Serum ghrelin levels in children with celiac disease

OBJECTIVES: Ghrelin, a gastrointestinal hormone, has effects on nutrient intake and growth. Because celiac disease (CD) has intestinal histopathologic alterations and subsequent malnutrition and/or growth failure, we hypothesized that there would be alterations in serum ghrelin levels of those patients. In this study, we aimed to determine serum ghrelin levels in childhood CD, to observe probable alterations under gluten-free diet (GFD), and to see whether there is a relationship between ghrelin levels and the presentation of the disease and/or diet compliance. METHODS: Thirty-six children with CD and 10 healthy children were included. Serum fasting ghrelin level was measured using radioimmunoassay method. After 6 months under GFD, sera of 19 patients were retested for ghrelin level. RESULTS: Mean serum ghrelin levels in children with CD and in controls were 478.2+/-154.6 and 108.3+/-49.1 pg/mL, respectively (P<0.001). Serum ghrelin level was not different in different clinical presentations. Ghrelin was negatively correlated with body mass index, both in healthy children and in children with CD on admission (P<0.01). Ghrelin level was lower after 6 months under GFDcompared with the level detected on admission (P<0.001), but was still higher compared with that of healthy children (P<0.001). Strict diet compliance lowered ghrelin level, although not statistically. CONCLUSIONS: Ghrelin is increased in childhood CD and is responsive to GFD. Further studies are needed to clarify the mechanism underlying its action in CD.     

Serum leptin levels in childhood celiac disease

OBJECTIVE: Leptin has effects on growth and is also involved in immune regulation. We thought that with its intestinal histopathologic alterations due to immune mechanisms, and subsequent malnutrition and/or growth failure, celiac disease (CD) deserves interest regarding leptin status. METHOD: Serum leptin levels of 19 children with CD on admission and 1 year after gluten-free diet (GFD) and of 16 healthy children were determined. RESULTS: Mean age was 9.7+/-3.3 years. Mean serum leptin level of children with CD on admission and of healthy children were 1.60+/-0.63 ng/mL, and 3.98+/-1.49 ng/mL, respectively (P: 0.0001). Mean serum leptin level under GFD was 4.55+/-1.97 ng/mL. There was a statistical significant difference between serum levels determined before and 1 year after GFD (P: 0.001) and between those of under GFD and healthy children (P: 0.001). Of 19 patients with CD, 10 (52.6%) showed Marsh IIIc, other 9 (47.4%) showed Marsh IIIa histologic lesions. Mean serum leptin level of children with Marsh IIIc and Marsh IIIa were not different (1.70+/-0.73 ng/mL vs. 1.45+/-0.59 ng/mL). Leptin was correlated with body mass index in healthy children, and in CD both before and after GFD (P<0.001). Mean lumbar z score of the patients on admission and after GFD were 2.7+/-1.3 and 1.9+/-0.8, respectively (P: 0.048). Serum leptin level was not correlated with lumbar z score either before or after GFD. CONCLUSIONS: Serum leptin level is affected in childhood CD, it is not directly related to histopathologic findings, and is responsive to GFD. Further studies investigating its level in different clinical and histopathologic presentations might give clear clues about the role of leptin in CD.     

川崎病患儿血清瘦素一氧化氮白细胞介素-6的变化

目的 探讨川崎病(KD)患儿血清瘦素、一氧化氮(NO)、白细胞介素(IL)-6含量变化规律及其临床意义.方法 动态测定45例[冠状动脉损害(CA)12例和非冠状动脉损害(NCA)33例]KD急性期及其缓解期患儿及30名健康儿童血清瘦素、NO、IL-6、C反应蛋白(CRP)含量变化并分析它们的相关性.同时测定18例其他结缔组织疾病组(其中幼年特发性关节炎6例,过敏性紫癜12例)儿童血清瘦素水平.血清瘦素、NO及IL-6浓度的测定分别采用放射免疫方法、硝酸还原酶法及酶联免疫吸附方法.结果 ①KD急性期血清瘦素、NO、IL-6、CRP浓度高于KD缓解期及正常对照组.差异有统计学意义(q值分别为26.24、25.23;21.38、31.30;35.37、33.68;16.32、15.66;P均＜0.01);KD缓解期血清瘦素、IL-6、CRP浓度下降,较对照组差异无统计学意义(q值分别为1.02、1.04、0.61,P均＞0.05);KD缓解期血清NO有下降,较对照组差异仍有统计学意义(q值为11.31,P＜0.01).②与NCA组比较,CA组血清瘦素、IL-6、CRP浓度差异无统计学意义(q=1.17、1.92、3.08、1.60,P均＞0.05);NO差异有统计学意义(g=6.91,P＜0.01).③其他结缔组织疾病组(18例)患儿血清瘦素水平为(13.3±4.2)μg/L,与正常对照组(30例)血清瘦素(2.6cc0.8)μg/L比较,差异有统计学意义(t=13.26,P＜0.01);与KD急性期(45例)血清瘦素(14.7±3.8)μg/L比较,差异无统计学意义(t=1.28,P＞0.05).④KD患儿急性期血清瘦素与NO、IL-6、CRP呈正相关(r值分别为0.69、0.55、0.42,P值均＜0.01);但KD患儿急性期血清瘦素与白细胞计数、白蛋白浓度无相关性(r值分别为0.21、-0.24,P值均＞0.05);KD患儿急性期血清NO与IL-6、CRP浓度呈正相关(r值分别为0.45、0.49,P值均＜0.01).结论 瘦素、NO、IL-6参与KD患儿免疫炎症过程.     

Measurement of expired nitric oxide levels in children

Nitric oxide (NO) can be measured directly in expired air in adults. The purpose of our study was to measure NO levels in children and to compare these values with adults. Exhaled NO was measured in 39 normal prepubertal children (23 girls), aged 9–11 years (mean, 9.9 years). Exhaled NO was measured by the chemiluminescence method that is sensitive in a range of 2 to 4,000 ppb of NO on an adapted analyzer (Dasibi Environmental). Wearing a nose clip, 5 measurements were recorded in each child with exhalation 1) directly into the NO analyzer (flow rate 240 mL/min) with measurements of NO, carbon dioxide, and mouth pressure; and 2) using a T-piece to allow measurements at a different flow rate. For all measurements, background NO levels were less than 10 ppb. The mean direct level was 49.6 ppb, SD 37.8 (range, 11.5–197.2 ppb) compared with T-piece levels of 29.2 ppb, SD 27.1 (range, 5.1–141.2 ppb). There was no significant difference between boys and girls for direct or T-piece recordings. Mean direct NO in boys was 43.1 ppb, SD 40.5 and in girls 55.2 ppb, SD 35.4, mean T-piece in boys was 25.6 ppb, SD 29.2, and in girls 33.8 ppb, SD 25.1. Mean NO levels in prepubertal children are lower than in adults and show no difference between males and females. Pediatr Pulmonol. 1996; 22:396–401. © 1996 Wiley-Liss, Inc     

Cirrhosis in children with celiac disease

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.     

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO _x (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO _x was measured by chemiluminescence. Serum NO _x levels in SSc (n = 43) were significantly higher (72.4 ± 47.8 μM) than age- and sex-matched controls (n = 41; 37.1 ± 13.5 μM; p < 0.001). Serum NO _x were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO _x level defined as mean ± 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO _x . Prednisolone use was associated with lower serum NO _x level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO _x (p = 0.004 by trend). Serum NO _x in SSc patients were elevated compared to healthy controls. Serum NO _x level was determined by multiple factors including age, prednisolone use, and elevated PAP.     

Serum antibodies in celiac disease

Accurate diagnosis of celiac disease is important because patients are advised to adhere to a strict gluten-free diet for life. This management is critical to avoid disease complications such as malignancies. In this review the new terminology for the disease clinical features (active, silent, latent and potential celiac disease) and the disease association with other conditions are commented. The value and efficacy of the assessment of serum antigliadin antibodies and of antireticulin, antiendomysial and tissue transglutaminase autoantibodies in the diagnosis and follow-up of the celiac disease are particularly evaluated.     

Enteric glial-derived S100B protein stimulates nitric oxide production in celiac disease

BACKGROUND & AIMS: Enteric glia participates to the homeostasis of the gastrointestinal tract. In the central nervous system, increased expression of astroglial-derived S100B protein has been associated with the onset and maintaining of inflammation. The role of enteric glial-derived S100B protein in gastrointestinal inflammation has never been investigated in humans. In this study, we evaluated the expression of S100B and its relationship with nitric oxide production in celiac disease. METHODS: Duodenal biopsy specimens from untreated and on gluten-free diet patients with celiac disease and controls were respectively processed for S100B and inducible nitric oxide synthase (iNOS) protein expression and nitrite production. To evaluate the direct involvement of S100B in the inflammation, control biopsy specimens were exposed to exogenous S100B, and iNOS protein expression and nitrite production were measured. We also tested gliadin induction of S100B-dependent inflammation in cultured biopsy specimens deriving from on gluten-free diet patients in the absence or presence of the specific S100B antibody. RESULTS: S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production were significantly increased in untreated patients but not in on gluten-free diet patients vs controls. Addition of S100B to control biopsy specimens resulted in a significant increase of iNOS protein expression and nitrite production. In celiac disease patients but not in controls biopsy specimens, gliadin challenge significantly increased S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production, but these effects were completely inhibited by S100B antibody. CONCLUSIONS: Enteric glial-derived S100B is increased in the duodenum of patients with celiac disease and plays a role in nitric oxide production.     

Eosinophilic esophagitis in children with celiac disease

Background and Aims:  Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients.
Methods:  The medical records of patients diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed. Patients with coincident histological diagnosis of eosinophilic esophagitis were retrospectively identified. The presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, and treatment and follow-up outcomes of these patients were analyzed.
Results:  Of the 221 patients with celiac disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A majority (6/7) presented with periumbilical pain and diarrhea. None had dysphagia. Each patient had abnormal celiac screening tests. Three patients had peripheral blood eosinophilia and elevated eosinophil cationic protein. Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent in the majority of patients (6/7). A gluten-free diet was instituted in every patient. Topical corticosteroid therapy was started in one patient at diagnosis and in another patient after repeat endoscopic and histopathological evaluations.
Conclusions:  Awareness of the potential coexistence of eosinophilic esophagitis and celiac disease should promote optimal diagnosis of these conditions. Routine esophageal biopsies may be warranted when investigating for celiac disease.     

Raised exhaled nitric oxide in healthy children is associated with domestic formaldehyde levels

Exposure to domestic levels of formaldehyde has been associated with adverse respiratory symptoms in both adults and children. The underlying mechanisms responsible for these findings have not been established. In order to investigate possible inflammatory effects of formaldehyde at levels typically found in the home, we measured exhaled nitric oxide (eNO) in 224 healthy children 6 to 13 yr of age (116 girls) and monitored formaldehyde levels in their homes. Formaldehyde was monitored using a passive sampling technique. Exhaled NO was measured directly into a fast response chemiluminescence nitric oxide analyzer. The children also undertook a lung function (spirometry) test. There was no effect of formaldehyde levels measured in homes on spirometric variables. However, eNO levels were significantly elevated in children living in homes with average formaldehyde levels >/= 50 ppb. Exhaled NO levels (geometric mean) were 15.5 ppb (95% CI: 10.5 to 22.9 ppb) for children from homes with formaldehyde concentrations >/= 50 ppb compared with 8.7 ppb (7.9 to 9.6) for children from homes with formaldehyde concentrations < 50 ppb (p < 0.05). These results suggest that exposure to formaldehyde in homes may invoke a subclinical inflammatory response in the airways of healthy children.     

Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study

We proposed to assess antioxidant status and nitric oxide in fibromyalgia (FM) patients in comparison to healthy controls. Additionally, the association between the serum antioxidant levels and clinical findings in FM patients was also investigated. Thirty-seven FM patients and 37 healthy controls were enrolled in this study. Severity of fatigue and pain were determined by Visual Analogue Scale. Functional capacity in daily living activities was evaluated by fibromyalgia impact questionnaire. Serum NO, catalase and glutathione were measured. Serum glutathione and catalase levels were significantly lower in FM patients than controls. However, no significant difference was seen in serum NO levels between the two groups. A significant correlation was evident between serum NO level and pain. Additionally, the correlation between glutathione level and morning stiffness was found to be significant. These findings support other studies, we assume that these two antioxidants might have impact on the pathogenesis of FM disease.     

Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children

Levels of exhaled nitric oxide (eNO) are elevated in subjects with asthma and fall in response to oral or inhaled steroids. This study explored the possibility the measurement of eNO levels could be used to identify subjects who were not adhering to their treatment regimen. Twenty children with asthma attending the respiratory clinic were recruited. Each attended on four occasions 1 month apart when eNO levels were measured. A data logger attached to a pressurised metered dose inhaler was used to objectively monitor use of inhaled corticosteroids (ICSs). The correlation between day and dose compliance with eNO was assessed. The data demonstrated a weak but non-significant correlation between eNO and both day (r = 0.055, P = 0.67) and dose (r = 0.153, P = 0.23). A recorded value of eNO less than 12 was associated with day compliance rates of 3-97%. Of the 19 recorded eNO values greater than 12 ppb almost 80% were from subjects with a day compliance of less than 50% during the preceding month. Of the four values greater than 12 ppb and day compliance > 60% one subject had a poor inhaler technique, one had a mild viral exacerbation and one appeared to be associated with increase pollen exposure. The measurement of eNO may prove to be a useful tool in helping to manage children with asthma but further work is required to define its precise role. Elevated eNO levels in asthmatic children taking ICSs are likely to reflect poor compliance but confounding factors such as disease activity and inhaler technique need to be carefully considered.     

Serum prolidase activity,oxidative stress,and nitric oxide levels in patients with bladder cancer

Objectives

Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity.

Design and methods

Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined.

Results

Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05).

Conclusions

Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.

     

Increase in nitric oxide urinary products during gluten challenge in children with coeliac disease

BACKGROUND: Coeliac disease is a gluten-sensitive enteropathy where pro-inflammatory cytokines and excess nitric oxide (NO) production can contribute to mucosal damage. NO urinary products are elevated in coeliac children on a gluten diet, but it is not known how rapidly this increase develops after gluten exposure. METHODS: Oral gluten challenge was performed in 25 children whose families kept a daily record of gluten intake and symptoms. Blood was analysed monthly for antigliadin (AGA) and endomysium antibodies (EMA). Urine was analysed every second week for NO products, i.e. the sum of nitrite and nitrate was measured with a colorimetric method. We performed a third biopsy when clinical symptoms indicated a relapse. Median age at the post-challenge biopsy was 3.8 (2.7-8.8) years. RESULTS: Signs of morphological or serological relapse were seen in all children. Mean daily gluten intake was 0.10 (range 0.02-0.26) g/kg bodyweight. Median NO level was doubled and significantly higher after 4 weeks of challenge but not after 2 weeks. EMA, but not AGA levels, correlated positively with NO. Intraepithelial lymphocyte count was significantly higher in the post-challenge biopsy, but did not correlate with the NO levels. CONCLUSIONS: NO products in urine increased during gluten challenge. EMA levels reflected severity of mucosal damage, and NO products reflected the inflammatory response, which was doubled after 4 weeks of challenge. The NO analysis is simple and non-traumatic for the child. It can be performed repeatedly during investigation of children with suspected coeliac disease.     

Changes in exhaled nitric oxide levels with immunotherapy.

The mechanisms by which immunotherapy (IT) modulates allergic airway response are not entirely clear. Exhaled nitric oxide (eNO) is a sensitive marker of airway inflammation in allergic respiratory disorders. We hypothesize that eNO may serve as a barometer of the immunomodulatory changes occurring during IT. We aimed to characterize the pattern of eNO levels in children undergoing traditional IT (TradIT) and rush IT (RushIT). Off-line measurements of eNO were obtained in children electing to undergo RushIT or TradIT at a University-based Allergy/Asthma Clinic. The eNO was measured before IT (pre-IT, week 0) was initiated, and at 2, 4, 6, 8, and 12 weeks after starting IT. Nine children received TradIT and 10 children received RushIT. Pre-IT eNO in the RushIT group averaged 12.6 parts per billion (ppb). This was followed by a rise to 17.7 ppb at week 2. The elevated eNO levels persisted till week 8, and then dramatically dropped below the pre-IT values to 8.9 ppb at week 12 (p = 0.038). Similar changes in eNO were not seen in the TradIT group. The difference in eNO levels between the two groups was most marked at 4 weeks (p = 0.014). Initiation of IT produces significant immunomodulatory changes such as a rise in eNO levels. Temporally, the changes appear to be accelerated in the RushIT group compared with the TradIT group, with return to baseline as maintenance IT levels are achieved.     

Antibody testing in Indian children with celiac disease.

BACKGROUND: We prospectively evaluated the usefulness of IgA tissue transglutaminase antibodies (IgA tTG) in the initial diagnosis of celiac disease (CD) and compared its diagnostic potential with that of IgA anti-endomysial antibodies (IgA EMA) and anti-IgA and IgG gliadin antibodies (AGA and AGG, respectively). METHODS: Sera of 23 untreated children fulfilling the revised ESPGHAN criteria for diagnosis of CD (Group I; mean age 10.8 y); 19 disease controls (Group II; mean age 8.5 y) presenting with chronic diarrhea, short stature or both; and 22 healthy children (Group III; mean age 8.8 y) were studied. These were tested in a blinded manner for AGA, AGG, IgA tTG (guinea pig as antigen) and IgA EMA. RESULTS: In Group I, IgA EMA was positive in 19, IgA tTG in 17, AGA in 14 and AGG in 17 patients. In Group II, these tests were positive in 1, 0, 2 and 14 patients, respectively and in Group III, in 0, 0, 0 and 1 child, respectively. Analyzing data from Group I and II, IgA EMA, IgA tTG, AGA and AGG had sensitivity rates of 83%, 74%, 61% and 74%, respectively; the specificity rates were 95%, 100%, 89% and 26%; positive predictive values were 95%, 100%, 88% and 55% and negative predictive values were 82%, 74%, 65% and 45%, respectively. CONCLUSION: IgA tTG is useful for the diagnosis of CD, with sensitivity and specificity rates comparable to those of EMA and this test is well suited for use in tropical countries like India.