Bone mineral status in pediatric outpatients on antiepileptic drug monotherapy.

Drug-induced osteopenia has been reported in institutionalized children on chronic antiepileptic drug therapy. The aim of this study was to assess longitudinally bone mineral status in pediatric outpatients on antiepileptic drug monotherapy. The study group consisted of 30 ambulatory children on a normal diet: 15 on valproic acid, 11 on carbamazepine, and 4 on phenobarbital monotherapy. Bone mineral density, serum active vitamin D (1,25-dihydroxyvitamin D), and certain biochemical markers of bone formation (calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, osteocalcin, calcitonin, and urinary calcium to serum creatinine and urinary phosphorus to serum creatinine ratios) were studied at the beginning of antiepileptic drug monotherapy and at the end of 2 years of treatment. Age- and sex-specific Z-scores of bone mineral density were measured at anterior-posterior L2-L4 by dual-energy x-ray absorptiometry. Drug-induced osteopenia was defined in only two patients (one on carbamazepine and the other on phenobarbital monotherapy), with Z-scores of bone mineral density less than -1.5. Serum levels of active vitamin D and biochemical markers were not significantly correlated with the Z-scores of bone mineral density. We detected a frequency of antiepileptic drug-induced osteopenia of 6.7% in pediatric outpatients after 2 years of monotherapy. However, osteopenia was not attributed to a defect in serum active vitamin D production owing to hyperparathyroidism in children on antiepileptic drug monotherapy.

Adjunctive subantimicrobial dose doxycycline: effect on clinical parameters and gingival crevicular fluid transforming growth factor-beta levels in severe, generalized chronic periodontitis.

BACKGROUND: At present there is limited data concerning the efficacy of non-surgical periodontal therapy supplemented with subantimicrobial dose doxycycline (SDD) in the treatment of severe, generalized periodontitis. The purpose of the present study was to evaluate the effect of adjunctive SDD therapy on clinical periodontal parameters and gingival crevicular fluid (GCF) transforming growth factor-beta1 (TGF-beta1) levels in patients with severe, generalized chronic periodontitis over a 6-month period. METHODS: Thirty-five patients with severe, generalized periodontitis and 11 periodontally healthy subjects were included in the present study. Patients received full-mouth supragingival debridment at baseline and randomized to take either SDD b.i.d. or placebo b.i.d. for 3 months. Patients received root planing and oral hygiene instruction once a week for four consecutive weeks. Clinical measurements including probing depth (PD), clinical attachment level, papilla bleeding index and plaque index and GCF sampling were performed at baseline, 3 and 6 months. The GCF TGF-beta1 levels were analysed by enzyme-linked immunosorbent assay. RESULTS: Thirteen patients in both study groups completed the 6-month trial. Following scaling and root planing (SRP) plus SDD and SRP plus placebo therapy significant improvements in clinical periodontal parameters of both groups were observed (p<0.025). In the SDD group a significantly higher percentage (%73.4) of deep pockets resolved (PD reduction > or =3 mm from baseline) when compared with placebo group (%49.7) at 6 months (p<0.05). At baseline there were no significant differences in GCF TGF-beta1 levels between three groups. Both total amount and concentration of GCF TGF-beta1 in SDD and placebo groups increased when compared with baseline at 3 months. However, only GCF TGF-beta1 levels of SDD group was significantly higher than baseline (p<0.025) and placebo group (p<0.017) at 3 months. At 6 months GCF TGF-beta1 levels of both groups were similar to baseline levels (p<0.025). CONCLUSIONS: These data indicate that combination of SDD with non-surgical therapy improves clinical parameters of periodontal disease and increases GCF TGF-beta1 levels together with a decrease in prevalence of residual pockets in patients with severe, generalized chronic periodontitis. Increased GCF TGF-beta1 levels following SDD therapy might suggest a novell pleiotrophic mechanism for tetracyclines to inhibit connective tissue breakdown.

Platelet-activating factor and P-selectin activities in thrombotic and nonthrombotic Behçet's patients.

OBJECTIVE: The aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behçet's disease patients with and without thrombosis. METHODS: In this cross-sectional and descriptive study, 30 consecutive Behçet's patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma DeltaCD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated. RESULTS: In the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and DeltaCD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behçet's patients, there was a positive correlation between plasma PAF and DeltaCD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and DeltaCD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone. CONCLUSION: Platelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behçet's disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.

Gingival crevicular fluid monocyte chemoattractant protein-1 and RANTES levels in patients with generalized aggressive periodontitis.

BACKGROUND: Local and systemic inflammatory and immune mechanisms may be implicated in the pathogenesis of the aggressive forms of periodontal disease. Chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cells expressed and secreted RANTES (regulated on activation, normal T cells expressed and secreted), are involved in the activation and recruitment of inflammatory and immune cells to the infected sites and thereby mediating a variety of pathophysiological conditions. The aim of the present study was to examine the gingival crevicular fluid (GCF) levels of MCP-1 and RANTES in patients with generalized agressive periodontitis (G-AgP). METHODS: MCP-1 and RANTES levels were investigated in GCF samples of 10 patients with G-AgP and 10 periodontally healthy subjects. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, presence of bleeding on probing and plaque. In the G-AgP group, GCF samples were collected from the two approximal sites; from one single-rooted tooth and from one first molar tooth with > or =6 mm probing depth. In the healthy group, GCF samples were collected from one of the single-rooted teeth. GCF MCP-1 and RANTES levels were quantified by enzyme immunoassay. RESULTS: The G-AgP patients had significantly higher GCF MCP-1 and RANTES levels compared to the healthy group (p<0.05). GCF MCP-1 and RANTES levels were positively correlated with both probing depth and clinical attachment loss (p<0.05). There was no correlation between GCF MCP-1 and RANTES levels and the percentage of sites with bleeding (p>0.05). CONCLUSIONS: The results of the present study suggest that MCP-1 and RANTES could play key roles in both activation and recruitment of inflammatory and immune cells in periodontal environment of G-AgP patients. In conclusion, these CC chemokines may be considered in the biological mechanism underlying the pathogenesis and progression of G-AgP.

Tumor necrosis factor alpha and interleukin 6 productions in response to platelet-activating factor in chronic hepatitis B virus infection.

OBJECTIVE: The aim of this study was to determine tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) release in response to platelet-activating factor (PAF) induction in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis B virus (HBV) carriers. METHODS: Subjects were grouped into three subgroups. The mean age was 37 +/- 10 years. Group A (n = 15), group B (n = 10) and group C (n = 9) subjects were HBV serology-negative, had natural immunity after recovery from an acute HBV infection, and were chronic HBV carriers, respectively. RESULTS: Compared with group A, PBMCs from naturally immune subjects and chronic HBV carriers produced significantly higher amounts of TNF-alpha and IL-6 in response to PAF. In chronic HBV carriers, TNF-alpha (1,633.3 +/- 793.7) and IL-6 (2,533.3 +/- 466.3) production was statistically lower than TNF-alpha (2,630.0 +/- 727.3) and IL-6 (3,870.0 +/- 728.4) obtained from naturally immune subjects to HBV. CONCLUSION: Differences of TNF-alpha levels between chronic HBV carriers and naturally immune subjects suggest that TNF-alpha may be a critical mediator of HBV clearance.

The role of dietary supplementation with L-glutamine in inflammatory mediator release and intestinal injury in hypoxia/reoxygenation-induced experimental necrotizing enterocolitis.

BACKGROUND/AIMS: Necrotizing enterocolitis (NEC) is a multifactorial syndrome in the neonate. Enteral feeding practices are an important component of gastrointestinal injury in neonatal NEC. In the present study, we examined the protective effect of oral supplementation with L-glutamine, an important specific fuel for the enterocytes, against hypoxia-reoxygenation (H/R)-induced NEC in young mice. METHODS: Young mice were divided into four groups: group 1 mice (untreated) underwent H/R; group 2 mice were supplemented with L-glutamine in drinking water (0.5 g/dl) for 3 days, and group 3 mice were supplemented with L-glutamine (3 g/dl) for 10 days. Group 4 mice served as control. Hypoxia was induced by placing the young mice in a 100% CO(2) chamber for 5 min. After hypoxia, they were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions with light microscopy and measured intestinal generation of PAF and TNF-alpha in the H/R-induced model of NEC. RESULTS: In group 3 mice, NEC-induced intestinal tissue damage was greatly attenuated with necrosis limited partially to the mucosa. Both intestinal tissue PAF and TNF-alpha concentrations were significantly higher in the untreated group than in controls (p < 0.001). Group 3 mice (3 g/dl supplemented) showed a significant decrease in intestinal TNF-alpha concentration compared with young group 1 and group 2 mice (p < 0.05 and p < 0.05, respectively). On the other hand, no significant difference was observed in the intestinal generation of PAF between H/R groups (p > 0.05). CONCLUSION: The present study suggests that H/R plays an important role in the pathogenesis of NEC and supports the 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 L-glutamine reduces the histologic evidence of H/R-induced intestinal injury. Based on these findings, beneficial effects of L-glutamine in this model of NEC are mediated via mechanisms inhibiting intestinal cytokine release.

Effects of hepatectomy and arginine enriched diet on colonic mucosa originated inflammatory cytokines.

AIM: To assess the effects of arginine-enriched diet and partial hepatectomy in rats on gut-originated inflammatory cytokines. METHODS: Of 24 rats, Group 1 and 2 animals were fasted 24 hours before surgery, Group 3 and 4 animals received regular plus arginine-enriched diet(AED). Group 2 and 4 animals had undergone 30% hepatic resection. Leukotriene B4 (LT B4) levels were detected in colonic mucosa and mucosal perfusates immediately after resection. Mean leukocyte counts (MLC) were detected also in the mucosa. RESULTS: In the basis of fasting situation regardless hepatectomy, all MLC were lower in Group 3 and 4 but LTB4 levels both in mucosa and perfusate were higher. On hepatectomy based comparison there was not any statistically significant difference between groups but mucosal perfusate LTB4 levels. But when hepatectomy added on fasted animals MLC levels were lower than fed by AED + sham operation. LTB4 levels were insignificant in both perfusate and mucosa. When hepatectomy added on AED animals (Group 4), MLC decreased and mucosal LTB4 increased when they compared with fast without hepatectomy Group 1. CONCLUSIONS: AED prior to extra-intestinal operations may trigger inflammatory cascade and complications via leucocyte degradation and LTB4.

Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia.

Hypoxic-ischemic encephalopathy (HIE) remains one of the most important neurologic complications in the newborn. Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage. Furthermore, recent data have suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia. In addition, we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid (CSF) after hypoxic-ischemic brain injury. The group of asphyxiated infants (Group 1) consisted of 21 full-term (gestational age >37 weeks). These infants were randomized and divided into either a standard therapy group (Group 1a; n=10) or cooling group (Group 1b; n=11). Head cooling combined with minimal hypothermia (rectal temperature 36.5-36 degrees C) was started as soon as practicable after birth. The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h. The control group (Group 2) consisted of seven full-term infants and none of these infants showed any sign of asphyxia. To measure PAF concentration in CSF, CSF with lumbar puncture was collected into tubes immediately before the cooling (1-3h after birth) and again after 36h. We had no evidence of severe adverse events related to hypothermia. In Group 1a, two infants died after 72h of life; however, all newborn infants in Group 1b survived. Convulsion required treatment in three infants of standard therapy group (1a); none of the infants in Group 1b had clinical seizure activity. Abnormal EEG patterns were found in four infants of Group 1a; no EEG abnormalities were noted in Group 1b (P<0.05). On admission (before cooling), PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control (P<0.001). Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups (Group 1a vs. 1b) (P>0.05). Obtained PAF level in CSF after 36h, showed a profound decline in cooling group of infants compared to Group 1a infants (P<0.01). In conclusion, the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging. Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants.

Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2alpha and clinical parameters of chronic periodontitis.

BACKGROUND: The purpose of the present study was to evaluate the effect of a relatively selective cyclooxygenase (COX)-2 inhibitor (nimesulide) and non-selective COX-1/COX-2 inhibitor (naproxen) used as an adjunct to non-surgical (scaling and root planing [SRP]) periodontal therapy in chronic periodontitis patients on the gingival tissue (GT) levels of prostaglandin (PG)E2 and PGF2alpha. METHODS: Thirty patients with chronic periodontitis were divided into 3 groups of 10 each. One group received 100 mg of nimesulide; one received 275 mg of naproxen sodium; and the third group received placebo tablets in a 2 x 1 regimen for 10 days as an adjunct to SRP. GT samples were obtained before drug intake and on day 10. Plaque index (PI) and papillary bleeding index (PBI) scores were recorded at baseline, day 10, and at 3 months; probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and at 3 months. The levels of PGE2 were detected using an enzyme immunoassay (EIA), and the levels of PGF2alpha were analyzed by radioimmunoassay (RIA). Differences among and within the groups were assessed using non-parametric statistical analysis. Ten periodontally healthy individuals served as controls. RESULTS: All 3 groups showed statistically significant reductions in PBI and PI on day 10 and at 3 months (P < 0.02), and in PD and CAL at 3 months (P < 0.02, P < 0.05, respectively). In the naproxen group, GT PGE2 levels exhibited a significant decrease (P < 0.05). However, the decrease of GT PGE2 levels in the nimesulide group was insignificant (P > 0.05), while a significant increase was observed in the placebo group (P < 0.05) on day 10. Both the nimesulide and naproxen groups showed a significant decrease (P<0.05) in PGF2alpha level, while the placebo group showed a significant increase (P<0.05). CONCLUSIONS: Nimesulides, relatively selective COX-2 inhibitors, may have additional inhibitory effects on GT PGF2alpha levels in the first week following non-surgical periodontal treatment. However, nimesulide has an insignificant effect on reducing PGE2 levels in gingival tissue. The determination of GT levels of COX-1 and COX-2 enzymes as well as PGE2 and PGF2alpha in long-term studies may provide further support for the adjunctive use of selective COX-2 inhibitors in treatment of chronic periodontitis.

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. METHODS: Plasma FC concentrations were measured in age-matched 14 undialyzed patients, 20 dialyzed patients and 12 healthy children. In the HD group, measurements were done pre- and postdialysis and an hour after ceasing HD. None of the children have been receiving exogenous l-carnitine replacement. RESULTS: Plasma FC concentrations on either HD or conservative treatment were found to be decreased as compared to the healthy subjects (P < 0.001 and P = 0.001, respectively). The patients on HD had lower levels of plasma FC at the predialysis period than those on conservative treatment (P = 0.01). The FC levels significantly dropped at the postdialysis period as compared to those at the predialysis period (P < 0.001), but recovered at 1 h after ceasing HD. The mean duration of HD did not correlate with plasma FC levels at predialysis period. CONCLUSIONS: Children with CRF, either dialyzed or undialyzed, have decreased plasma FC levels. Hemo-dialysis treatment significantly depletes plasma FC concentrations during the procedure, but predialysis levels are reached 1 hr after ceasing HD.

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.