatory and immune reactions, is involved in a variety of biological responses seen in periodontal diseases. The aim of the present study was to examine the role of PAF in the pathogenesis of specific periodontal diseases. METHODS: PAF levels were investigated in gingival crevicular fluid (GCF) and gingival tissue (GT) samples of 12 patients with generalized aggressive periodontitis (GAgP), 6 patients with localized aggressive periodontitis (LAgP), 10 patients with chronic periodontitis (CP), 6 with gingivitis (G), and 6 periodontally healthy subjects (H). Periodontal status was evaluated by measuring probing depth, gingival index, papillary bleeding index, and plaque index. PAF was extracted from GCF samples passing through amberlit resin columns, purified by high performance liquid chromatographic method, and then analyzed by radioimmunoassay. RESULTS: GAgP, LAgP, and CP groups had significantly higher GCF PAF levels compared to the H group (P<0.005). Although statistically not significant, GCF PAF levels were also higher in the G group than those of the H group (P = 0.0784). GAgP, LAgP, and CP groups had similar GCF PAF levels (P>0.005). These groups had higher levels of GCF PAF than those of the G group, but the difference was significant only for the GAgP group (P<0.005). When the data were expressed as concentration, GAgP, LAgP, and CP groups were found to have higher concentrations of GCF PAF compared to the H group (P<0.005). GCF PAF concentration was similar in patient groups (P>0.005). All patient groups had significantly higher GT PAF levels compared to the H group (P<0.005). GAgP, LAgP, and CP groups had similar amounts of GCF and GT PAF (P>0.005). GAgP, LAgP, and CP groups had higher GT PAF levels than those of the G group, but the differences were only significant for LAgP and CP groups (P<0.005). No significant correlation was found between GCF and GT PAF levels and clinical parameters. CONCLUSIONS: The results of the present study indicate that PAF is likely to be an important mediator in regulating inflammatory responses in the human periodontal tissues. To our knowledge, this is the first report investigating PAF levels in GCF and GT in specific periodontal diseases. We believe that this potent phospholipid mediator may need to be considered in the pathogenesis of periodontal diseases.

Is mannitol effective against platelet-activating factor (PAF)-induced liver damage in obstructive jaundice?

BACKGROUND/AIMS: Platelet-activating factor, is a unique phospholipid with a broad range of biological activities that may be relevant in the development of inflammatory reactions. Platelet-activating factor has been suspected to play an important role in liver pathophysiology. The cultured Kupffer and endothelial cells produce and release platelet-activating factor in order to facilitate communication between hepatic sinusoidal and parenchymal cells. In this study, in the experimental jaundice model, platelet-activating factor levels were measured in liver tissue and plasma and the possible effects of mannitol on this mediator were assessed. METHODOLOGY: The experimental model consisted of 7 rats in the control group (CG), 7 rats in the sham operation group (ShG), and 7 rats in the obstructive jaundice group (JG) created by ligating the common bile duct. The last group was the mannitol-treated jaundiced group (MJG) and all animals in this group received 20% mannitol in doses of 2 mL/day, intraperitoneally, following common bile duct ligation. A week later all animals were sacrificed and plasma and liver tissue samples were collected. Platelet-activating factor levels were measured by radioimmunoassay technique. RESULTS: Liver tissue platelet activating factor levels (pg/mg tissue protein) were 72 +/- 18 in the CG, 183 +/- 51 in the JG, 84 +/- 17 in ShG, and 124 +/- 36 in MJG. Plasma levels were 460 +/- 13, 1600 +/- 40, 560 +/- 19, and 1200 +/- 23, respectively. In both sample types, MJG and JG values were significantly different from CG and ShG as well. MJG levels were also different from JG. CONCLUSIONS: These results showed that plasma and liver tissue platelet-activating factor levels are increased in experimental obstructive jaundice; and activation of this mediator contributes to the ongoing liver injury. Mannitol may improve or lessen this damage.

Plasma and liver carnitine status of children with chronic liver disease and cirrhosis.

BACKGROUND: Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane for oxidation. As its synthesis is performed in the liver, alterations in carnitine metabolism is expected in liver diseases, especially in cirrhosis. METHODS: In this study, we investigated plasma and liver carnitine concentrations of 68 children with chronic liver disease, 36 of whom had cirrhosis as well. Carnitine level was determined by enzymatic method. RESULTS: Plasma and liver carnitine concentrations were not correlated. Mean plasma carnitine level of cirrhotic children was significantly lower than that of the control group (P<0. 0001). While there was no difference between liver carnitine concentrations of children with chronic liver disease and cirrhosis (P>0.05), mean plasma level of cirrhotics were lower (P<0.05). Plasma carnitine was correlated with albumin, triglyceride and gamma glutamyl transpeptidase (GGT) in patients with chronic liver disease (P<0.05). Liver carnitine was correlated with GGT in cirrhotic patients (P<0.005). Children with malnutrition had higher plasma and liver carnitine levels (P<0.05). The highest plasma and liver carnitine levels were detected in children with biliary atresia and criptogenic cirrhosis, respectively. Both the lowest plasma and liver carnitine levels were detected in Wilson's disease. CONCLUSION: Children with cirrhosis have low plasma carnitine concentrations. This finding is prominent in children with Wilson's disease. As carnitine is an essential factor in lipid metabolism, the carnitine supplementation for patients with cirrhosis in childhood, especially with Wilson's disease, seems to be mandatory.

Levels of leukotriene B4 and platelet activating factor in gingival crevicular fluid in renal transplant patients receiving cyclosporine A.

BACKGROUND: Cyclosporine A (CsA) is a potent immunosuppressant effectively used to prevent organ transplant rejection and also to treat several systemic diseases. CsA-induced gingival overgrowth (CsA GO) is the most widely seen side effect of this drug; its pathogenesis is not completely understood. The aim of the present study was to identify the role of leukotriene B4 (LTB4) and platelet activating factor (PAF) in the pathogenesis of CsA GO. METHODS: LTB4 and PAF levels were detected in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO, from patients with gingivitis and from periodontally healthy subjects. Plaque index, papilla bleeding index, and hyperplastic index were recorded at each study site. GCF samples and clinical data were obtained from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and purified by high-performance liquid chromatographic (HPLC) method and analyzed by radioimmunoassay (RIA). PAF was extracted from GCF samples passing through amberlit resin columns, purified by HPLC, and analyzed by RIA. RESULTS: Total amounts of LTB4 and PAF in GCF were higher in CsA GO+ sites compared to the healthy sites from healthy controls. However, the amount of LTB4 and PAF elevation in CsA GO+ sites was not significantly higher than those in diseased sites. Clinical degrees of gingival inflammation were also similar between CsA GO+ and diseased sites. LTB4 and PAF total amounts in GCF were higher in CsA GO+ sites compared to CsA GO- sites in the same subjects, but this difference just failed to reach significance. Similar findings were obtained with concentration data. CONCLUSIONS: The results of this study indicate that CsA therapy does not have a significant effect on GCF LTB4 and PAF levels and that gingival inflammation seems to be the main reason for their elevation. In CsA-treated patients, alterations in LTB4 and PAF levels might play a role in CsA GO through some asyet unknown mechanism. To our knowledge, this is the first report describing the levels of lipid mediators in GCF of CsA-treated patients. We assume that further studies will contribute to the understanding of the pathogenesis of CsA-induced gingival overgrowth.

Role of leukotrienes on coronary vasoconstriction in isolated hearts of arthritic rats: effect of in vivo treatment with CI-986, a dual inhibitor of cyclooxygenase and lipoxygenase.

In this study, coronary perfusion pressure and force of contraction were investigated in isolated hearts removed from arthritic rats by using the Langendorff method. A strong coronary vasoconstriction was determined in arthritic hearts which was associated with elevated levels of arachidonate 5-lipoxygenase (5-LOX) products, leukotriene B(4) (LTB(4)) and LTC(4) in coronary effluents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) and LOX, CI-986 (2 and 10 mg/kg/day) on days 14- 26 following adjuvant injection, prevented the coronary vasoconstriction and the increased production of LTB(4) and LTC(4). These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries.

Lymphocyte subsets and inflammatory mediators in patients with subacute sclerosing panencephalitis.

A defective cell-mediated immunity and inflammatory cytokines are suggested in the pathogenesis of subacute sclerosing panencephalitis. In this study we analyzed lymphocyte subsets in peripheral blood and concentrations of interleukin-1alpha (IL-1alpha), interleukin-2 (IL-2alpha), tumor necrosis factor-alpha (TNF-alpha), and platelet activating factor in plasma and cerebrospinal fluid before and after immunomodulatory therapy (interferon-alpha plus isoprinosine) in three patients with subacute sclerosing panencephalitis. Increased percentage of CD8+cells (T-suppressor/cytotoxic cell) and CD16+CD56+cells (NK cell) and reduced percentage of CD3+/HLA-DR+ (active T-cell) and CD3+ (total T-cell) cells were found before therapy. After immunomodulatory therapy, CD3+/HLA-DR+ (active T-cell) cells were markedly increased and there was a slight increase in the percentages of all lymphocyte subsets in the patients. The concentrations of platelet activating factor in plasma and cerebrospinal fluid were higher than the mean value in controls. Cerebrospinal fluid and plasma TNF-alpha and IL-2 levels were nondetectable in two patients who had a stationary course of disease and were markedly elevated in patient 3, who displayed a rapidly progressive course.

Platelet-activating factor concentrations in healthy and septic neonates.

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). Platelet-activating factor levels increase upon stimulation by Gram negative bacteraemia and are a important mediator of neonatal sepsis.

Increased gastric production of platelet-activating factor, leukotriene-B4, and tumor necrosis factor-alpha in children with Helicobacter pylori infection.

The concentrations of platelet-activating factor (PAF), leukotriene-B4 (LTB4), and tumour necrosis factor-alpha (TNF-alpha) in homogenate supernatants of gastric mucosal biopsy specimens and in gastric juice from Helicobacter pylori-positive (N = 21) and -negative children (N = 14) were investigated in order to determine whether these lipid mediators and the cytokine are involved in the inflammatory reaction of H. pylori-associated gastritis. PAF and LTB4 concentrations were measured after high-performance liquid chromatography (HPLC) purification by specific radioimmunoassay, and TNF-alpha concentrations were determined by using an enzyme-linked immunosorbent assay. The concentrations of PAF, LTB4, and TNF-alpha measured in gastric juice and biopsy homogenate supernatants of children with H. pylori-positive gastritis were found to be statistically elevated and in positive correlation with each other. This study suggested that increased local mucosal production of potent proinflammatory agents such as PAF, LTB4, and TNF-alpha may be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.

Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats?

We investigated the protective role of fish oil (FO-source of n-3 FA) enriched diet (in the first protocol) in 20 rats and FO administration intrarectally (in the second protocol) in 40 rats with trinitrobenzene (TNB) colitis. All colonic specimens were pathologically evaluated, myeloperoxidase enzyme activities were measured, leukotriene B4 (LTB4) and LTC4 levels were determined by radioimmunoassay. In the first protocol 10 rats (group A1) were fed with 8% sunflower and cotton oil enriched diet and (group A2) with 8% FO enriched diet for 6 weeks. At the end of this period, TNB (30 mg in 0.25 ml of 30% ethanol) were intrarectally administered. After 2 weeks, rats were sacrificed. MPO activities (2.47 versus 30.17), LTB4 (34.5 versus 903.3) and LTC4 (77.7 versus 456.0) levels were significantly reduced in group A2 compared with group A1 (P<0.005). There was also a significant difference in pathologic scores (1.55 versus 2.12, P<0.002) between two groups. In the first part of the second protocol, 20 male rats were randomized into two equal groups (B1 and B2) and TNB colitis was induced. After 1 day, 1 ml of saline (group B1) or n-3 FA enemas (group B2) were administered every day for 2 weeks. At the end of this period, rats were sacrificed and evaluated as done for previous groups. Although there was no significant difference between the two groups in comparison with MPO enzyme activities and pathologic scores, the LTB4 (130.1 versus 971.0) and LTC4 (126.0 versus 532.0) levels of FO group were significantly reduced (P<0.005). In the second part of the second protocol, 20 male rats were randomized into two groups. One millilitre of saline (group B3) or FO enemas (group B4) were administered to rats every day for 3 days. At the fourth day, TNB-colitis was induced and after 24 h rats were sacrificed. We could not find any significant difference in MPO activities, pathologic scores, LTB4 and LTC4 levels between groups B3 and B4. In conclusion, FO enriched diet decreased both pathologic damage and tissue LT levels. The second protocol of our study revealed that the long-term FO enemas decreased the LTB4 and LTC4 levels; however, did not have any beneficial effect on the tissue lesions. Short periods of FO enemas did not have a protective role in the occurrence of experimental colitis. The present study showed that FO enemas significantly decreased LT levels. The protective effect of FO (oral and enema) in TNB colitis may open a new insight into the treatment of inflammatory bowel disease.

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

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. METHODS: Therefore, we conducted a study in newborns with perinatal asphyxia to try to show the relationship between the clinical severity and plasma PAF levels. RESULTS: Mean plasma levels of 19 asphyxiated infants (997.8 +/- 363.5 pg/mL) were significantly higher than that of 20 healthy infants (410.2 +/- 148.6 pg/mL, P < 0.0001). Patients with clinically severe HIE had significantly higher levels of PAF (1494.2 +/- 386.6 pg/mL) when compared with patients with mild HIE (815 +/- 114.5 pg/mL) and with moderate HIE (828.3 +/- 61.1 pg/mL). There was a significant correlation between plasma PAF concentration and arterial pH and base deficit, but no correlation with platelet and leukocyte counts. CONCLUSIONS: Plasma PAF levels correlating with the severity of HIE is interpreted to mean that high PAF levels may be an indicator of clinical severity and probably the poorer prognosis of patients with HIE.

The effect of L-carnitine on platelet activating factor concentration in the immature rat model of hypoxic-ischemic brain injury.

Recent data suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. We investigated brain tissue PAF concentration in the hypoxic-ischemic brain of immature rats. Endogenous PAF concentration in brain tissue showed a marked increase in hypoxic-ischemic pups (Group 1, 85.6 +/- 15.5 pg/mg protein) when compared to that of the control (9.1 +/- 3.1 pg/mg protein). In addition, we studied the effects of pretreatment with L-carnitine (5 days and 2 h before the hypoxia) on endogenous PAF concentration in the hypoxic-ischemic brain. Endogenous PAF concentration in the short-term pretreatment group (Group 2, 81.6 +/- 9.7 pg/mg protein) was not different than in Group 1 rat pups. However, a significantly decreased PAF concentration was found in the group of pups that received carnitine pretreatment for 5 days (Group 3, 30.5 +/- 11.0 pg/mg protein). These results indicate that PAF is an important mediator in the immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of L-carnitine on PAF production may give new insight into the treatment of hypoxic-ischemic brain injury.

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.

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.