Urinary creatinine and serum cystatin C in asthmatic children treated with inhaled corticosteroid and beta 2 agonist

L-arginine, an amino acid involved in the production of urea, creatinine and nitric oxide [NO] that is known to play an important role as an inflammatory mediator in the airways. Inhaled corticosteroids and beta [2] agonists are the most frequently prescribed medications in the management of chronic asthma. Current guidelines emphasis their complementary role. Although many patients use both drugs, there is little information on the effectiveness of their combination. In the present study we investigated the effect of a combination of glucocorticoids and beta [2] -agonists inhaled by asthmatics on the metabolism of L-arginine. Sixty-six children with mild-to moderate asthma were enrolled in this study and treated with different regimens of inhaled drugs but fifty three children only completed the study [Twenty one with inhaled beta [2] agonist [salmeterol], 15 with inhaled corticosteroid [fluticasone propionate], and 17 with a combination of inhaled salmeterol and fluticasone propionate]. Fifteen healthy-matched children served as a control group. Pulmonary function tests [forced expiratory volume in one second [FEV[1]], peak expiratory flow rate [PEFR]], methacholine challenge tests, serum cystatin C, 24 hours urinary measurement of urea, creatinine, nitrates, and urinary osmolality were performed before and after three months of the inhaled drug therapy. The results of this study demonstrated: [1] Non significant differences in serum cystatin C and urinary urea, creatinine, nitrates, osmolality were noted in asthmatic children vs control group. [2] non significant differences in serum cystatin C level and urine osmolality were observed in different groups before and after therapy. [3] compared to that before therapy, children treated by the combination of corticosteroid and beta [2] agonist had a significant higher level of urinary creatinine [p=0.0001] and a higher creatinine/urea ratio [c/u ratio] [p=0.0001] with significantly lower levels of urinary urea [p=0.002], and urinary nitrates [p=0.0001]. [4] in children treated by the combination of corticosteroid and beta [2] -agonist, there were a significant positive correlations between urinary creatinine and both FEV[1] [r= +0.699, p<0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [R= +0.695, P< 0.01]. Also there were significant positive correlations between c/u ratio and both FEV[1] [r= +0.821, p = <0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [r= +0.850, p< 0.01]. [5] in children treated with corticosteroid alone, only urinary nitrates was significantly lower after treatment as compared to that before treatment. [6] in children treated with beta [2] agonist alone, no significant differences in urinary urea, creatinine, nitrates and c/u ratio as compared to that before therapy. In asthmatic children, treatment with a combination of inhaled corticosteroid and beta [2] -agonist had a beneficial augmenting influence on the metabolism of L-arginine with better improvement of lung functions and bronchial hyperreactivity than treatment with either corticosteroid or beta [2] -agonist alone. Also creatininuria and urinary c/u ratio can be used as a simple and noninvasive parameters for assessment of response to treatment in these children. Also our results demonstrated normal serum cystatin C concentrations in asthmatic children in between attacks and remained unaffected by a therapy with inhaled corticosteroid, beta [2] agonist or a combination of both

Plasma adrenomedullin and brain natriuretic peptide in children with chronic congestive heart failure

The goal of this study is to delineate the role of adrenomedullin [ADM] and brain natriuretic peptide in the pathophysiology of chronic heart failure [CHF] and the potential use of their circulating levels for diagnosis and treatment of heart failure. Fifty children [19 males and 31 females] with chronic congestive heart failure [CHF] were enrolled in this study. Plasma ADM and BNP levels were assayed by radioimmunoassay and ELISA respectively. Enrolled children were classified into four classes according to New York association functional class [NYHA]. Their age ranged between one year to fifteen years. Twenty-one children [8 males and 13 females] with age ranging from 3-13 years served as control group. The results showed that the plasma concentrations of adrenomedullin [ADM] in pg/ml increased progressively with advancing class of heart failure by NYHA; 3.45 +/- 0.59 for class I, 5.32 +/- 0.95 for class II, 7.29 +/- 1.18 for class III and 14.65 +/- 2.06 for class IV, that were significantly higher than in controls [1.97 +/- 0.46, P<0.001]. Also, plasma BNP concentrations in ng/l were 42.56 +/- 4.14, 129.4 +/- 18.85, 569.05 +/- 37.76 and 1039 +/- 359.57 respectively in children of NYHA class I, II, III and IV, that were higher than in controls [9.21 +/- 1.433, P<0.001]. there was a significant positive correlation, between ADM and BNP in relation to severity of heart failure. ADM and BNP concentrations were significantly reduced after treatment. Adrenomedullin and natriuetic peptide appears to participate actively in the pathogenesis and perpetuation of chronic heart failure in children. This fact might open a new pathogenesis and perpetuation of chronic heart failure in children. This fact might open a new therapeutic channel for children with heart failure to prevent progression to chronicity and to those with already chronic heart failure through uses of ADM and BNP agonist specific for their receptors

Evaluation of endothelin-1 and Von Willebrand factor as biomarkers of pulmonary hypertension in children with congenital heart disease

This study was done to delineate the role of endothelin-1 [ET-1] and von willebrand factor [vWF] in the pathophysiology of pulmonary hypertension [PHT] secondary to congenital heart disease. Forty-three children [29 males, 14 females] with cyanotic and acyanotic congenital heart diseases were enrolled in this study. Their age ranged between 4 months 5.10 year. Plasma ET-1 levels and vWF:Ag activity were assayed by enzyme linked immunosorbent assay. Enrolled children were divided into three groups according to pulmonary artery pressure [PAP]. Group 1 with normal PAP [/= 50mmHg] [n=14]. Twelve perfectly matched healthy children were enrolled as a control group. The results of the present study showed that plasma ET-1 levels in group I were significantly higher than that in control group [P<0.001], on the other hand no significant differences were noted in vWF: Ag% in both groups. Plasma endothelin-1 and vWF:Ag were significantly elevatd in all groups with PHT Vs controls [P<0.001 and P<0.001]. Plasma endothelin-1 and vWF: Ag% were significantly elevated in group III Vs both group II and I [P<0.001]. plasma endothelin-1 and vWF:Ag% were significantly elevated in group II Vs group I [P<0.001 and P<0.001]. Plasma ET-1 levels and vWF:Ag% positively correlated with pulmonary artery pressure in group II and III [P<0.001 and P0.001]. Elevated ET-1 and vWF may contribute directly to development of pulmonary hypertension in children with congenital heart diseases. ET-1 and vWF estimation could be used as non-invasive early markers of pulmonary hypertension in such children, particularly in post-operative evaluation. Our data are in keeping with evidence of significant coagulation abnormalities in pulmonary hypertension and the need for chronic anticoagulant therapy may increase survival in children with pH. These facts opened the door for exploring therapeutic anti-ET-1 and anti- vWF agents in the treatment of pulmonary hypertension in children

Plasma levels of soluble CD14 and endothelin-1 in infants with respiratory syncytial virus-induced bronchiolitis as predictors of subsequent recurrent wheezing in a two years follow-up study

Respiratory syncytial virus [RSV] infections have been demonstrated to be associated with subsequent recurrent wheezing episodes and the development of childhood asthma. The CD14 receptor responds to the microbial burden in the environment and modulates the development of the allergic phenotype. Endothelin-1 is a potent bronchoconstrictor involved in many diseases including respiratory tract infections. Plasma levels of soluble CD14 [SCD14] and endothelin-1 [ET-1] were measured by a commercially available enzyme-linked immunosorbent assay [ELISA] in 32 infants who were hospitalized with RSV bronchiolitis to investigate their relation to the subsequent development of recurrent wheezing during a two years follow-up period. Thirty healthy infants were served as a control group. The results proved that the mean level of plasma sCD14 was significantly lower in infants with acute RSV bronchiolitis compared to control group [22.01 +/- 6.27 vs 817.50 +/- 247.52 ng/ml, p<0.001]. The mean sCD14 plasma level of 18.52 +/- 5.24 ng/ml in the group of 19 children who exhibited recurrent wheezing was significantly lower than the level of 27.11 +/- 3.57ng/ml in the group of 13 children who did not exhibit recurrent wheezing [P<0.001]. the mean plasma level of ET-1 was significantly increased in infants with RSV bronchiolitis compared to the controls [3.86 +/- 1.44 vs 0.71 +/- 0.18 pg/ml, p<0.001] and the mean plasma ET-1 level of 4.60 +/- 1.17 pg/ml in the group of children who exhibited recurrent wheezing was significantly higher than level of 2.78 +/- 1.11 pg/ml in the group of children who did not exhibit recurrent wheezing [P<0.001]. the risk for subsequent development of recurrent wheezing was not influenced by age at hospitalization, sex, breast-feeding, positive family history of atopy, or passive smoking. The results of this study showed that plasma level of sCD14 was decreased and plasma endothelin-1 was increased in infants during acute RSV bronchiolitis and their levels were significantly different in infants who had experienced subsequent wheezing than in infants who not and that reduced plasma sCD14 and increased ET-1 levels in infants with RSV bronchiolitis are useful in predicting the risk to develop subsequent recurrent wheezing. From the results of this study, it can be recommended that CD14 may be a potential target for preventive measures against atopic diseases. This study also encourage further studies on the value of ET-1 antagonism among alternative therapeutic modalities of childhood asthma

Elevated plasma matrix metalloproteinase-9 level in hepatocellular carcinoma: is it induced by hepatocyte growth factor?

Hepatocellular carcinoma [HCC] is one of the most common cancers worldwide affecting one million cases per year. The aim of the present study was to evaluate the diagnostic role of plasma matrix metalloproteinase-9 [MMP-9] in patients with HCC and its relation to hepatocyte growth factor [HGF]. This study was conducted on 30 patients classified into: Group II included 10 patients with chronic active hepatitis. Group III included 10 patients with liver cirrhosis and Group IV included 10 patients with HCC. Ten healthy subjects were also included in the study as a control group [group I]. Alt studied groups were subjected to clinical, laboratory, ultrasonographic examination and estimation of serum alpha-fetoprotein [APP], HGF and plasma MMP-9. There were significant elevations in serum levels of AFP. HGF and plasma levels of MMP-9 in patients with HCC compared to other studied groups. Also serum AFP and HGF levels in group II and III were higher than those of the controls. However, MMP-9 levels in group II and III were not significantly different from those of the controls. Also MMP-9 and HGF levels were significantly higher in HCC patients with lung metastasis. portal invasion and tumour size

effect of metformin on the endocrine variables in clomiphene resistant polycystic ovarian disease

To investigate the effect of metformin on the endocrine variables in clomiphene resistant polycystic ovarian disease [PCOD]. Departments of Obstetrics and Gynaecology, Internal Medicine and Clinical Pathology, Faculty of Medicine, Tanta University, Egypt. Thirty-three infertile women due to PCOD were enrolled and divided into 23 cases received oral metformin 850 ma/ twice daily for 8 weeks and 10 cases received placebo for the same period. Basic hormonal parameters, serum glucose and insulin were tested before and after treatment. Metformin led to 65% improvement in acne score, 57% menstrual improvement and significant reduction of serum LH androstenedione, DHEAS, free testosterone, glucose and insulin. Highly significant elevation of SHBG was observed. The mean fasting insulin dropped from 28 uU/ml before to 16 uU/ml after therapy and this drop was significantly correlated to changes in testosterone, free testosterone, SHBG and glucose. Metformin may be suggested as a therapy for women with colomiphene resistant polycystic ovarian disease. It can ameliorate hyperinsulinemia, hyperadrogenemia with their impacton the restoration of regular menses and ovulation; and hence improving the pregnancy capability

Cardiac troponin-T as a diagnostic marker in children with rheumatic carditis

Rheumatic carditis is the most serious major manifestation of acute rheumatic fever in children. Cardiac Troponin-T [cTnT] is established as a new specific marker of myocardial damage or injury. The present work was carried out to study the value of cTnT as a diagnostic marker of myocardial injury in children with rheumatic carditis, and to compare it to established parameters of myocardial injury such as creatine kinase [CK] and its MB isoenzyme. Forty-five children with acute rheumatic fever were enrolled in the study; classified into 3 groups: group [A]: 15 children with rheumatic carditis without cardiomegaly, group [B]: 15 children with rheumatic carditis and cardiomegaly and group [C]: 15 children with other rheumatic presentations. Fifteen normal healthy children were enrolled as a control group. All children included in the study were subjected to diagnostic laboratory and radiological investigations, including serum total CK, CK-MB isoenzyme% [using electrophoresis] and cTnT [by immunoassay test]. Our results showed significant elevation of cTnT, total CK and CK-MB isoenzyme in children with rheumatic carditis [groups A and B], as compared to the control group [P < 0.05]. These values were significantly higher in group [B] children [with cardiomegaly], as compared to group [A] children [P<0.05]. Also, the ideal cut-off point for cTnT was found to be 0.1 micro g/L with a sensitivity 100%, while the sensitivity for CK-MB was 86.7% and that for total CK was 53.3%.we conclude that cardiac troponin-T [cTnT] can be used as a diagnostic marker of myocardial injury in children with rheumatic carditis, with a higher sensitivity than CK and its MB isoenzyme

Serum intercellular adhesion molecule-1 and leukotreine B4 in children with bronchial asthma: correlation with bronchial hyperreactivity

The objective of the present study was to investigate circulating intercellular adhesion molecule-1 [cICAM-1] and serum Leukotreine B[4] [LTB[4]] in asthmatic children. Twenty five asthmatic children and similar number controls were enrolled. Using enzyme immunoassay techniques, serum ICAM-1 and LTB[4] levels were determined on admission in acute attacks, 24 hrs and 2 weeks after remission. Bronchial hyperreactivity was tested in 10 patients with forced expiratory volume in one second [FEV[1]]> 80% using Methacholine inhalation provocation test. The results of the present study showed that cICAM-1 and LTB[4] increased significantly in patients with acute attacks Vs controls [P<0.05]. Both cICAM-1 and LTB[4] levels correlated significantly with severity as well as frequency of acute attacks [P<0.05], but correlated insignificantly with the atopic status of the patients as well as bronchial hyperreactivity represented by the peak concentration of methacholine at which FEV[1] dropped by 20% of post-saline inhalation value[PC20FEV1] [P>0.05]. Serum ICAM-1 and LTB[4] showed insignificant drop 24 hr after remission [P>0.05]. But significantly dropped two weeks later on [P < 0.05]. Those patients with chronic asthma sustained significantly higher levels of cICAM-1 and LTB[4] two weeks after remission [P<0.05 Vs controls]. There was significant drop in LTB[4] 24hr after remission in dexamethazone-treated patients Vs non-dexamethazone treated patients [P<0.05]. cICAM-1 levels showed no such significant drop [P>0.05]. However, dexamethazone administered during acute paroxysm showed insignificant effect on cICAM-1 and LTB[4] levels obtained two weeks after remission [P>0.05]. In conclusions i]. The present data suggested that ICAM-1 and LTB[4] may play a remarkable pathophysiologic role in acute and chronic asthma in children. ii] ICAM-1 and LTB[4] are suggested to have no influence on bronchial hyperreactivity in asthmatic children and both are not influenced by the atopic status of the child, but closely linked to the severity and frequency of acute asthmatic attacks and chronicity of asthma iii] cICAM-1 is under limited steroid control, while LTB[4] levels is suggested to be steroid-sensitive iv] The present data, opens the door in the near future, for possible therapuetic interventions using novel anti-inflammatory agents acting by blocking ICAM-1 molecules and LTB[4] receptors, in acute and chronic asthma in children