Plasma concentration of osteopontin [OPN] in children with systemic lupus erythematosus: relationship with disease activity

Osteopontin [OPN] is an important bone matrix mediator found to have key roles in inflammation and immunity. OPN is a cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between T-helper 1 and T-helper 2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Overexpression of OPN has been associated with the development of the autoimmune/lymphoproliferative syndrome. The aim of our present study was to analyze the possible correlation between the plasma concentration of OPN and disease activity in children with Systemic Lupus Erythematosus [SLE]. We also investigated the correlation between plasma IL-18 and OPN concentrations to further confirm the association of OPN with disease activity. We measured the plasma concentration of OPN, and the plasma proinflammatory IL-18 concentration in 40 SLE patients with or without renal disease [RSLE group and SLE group, respectively] and in 30 sex-and age-matched controls using enzyme immunoassay. Plasma OPN concentrations were significantly higher in RSLE and SLE patients than in the controls [p=0.000 and p=0.002]. Increase in OPN concentration correlated positively and significantly with SLE disease activity index in all SLE patients [r=0.34; p=0.04]. In RSLE patients, plasma OPN concentration showed a significant positive correlation with proinflammatory cytokine IL-18 concentration [r=0.48; p=0.004]. In conclusion, The above results suggest that the production of OPN is associated with the inflammatory process and SLE development, and may serve as a potential disease marker of SLE

Serum levels of ghrelin, tumor necrosis factor-A [TNF- A], and lnterleukin-6 [IL-6] in infants and children with congenital heart disease

Ghrelin increases food intake, body weight, and growth hormone secretion. The cause of growth retardation in congenital heart disease [CHD] is multifactorial. The aim of this study was to estimate serum levels of ghrelin, tumor necrosis factor-a [TNF-alpha], and interleukin-6 [IL-6] ih infants and children with CHD, compared with levels in age-matched controls, and to correlate the levels ofghrelin with TNF- alpha, and IL-6. We measured serum ghrelin, TNF- alpha and IL 6 levels using ELISA in 60 patients with CHD [40 acyanotic and 20 cyanotic] and in 20 control subjects. Our results showed that patients with CHD, whether compiled in one group or classified into acyanotic and cyanotic, had significantly higher serum ghrelin TNF- alpha, and IL-6 than controls [p = 0.000]. Serum levels of ghrelin and TNF- alpha in the acyanotic patients were significantly higher than in the cyanotic patients [p = 0.000]. On the other hand, there was no significant difference in serum levels of IL-6 between the acyanotic and the cyanotic patients [p = 0.126]. In acyanotic and cyanotic patients with CHD, there was a positive correlation between ghrelin and TNF- alpha [r = 0.424; p = 0.006 and r = 0.577; p = 0.008, resp.]. Ghrelin levels were not correlated with IL-6 in the acyanotic and cyanotic patients with CHD [r = -0.211; p = 0.216 and r = -0.341; p = 0.08, resp.]. Serum ghrelin, TNF- alpha, and IL-6 levels are elevated in patients with CHD whether acyanotic or cyanotic. Increased ghrelin levels represent malnutrition and growth retardation in these patients. The relation of ghrelin with TNF- alpha may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia

Plasma levels of adrenomedullin and total nitrite in infants and children with heart failure

Localization of adrenomedullin [ADM] in peripheral tissues, including the heart, kidney, and vasculature, suggests an important role for the peptide as a regulator of cardiovascular function. ADM has hemodynamic effects including vasodilation, increases in cardiac contractility cardiac output, diuresis, and natriuresis. These effects may incorporate many of the therapeutic goals of heart failure management. The aim of our study was to find a relation between plasma level of ADM and Nitric Oxide [NO] in heat failure, with special interests to the type of heart disease, age, sex of patients, and severity of heart failure. We compared plasma levels of ADM and Nitric oxide [NO] in three groups of patients with heart failure: 14 patients diagnosed as rheumatic heart disease [RHD] [group I], 10 patients diagnosed as congenital heart disease [CHD] [group II], 6 patients diagnosed as dilated cardiomyopathy [DCM] [group III] and 20 apparently healthy children who were taken as controls [group IV]. Patients with heart failure had significantly higher levels of ADM and NO than controls [p=0.0001]. ADM and NO were highest among the patients with heart failure due to RHD then congenital heart disease and lastly dilated cardiomyopathy respectively [P=0.02 and 0.04 respectively]. We concluded that ADM is a biochemical marker for evaluating the severity of heart failure, and may be a new and promising approach for the treatment of patients with heart failure and pulmonary hypertension in children. In the future, insights into the role of NO in cardiac remodeling should allow the development of novel therapeutic strategies to treat cardiac remodeling and failure in infants and children

Serum troponin in neonates of pre-eclamptic mothers

Cardiac troponin I, the biochemical marker of myocardial injury is characterized by high sensitivity and specificity in comparison with other markers used in the past. The aim of this study was to evaluate serum levels of troponin in neonates of pre-eclamptic mothers compared with levels in age and sex matched controls, and to correlate the levels of troponin I with Cardiac Creatine Kinase [CK-MB] and other markers of myocardial injury. Forty neonates of pre-eclamptic mothers were included in the study [group A]. Also, 30 age and sex matched healthy neonates were included as controls [group B]. All neonates were subjected to full clinical assessment and routine laboratory investigations. Echocardiographic study was done stressing on myocardial contractility, and calculating the E/A ratio where E= Mitral peak velocity of early diastole in centimeters per second, and A Peak velocity of the atrial contraction in centimeters per second. Cardiac troponin [was measured in serum by ELIZA. CK-MB was measured in serum by chemical analysis. The results showed that troponin I, CK-MB, and E/A levels were significantly higher in group A compared with group B [p=0.003, p=0.03, and p=0.01 respectively]. There were significant positive correlations between troponin I with CK-MB, C-reactive protein and the mean E/A value in group A [r=0.86; p=0.02, r=0.50; p=0.01, and r=0.75; p=0.05 respectively]. Troponin I had a sensitivity of 83.3% and a sensitivity of 86.6% in diagnosing myocardial injury while CK-MB had a sensitivity of 75% and a specificity of 76% in diagnosing myocardial injury. From the present study we conclude that cardiac Troponin I is a more specific and more sensitive marker for myocardial injury than the standard biochemical markers such as CK-MB and it can detect minor myocardial damage not diagnosed early by echo cardio graphic study. Also we conclude that preterm neonates of preeclamptic mothers are more susceptible to myocardial injury than full-term neonates. Troponin I may have prognostic significance because, if present, it identifies the neonates of pre-eclamptic mothers who are at risk of cardiac injury

Interleukin-18 and nitric oxide and gene expression of IL-18 in children with lupus nephritis

Autoimmune diseases might be caused by an imbalance of T-helper cell [Th] cytokines. Lupus nephritis [LN] is dominated by a Th1 immune response in systemic lupus erythematosus [SLE]. Interleukin-18 [IL-18] promotes polarization of the immune response towards Th1 in LN. Nitric oxide [NO] is involved in the pathogenesis of glomerulonephuitis and collagen-vascular diseases. The aim of the present study is to investigate role of IL-18 and NO in patients with LN and to study the correlation between them and Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] score and whether these two molecules are associated with renal involvement in patients with SLE. We investigated plasma concentrations of IL-18 and NO and gene expression of IL-18 was analyzed by Reverse transcription-polymerase chain reaction [RT-PCR] in 19 SLE patients with LN, [group1] and 15 SLE patients without renal involvement [group2] and 15 age- and sex-matched healthy control subjects [group3]. IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Plasma IL-18 and NO concentrations were significantly higher in renal group 1 than non renal group 2 and normal control group 3 [p=0.001 and 0.01 respectively]. Elevation of plasma IL-18 in renal group 1 correlated positively with SLE disease activity index and plasma NO concentration [r=0.35, p=0.0001 and r= 0.46, P=0.01, respectively], and the latter also showed a positive correlation with serum creatinine [r=0.69, P=0.001] and urea [r = 0.28, P = 0.001]. There was no significant difference in gene expressions of IL-18 in peripheral blood mononuclear cells among renal group 1, non renal group 2 and normal control group3. IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE. IL-18 may play a crucial role in the inflammatory process of renal disease in SLE and its measurement may be helpful for the early identification of lupus patients with LN. Elevated concentrations of circulating NO can serve as indicators of endothelial activation and/or damage, which may occur in the pathogenesis of SLE with LN

Serum levels of ghrelin in healthy children and in children with simple obesity and the effect of insulin and glucose on ghrelin secretion

In addition to its regulation by GH releasing hormone [GHRH] and somatostatin, release of GM from the pituitary is modulated by a third factor, ghrelin, which is expressed in high concentration in the stomach and is present in the circulation. Ghrelin has also been shown to cause weight gain by increasing food Intake and decreasing fat utilization. Ghrelin is a potential candidate hormone to influence nutrient intake and growth. Its role through normal childhood and adolescence has not been fully defined. Ghrelin levels increase before and decrease after meals, potentially playing a role in meal initiation and satiety in an inverse pattern to that of insulin. The role of ghrelin in childhood obesity a state associated with hyperinsulinism and insulin resistance, is not fully understood. Therefore, the aims of the present study were to Investigate the dynamics of ghrelin suppression after an oral glucose tolerance test [OGTT] in normal weight [NW] children versus children with simple obesity [SO] and the relationship of ghrelin suppression to insulin sensitivity. Fifteen NW [8 males and 7 females] and 15 children with SO [8 males and 7 females] prepubertal children from 8-12 years underwent a 3-h OGTT with measurements of ghrelin, glucose, and Insulin at 0, 30 and 60 minutes. The fasting glucose to insulin ratio and the whole body insulin sensitivity index were used to assess the relationship of insulin sensitivity to tasting ghrelin and ghrelin response to the OGTT respectively. Fasting ghrelin levels were significantly lower in children with SO versus NW children and were mainly influenced by insulin sensitivity. OGTT-induced suppression in ghrelin which was less in children with SO versus NW children, resulting in a similar suppression from baseline in the two groups despite a significantly higher insulin response in children with SO. The suppression of ghrelin correlated positively with the whole body insulin sensitivity index [r= 0.43; P = 0.001] and negatively with the change in insulin at 30 min [r = -0.31; P = 0.02]. Fasting ghrelin and ghrelin suppression after OGTT are modulated by insulin sensitivity. Alterations in ghrelin suppression in SO children may be yet another manifestation of the insulin resistance of obesity. Whether this is responsible for differences in satiety in obese individuals merits additional investigation

Plasma interleukin-11 levels in thrombocytopenic and non-thrombocytopenic neonates

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. The thrombopoietic cytokine recombinant human IL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, little is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis [NEC] with or without thrombocytopenia. At birth IL-11 was undertetable [<10pg/ml] in healthy term neonates [n = 15] and 21 of 25 [84%] stable preterm neonates. Three stable preterm neonates had detectable plasma IL-11[mean, 11.23 +/- 0.64 pg/ml], all three were born after pregnancies complicated by prolonged rupture of membranes or chorioamnionitis, the remaining neonate[IL-11, 15 pg/ml] being one of seven with early onset thrombocytopenia [presented by 72 h of age]. IL-11 was also measured in 50 preterm neonates with suspected sepsis or NEC. In 20 of 50, sepsis or NEC was unconfirmed and IL-11 was undetectable, in contrast, 14 of 30 with proven sepsis or NEC had elevated IL-11 [mean, 25.41 +/- 21.3; range, 11.3-93 pg/ml] [p = 0.0003]. Of the 30 neonates with proven sepsis or NEC, 19 developed thrombocytopenia: nine of 19 [47.4%] had detectable IL-11 and 10 of 19 [52.6%] did not [p = 0.746]. Although the role of IL-11 in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response

Brain-derived neurotrophic factor [BDNF], and neurotrophin 3 [NT3] levels in newborn cord sera

During embryonal development, neuronal death occurs only by apoptosis and not by necrosis. Apoptotic neuronal loss may be responsible for altered brain development associated with prematurity and perinatal insults. Neurotrophic factors such as brian-derived neurotrophic factor [BDNF], and neurotrophin 3 [NT3] play crucial roles in protecting neurons form entering or progressing along an apoptotic pathway. The aim of this work was to measure BDNF and NT3 level at different gestational ages in human umbilical cord blood. In addition, we searched for differences in BDNF and NT3 levels in the presence or absence of factors that may affect intrauterine conditions and thus neurodevelopmental outcome. We collected 80 samples of cord blood and categorized them accordingly into three gestational age groups: group 1 [24-30 weeks], group 2 [31-36 weeks], and group 3 [37-42 weeks]. BDNF and NT3 levels were determined by ELISA. The BDNF levels were 798.3 +/- 492.5, 1401 +/- 650.8, and 2236.6 +/- 376.8 pg/ml in group 1, group 2, and group 3, respectively, with a significant difference between the 3 groups [p=0.0001]. In contrast, NT3 levels did not show significant change across gestational ages [p=0.2]. NT3 levels also did not correlate with BDNF levels across gestational ages [r=0.23; p=0.27]. The presence of premature rupture of membranes, chorioamnionitis, pregnancy-induced hypertension, or small for gestational age did not alter either BDNF or NT3 levels significantly. BDNF and NT3 levels were significantly higher in samples from subjects whose mothers received two doses of antenatal steroids compared with those who received only one dose of steroids, and those with no antenatal steroids[p=0.001, and p=0.04]. Cord blood levels of BDNF may reflect the degree of neutral maturity in premature infants. Increased BDNF and NT3 levels may also mediate improved neurodevelopment outcome in infants who received antenatal steroids

Usefulness of serum procalcitonin and urinary interleukin-8 in pediatric urinary tract infection

This work studied 40 infants and children [14 males and 26 females] with manifestation suggestive of urinary track infection [UTI], their ages ranged from 6 months to 8 years, in addition to 40 apparently healthy children of matched age and sex, as a control group. Serum PCT, urinary IL-8, C-reactive protein [CRP] and total leukocytic were measured in all patients and controls. In cases with positive urine culture, renal parenchymal involvement was assessed by 99TcDMSA renal scan in the first five days after admission. From the results obtained, it was concluded that in infants and children with suspected UTI, serum PCT and urinary IL-8 may be used as markers of infection, their levels vary with the severity of infection and were increased significantly when renal parenchymal involvement is present. Taking the appropriate clinical situations into account, their measurement might be a useful and practical tool for differentiating acute pyelonephritis from lower UTI