Rapid Anti-tTG-IgA Screening Test for Early Diagnosis of Celiac Disease in Pediatric Populations.

A large number of patients with celiac disease (CD) remain undiagnosed because they do not fulfill the criteria for entry into the conventional diagnostic workflow. This study evaluated the clinical utility of anti-tissue transglutaminase IgA antibody lateral flow immunoassays (anti-tTG-IgA LFIA) in the undiagnosed-CD-based pediatric population and the impact of a gluten-free diet (GFD) on screening-detected CD. A total of 576 volunteers were tested for anti-tTG-IgA. Gluten consumption habits, CD related symptoms, and risk factors for CD development were evaluated. Volunteers testing positive for anti-tTG-IgA were referred to the conventional CD diagnostic workflow, and the impact of the GFD on health-related quality of life (HR-QoL) was measured. Among them, 13 had a positive anti-tTG-IgA LFIA test result: 11 had confirmed CD (1.91%), one refused confirmatory tests, and another is undergoing diagnosis. Regarding the CD prevalence, no significant differences were observed among risk (1.89%) and symptomatic (2.65%) groups and the entire tested population (1.55%). Rapid anti-tTG-IgA LFIAs could be of clinical utility in primary care for the early identification of children with CD unidentified by the conventional diagnostic workflow. It could potentially reduce the costs of undiagnosed CD, avoiding unnecessary referrals to gastroenterologists, reducing diagnosis delays and long-term problems, and improving patients' HR-QoL.

Alterations of the growth plate in chronic renal failure.

Chronic renal failure modifies the morphology and dynamics of the growth plate (GP) of long bones. In young uremic rats, the height of cartilage columns of GP may vary markedly. The reasons for this variation are unknown, although the severity and duration of renal failure and the type of renal osteodystrophy have been shown to influence the height of GP cartilage. Expansion of GP cartilage is associated with that of the hypertrophic stratum. The interference of uremia with the process of chondrocyte differentiation is suggested by some morphological features. However, analysis by immunohistochemistry and/or in situ hybridization of markers of chondrocyte maturation in the GP of uremic rats has yielded conflicting results. Thus, there have been reported normal and reduced mRNA levels for collagen X, parathyroid hormone/parathyroid hormone-related peptide receptor, and matrix metalloproteinase 9, as well as normal mRNA and protein expression for vascular endothelial growth factor and chondromodulin I, peptides related to the control of angiogenesis. In addition, a decreased immunohistochemical signal for growth hormone receptor and low insulin-like growth factor I mRNA in the proliferative zone of uremic GP are supportive of reduced chondrocyte proliferation. Growth hormone treatment improves chondrocyte maturation and activates bone metabolism in the primary spongiosa.

Insulin-like growth factor I administration in young rats with acute renal failure.

The outcome of ischemic acute renal failure (IARF) is better in young than adult rats. Insulin-like growth factor I (IGF-I) treatment may increase mortality of adult rats with IARF, probably because of an exaggerated inflammatory response. We report the response to IGF-I therapy in young rats with IARF. Male rats, aged 28+/-1 days, with IARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (IGF) or were untreated (ARF). Sham-operated rats were used as controls. At 2 and 7 days after ischemia, serum urea nitrogen and histological damage score, cell proliferation, apoptosis, neutrophil infiltration, and IGF-I receptor mRNA in kidneys were analyzed. The degree of renal failure, mortality rate, histological damage, cell proliferation, and neutrophil infiltration were not different between IGF-I and ARF rats. Hence, short-term IGF-I treatment did not modify the course of IARF in young rats.

Growth plate height of uremic rats is influenced by severity and duration of renal failure.

To understand the changes induced by uremia in the epiphyseal growth plate, two studies were performed in young rats. In study 1, the morphological features of the tibial growth cartilage of stunted rats with different degrees of reduction of renal function were analyzed 2 weeks after nephrectomy and compared with control rats. There was a negative ( r=-0.549, P<0.05) correlation between serum urea nitrogen (SUN) concentrations and longitudinal growth rate. The heights (mean+/-SEM) of growth cartilage (564+/-32 vs. 366+/-9 microm) and its hypertrophic zone (321+/-25 vs. 157+/-6 microm) were greater ( P<0.05) in uremic than control rats and were highly and positively correlated ( r=0.604, P<0.03 and r=0.706, P<0.01) with SUN levels. In study 2, the time course of growth plate alterations was investigated in uremic rats sacrificed 1 (NX-1), 2 (NX-2), and 4 weeks (NX-4) after nephrectomy compared with their corresponding control animals (C-1, C-2, C-4). Growth cartilage and hypertrophic zone heights were greater in NX-2 (533+/-60 and 264+/-32 microm) than in C-2 (345+/-10 and 131+/-11 microm), with no significant differences in the other groups. This report shows that enlargement of the growth plate and its hypertrophic stratum is greatly, although not exclusively, influenced by the severity and duration of renal insufficiency.

Chondromodulin-I expression in the growth plate of young uremic rats.

BACKGROUND: Growth retardation of chronic renal failure is associated with alterations in the growth plate suggestive of a disturbed chondrocyte maturation process and abnormal vascular invasion at the chondro-osseous interphase. Chondromodulin I (ChM-I) is a potent cartilage-specific angiostatic factor. Its pattern of expression in the uremic rat growth plate is unknown. Persistence of ChM-I synthesis and/or imbalance between ChM-I and vascular endothelial growth factor (VEGF) expressions might play a role in the alterations of uremic growth plate. METHODS: Growth cartilage ChM-I expression was investigated by immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) in growth-retarded young uremic rats (UREM), control rats, fed ad libitum (SAL) or pair-fed with the UREM group (SPF), and uremic rats treated with growth hormone (UREM-GH). VEGF expression was analyzed by immunohistochemistry. RESULTS: ChM-I and ChM-I mRNA were confined to the proliferative and early hypertrophic zones of growth cartilage. A similar number of chondrocytes per column was positive for ChM-I in the 4 groups. In accordance with the elongation of the hypertrophic stratum in uremia, the distance (X+/-SEM, microm) between the extracellular ChM-I signal and the metaphyseal end of growth cartilage was higher (P < 0.003) in UREM (236 +/- 40) and UREM-GH (297 +/- 17) than in SAL (92 +/- 7) and SPF (113 +/- 6). No differences in ChM-I expression were appreciated by RT-PCR. Similar VEGF positivity was observed in the hypertrophic chondrocytes of all groups. CONCLUSION: In experimental uremia, expansion of growth cartilage does not result from increased or persistent expression of ChM-I or from reduced VEGF expression at the cartilage-metaphyseal bone interphase. GH treatment does not modify ChM-I and VEGF expressions.