Adenosine has profound effects on immune cells and has been implicated in the intrathymic apoptotic deletion of T-cells during development. In order to characterize adenosine effects on quiescent peripheral blood mononuclear cells (PBMC), we have evaluated the ability of the previously characterized adenosine receptor agonist 2-chloro-adenosine (2CA; Ceruti, Barbieri et al., 1997) and of the antineoplastic drug 2-chloro-2'-deoxy-adenosine (2CdA, cladribine) to trigger apoptosis of PBMC. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and appearance of hypodiploid DNA peak by flow cytometry. 2CA (10 microM) and 2CdA (1 microM) induced apoptosis in human PBMC, which are relatively insensitive to apoptosis. For both agents, the effect was concentration- and time-dependent, although 2CdA induced apoptosis more potently than 2CA. Evaluation of mitochondrial function in parallel samples using the mitochondrial membrane-potential-specific dye JC-1 showed that mitochondrial damage followed the same kinetics as apoptosis, hence an early damage of mitochondria is likely not responsible for adenosine-induced death of PBMC. The effect of 2CA was partially prevented by addition of dipyridamole (DP), a nucleoside transport inhibitor, hence some of the apoptotic effect of this nucleoside is, at least in part, due to intracellular action. Alternatively, DP did not affect 2CdA-induced apoptosis, suggesting that 2CdA may enter cells via a DP-insensitive transporter. 5-Iodotubercidin (5-Itu), a nucleoside kinase inhibitor, was also able to partially prevent the action of 2CA and was not able to affect 2CdA-induced apoptosis, suggesting a different role for phosphorylation in 2CA- vs 2CdA-induced apoptosis. To test the role of P1 receptors, agonists and antagonists selective at various P1 receptor subtypes were used. Data suggest that, for 2CA, apoptosis is partially sustained by activation of the A2A receptor subtype, whereas no role is exerted by P1 receptors in 2CdA-dependent apoptosis. Moreover, in these cells, apoptosis could also be triggered through intense activation of the A3 receptor via selective agonists such as 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), but this mechanism plays no role in either 2CA- or 2CdA-induced apoptosis. On the whole, our results suggest that 2CA and 2CdA follow different pathways in inducing apoptosis of immune cells. Moreover, our data also suggest that there are at least three different ways by which adenosine derivatives may induce apoptosis of human PBMC: (i) through an A2A-like extracellular membrane receptor; (ii) through entry of nucleosides into cells and direct activation of intracellular events involved in the apoptotic process; or (iii) through activation of the A3 receptor.

2-Chloroadenosine↗

PubMedDate not supplied

Chronic idiopathic hyperphosphatasia and fibrous dysplasia in the same child.

A generalized skeletal dysplasia with features of chronic idiopathic hyperphosphatasia and fibrous dysplasia of the mandible were observed in a 6-year-old child. The abnormal development of the bones resulted from enhanced remodeling and the failure of mature bone to form. The occurrence of the two lesions in the same child and a review of the literature support the hypothesis that pathogenesis of fibrous dysplasia and idiopathic hyperphosphatasia reflect an underlying common defect in the control of bone cell activity.

Diagnosis, Differential↗

PubMedDate not supplied

[Treatment of unspecific ulcerative rectocolitis in a child with enemas containing butyrate. Case report].

OBJECTIVE: To report a promising therapy to ulcerative colitis in children. METHODS: We report a case of ulcerative colitis in 4 years old female, who had this diagnosis since she was 1 year old. The treatment of RCU1 had an unsatisfactory response to conventional therapies (rectal and oral corticosteroids and immunosuppressive agent). RESULTS: She showed improvement, using enemas containing butyrate, in clinical, endoscopic and histological parameters. CONCLUSIONS: Although the role of butyrate in the treatment of ulcerative colitis still remains to be determined, we find effective response in this case. Despite evidences that butyrate may be beneficial and safety in treating refractory distal ulcerative colitis, results of controlled trials, specially in children will be necessary to prove the efficacy of this therapy.

Administration, Oral↗

PubMedDate not supplied

[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.

Antibodies↗

PubMedDate not supplied

[Protein hydrolysate as a dietetic resource]

OBJECTIVE: The central goal of this paper was to study the application of beef meat and poultry (turkey and chicken) hydrolysates to the preparations used in our Brazilian current feeding practices. METHODS: The various kinds of meat were hydrolyzed with fresh pineapple under similar conditions to those daily used at home. The selection of three types of preparation was dependent on whether their contents included starch or gelatin and liquid, like soup, mousse and fruit-shake. Hydrolysate were added to the preparations as part of the liquid content of their recipes. The acceptability of the preparations was checked out by employing the hedonic-scale affective test with untrained tasters. Variance analysis and the Tukeýs test were performed with a 5% level of significance for the results.RESULTS: The selected recipes were the following: bitterroot soup, fruit and vegetable-shakes and grape mousse, all of them containing starch or gelatin as an element to camouflage the bitter taste of the aminoacids. The preparations were well accepted: approximately 76% of the tasters reported having liked the soup at least somewhat; as to the shakes, more than 50% gave positive answers, and as to the mousse, approximately 88% reported having liked it. There were no statistically significant differences (p< 0.05) concerning the application of the three hydrolysates in all the preparations tested. CONCLUSIONS: The use of hydrolysed meat to replace liquid content of recipes is highly practicable, requiring only an adequate selection of recipes and their ingredients, that should include starch and gelatin in order to get fully satisfactory products. These preparations might serve as a basis for other ones, adapted to each diet.

Journal Article↗

PubMedDate not supplied

[Prolonged esophageal pH monitoring in preterm infants: a challenge]

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Editorial↗

PubMedDate not supplied

[Immunohistological study of T-lymphocytes (total and helper) and B-lymphocytes of the colonic mucosa in children with Crohn's disease and non-specific ulcerative colitis].

For one to understand better the immunological mechanism in the colonic mucosae of inflammatory bowel disease, 19 children with ulcerative colitis and 12 children with Crohn's disease were studied. The inflammatory cells identified by the immunoperoxidase technique and specific markers for total T lymphocytes (CD3), helper T lymphocytes (CD4) and B lymphocytes (CD20) in differents evolutionary periods of the disease were analysed. PI (before treatment), PII (until two years of treatment) and PIII (with more than two years of treatment). In general, all marker studied in this research, presented higher averages if comparing to the control group with different degrees of significance in the different studied periods. The marker CD3, of the total T lymphocyte, increased in the epithelial (superficial and glandular) and in the lamina propria of the involved mucosae in relation to the controlled ones, was diffusely distributed over the mucosae, concentrating itself around the microgranulomas and the nodules lymphoids. In Crohn's disease, PI, its average differed significantly from the controlled ones. Similar behave was seen in the marker CD20 of the lymphocytes in the involved mucosae, whole averages were superior in relation to the controlled ones; thought, only in the PI of the Crohn's disease this difference had been significant. The immunochromatic cells CD3 distributed themselves diffusely over the involved mucosae, concentrating themselves in the interior of the lymphoides nodules and in the injured areas, near the macrophages. The marker CD4, of helper T lymphocyte also presented in the involved mucosae high averages in relation to the controlled mucosae, but without estatistic significance. The CD4 cells distributed themselves diffusely over the whole thickness of the involved mucosae, concentrating themselves around the lymphoids nodules and microgranulomas. These results confirm the participation of these elements in the pathogenesis of inflammatory bowel disease, but did not permit the establishment of any discriminatory criteria between ulcerative colitis and Crohn's disease. The results of positive correlation between the increased of CD4 and CD20 in ulcerative colitis and CD3 and CD20 in Crohn's disease show clearly the immunoregulation action of the CD4+ cells over clonal expansion and the differenciation of the B lymphocytes from plasmocytes and the IgG syntese.

Adolescent↗