Should We Assess Vitamin D Status in Pediatric Patients With Celiac Disease?

OBJECTIVES: Screening for vitamin D status in celiac disease (CD) has been recommended but the literature provides varying support. We sought to assess the vitamin D status in newly diagnosed children with CD and in a non-CD control population and relate them to vitamin D intake. METHODS: In a cross-sectional study, serum 25-hydroxyvitamin D (25-OHD) levels were drawn in children with newly diagnosed CD and compared with pediatric outpatients with functional abdominal complaints. Anthropometric data as well as vitamin D intake based on milk and multivitamin ingestion were collected. RESULTS: Thirty-eight newly diagnosed CD patients (10.4 ±â€Š3.0 years old; 50% girls) and 82 controls (11.2 ±â€Š4.2 years old; 58.5% girls) were studied. Both groups were similar except for average daily D intake and BMI. There was no statistical difference in mean 25-OHD levels between CD (26.4 ±â€Š8.0 ng/mL) and controls (23.5 ±â€Š8.2 ng/mL) [P ≤ 0.07]. Both groups had high percentages of suboptimal D status (65.8% CD and 79.3% controls). 25-OHD levels significantly correlated with age (r = -0.262; P < 0.0038) and estimated vitamin D intake (r = 0.361; P < 0.0001). CONCLUSIONS: No significant difference in 25-OHD levels was noted between newly diagnosed CD and controls, but inadequate 25-OHD levels were common in both. 25-OHD levels were highly associated with vitamin D intake demonstrating similar vitamin D absorption between patients and controls. As CD is associated with bone disease and D status is frequently low, efforts at optimizing D, such as screening levels at diagnosis need to be conducted.

Vitamin D in pediatric gastrointestinal disease.

PURPOSE OF REVIEW: The purpose of this review is to examine the prevalence of vitamin D deficiency in pediatric gastrointestinal disease, specifically celiac disease and inflammatory bowel disease (IBD); to discuss the role of vitamin D and its deficiency in gastrointestinal disease pathophysiology; and to present current literature regarding diagnosis and treatment of vitamin D deficiency in these pediatric gastrointestinal diseases. RECENT FINDINGS: Vitamin D deficiency is common in children with gastrointestinal symptoms and disease processes. In celiac disease, vitamin D status should be routinely assessed at the time of diagnosis and during subsequent follow up if deficient. There is growing evidence to suggest an inverse association between vitamin D and IBD activity; however, the therapeutic role of vitamin D in IBD patients requires further investigation. SUMMARY: Suboptimal vitamin D status commonly occurs in children with gastrointestinal disease. It is advisable to check serum 25-hydroxy vitamin D levels in children with newly diagnosed celiac disease and IBD. In celiac disease, vitamin D status should be assessed during subsequent follow up if deficient. In IBD, 25-hydroxy vitamin D levels should be checked at least yearly. Therapy should be provided to maintain a level of greater than 30 ng/ml but less than 100 ng/ml; however, the ideal vitamin D dosing regimen to treat vitamin D deficiency and to maintain this optimum level remains unknown. The role of vitamin D as a therapeutic agent in IBD is still under investigation.

Mechanisms of modulation of cytokine release by human cord blood monocytes exposed to high concentrations of caffeine.

BACKGROUND: Serum caffeine concentrations >20 µg/ml (100 µmol/l) in infants treated for apnea of prematurity increases TNF-α and decreases IL-10, changes that perhaps are linked to comorbidities. We hypothesize that this proinflammatory cytokine profile may be linked to differential binding of caffeine to adenosine receptor subtypes (AR), inhibition of phosphodiesterases (PDEs), and modulation of toll-like receptors (TLR). METHODS: Lipopolysaccharide-activated cord blood monocytes (CBM) from 19 infants were exposed to caffeine (0-200 µmol/l) with or without previous exposure to A1R, A3R, or PDE IV antagonists to determine changes in dose-response curves. Cytokines levels (enzyme-linked immunosorbent assay (ELISA)), intracellular cyclic adenosine monophosphate (cAMP) accumulation (enzyme immunoassay (EIA)), and TLR gene expression (real time qRT PCR) were measured. RESULTS: Caffeine at ≤100 µmol/l decreased TNF-α levels (~25%, P = 0.01) and cAMP. All caffeine concentrations decreased IL-10 levels (17-35%, P < 0.01). A1R, A3R, and PDE blockades decreased TNF-α (31, 21, and 88%, P ≤ 0.01), but not IL-10. Caffeine further decreased TNF-α following A3R and PDE blockades. Caffeine concentrations directly correlated to TLR4 gene expression (r = 0.84; P < 0.001). CONCLUSION: Neither A3R, nor PDE blockades are involved in caffeine's modulation of cytokine release by CBM at any concentration. Besides A1R blockade, caffeine's upregulation of TLR4 may promote inflammation at high concentrations.

Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants.

OBJECTIVE: To determine changes in cytokine levels associated with caffeine treatment in a cohort of preterm infants. STUDY DESIGN: For this observational prospective study, we collected clinical data from 26 preterm infants (≤ 30 weeks gestational age). In addition to caffeine levels, cytokine profiles in peripheral blood (PB) and tracheal aspirates (TA) were determined with enzyme-linked immunosorbent assay at birth, before and after (at 24 hours and 1 week) initiation of caffeine. Non-parametric statistics were applied. RESULTS: Included infants were 26.9 ± 1.7 weeks gestational age and weighed 985 ± 202 g. At birth, all cytokine concentrations were significantly greater in TA than PB. Serum caffeine levels were 11.1 µg/mL (interquartile range, 1.85) at approximately 24 hours post-load and 16.4 (8.7) µg/mL at 1 week on treatment. At approximately 24 hours post-load, interleukin (IL)-10 levels decreased by 47.5% (P = .01) in PB and 38.5% (P = .03) in TA, whereas other cytokine levels remained unchanged. At 1 week, caffeine levels were correlated (U-shaped) with changes in proinflammatory tumor necrosis factor-α (R(2) = 0.65; P = .0008), interleukin (IL)-1ß (R(2) = 0.73; P = .0007), and IL-6 (R(2) = 0.59; P = .003), whereas inversely correlated (linear) with the anti-inflammatory IL-10 (R(2) = 0.64; P = .0008). Altogether, caffeine, at serum levels ≥ 20 µg/mL, was associated with a proinflammatory profile after 1 week of treatment. CONCLUSIONS: Caffeine treatment for apnea of prematurity correlates with changes in cytokine profile. Caffeine levels ≥ 20 µg/mL are associated with a proinflammatory profile in our cohort of preterm infants.

Caffeine modulates TNF-alpha production by cord blood monocytes: the role of adenosine receptors.

Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A1R), ZM241385(A2aR), MRS1754(A2bR), and MRS1220(A3R). After 48 h in culture, A2aR and A2bR gene expression increased 1.9 (p = 0.04) and 2.5-fold (p = 0.003), respectively. A1R protein expression directly correlated with increasing LPS concentrations (p = 0.01), with minimal expression preexposure. Only caffeine (50 microM) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-alpha) release from LPS activated-CBM by 20 and 25% (p = 0.01) and TNF-alpha gene expression by 30 and 50%, respectively, in conjunction with a > or =2-fold increase in cAMP (p < 0.05). AR blockade did not modulate other measured cytokines. The induction of A1R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A1R blockade, increases cAMP production and inhibits pretranscriptional TNF-alpha production by CBM.

Triple Diagnosis of Crohn's Disease, Celiac Disease, and Eosinophilic Esophagitis in a Child With Siderius-Hamel Syndrome.

Siderius-Hamel syndrome is a rare condition characterized by intellectual disability and distinct facial features. Crohn's disease-related eosinophilic esophagitis (EoE) has been reported; however, an association between celiac disease and EoE remains controversial. We present a case of a child with Siderius-Hamel syndrome who had characteristic findings of all these conditions-Crohn's disease, celiac disease, and EoE-an occurrence that to our knowledge has not been reported previously. The purpose of this report is to make physicians aware of this rare occurrence, so that it can be kept in mind while evaluating a patient with Siderius-Hamel syndrome presenting with gastrointestinal complaints.

Eosinophilic gastroenteritis: Atypical cause for chronic diarrhea in human immunodeficiency virus-associated immunosuppression.

Eosinophilic gastroenteritis (EGE) is an uncommon disease in both immunocompetent and immunocompromised. We describe a 57-year-old male with human immunodeficiency virus who presented to us with chronic diarrhea. He had no history of allergies and had significant weight loss, normal systemic examination, and a complete blood count showing no eosinophilia. After an esophagogastroduodenoscopy, the diagnosis of EGE was made by histopathological findings. The symptoms started improving with the initiation of treatment with oral prednisolone.

Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii.

Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% (P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% (P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% (P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.