- MeSH
- Melanoma, Amelanotic diagnosis therapy MeSH
- Survival Analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Penile Neoplasms diagnosis therapy MeSH
- Prognosis MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
An old saying states that ''children are not little adults" and this certainly holds true for celiac disease, as there are many peculiar aspects regarding its epidemiology, diagnosis, clinical presentations, associated diseases, and response to treatment in pediatric compared to adult populations, to such an extent that it merits a description of its own. In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation. In general, the clinical guidelines for diagnosis recommend starting with specific serologic testing in all suspected subjects, including those suffering from extraintestinal related conditions, and performing upper endoscopy with appropriate biopsy sampling of duodenal mucosa in case of positivity. The latter may be omitted in young patients showing high titers of anti-transglutaminase antibodies. The subsequent management of a celiac patient differs substantially depending on the age at diagnosis and should be based on the important consideration that this is a lifelong condition.
- MeSH
- Celiac Disease * complications diagnosis therapy MeSH
- Child MeSH
- Adult MeSH
- Clinical Protocols MeSH
- Humans MeSH
- Age Factors * MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.
- MeSH
- Adult MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease * MeSH
- Genotype MeSH
- Genotyping Techniques MeSH
- Inflammatory Bowel Diseases genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Polymorphism, Restriction Fragment Length MeSH
- Prevalence MeSH
- Promoter Regions, Genetic * MeSH
- Receptor for Advanced Glycation End Products genetics MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.
- MeSH
- Cytomegalovirus Infections immunology MeSH
- Cytomegalovirus physiology MeSH
- Adult MeSH
- Inflammatory Bowel Diseases immunology virology MeSH
- Epstein-Barr Virus Infections immunology MeSH
- Colon immunology virology MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Disease Progression MeSH
- Prospective Studies MeSH
- Intestinal Mucosa immunology virology MeSH
- Herpesvirus 4, Human physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in immunocompromised subjects, including patients suffering from ulcerative colitis (UC). We, therefore, aimed to investigate virus-specific immunity in UC patients. A cohort of 24 UC patients (14 responders and 10 refractory to therapy) and 26 control subjects was prospectively enrolled to undergo virus-specific serology (by ELISA assay) and assessment of both CD4+ and CD8+ virus-specific T-cell response (by interferon-γ enzyme-linked immunospotanalysis). In parallel, mucosal viral load was determined by quantitative real-time PCR and the values were correlated with both clinical and endoscopic indexes of activity. For statistics, the t-test, Mann-Withney test, Fisher's exact test and Spearman rank correlation test were applied; p < 0.05 was considered significant. EBV-specific CD4+ and CD8+ T-cell responses were significantly lower in UC patients compared to controls (p < 0.0001 and p = 0.0006, respectively), whereas no difference was found for HCMV-specific T-cell response. When dividing the UC group according to response to therapy, both responders and refractory UC patients showed a deficient EBV-specific CD4+ T-cell response with respect to controls (p < 0.04 and p = 0.0003, respectively). Moreover, both EBV and HCMV mucosal loads were significantly higher in refractory UC than in responders and controls (p = 0.007 and 0.003; and p = 0.02 and 0.001, respectively), and correlated with activity indexes. Steroid therapy seemed the main risk factor for triggering EBV colitis. Finally, no cases of IgM positivity were found in the study population. An impaired EBV-specific immunity was clearly evident in UC patients, mostly in those refractory to therapy. The ELISPOT assay may serve as new tool for quantifying and monitoring virus-specific T-cell immunity in UC.
- MeSH
- CD4-Positive T-Lymphocytes metabolism MeSH
- CD8-Positive T-Lymphocytes metabolism MeSH
- Cytomegalovirus Infections drug therapy immunology MeSH
- Cytomegalovirus immunology physiology MeSH
- DNA, Viral genetics MeSH
- Epstein-Barr Virus Infections drug therapy immunology MeSH
- Humans MeSH
- Prospective Studies MeSH
- Steroids adverse effects therapeutic use MeSH
- Case-Control Studies MeSH
- Colitis, Ulcerative drug therapy immunology virology MeSH
- Viral Load MeSH
- Herpesvirus 4, Human immunology physiology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Delfín
1. vyd. 151 s., [16] s. obr. příl. ; 21 cm
- MeSH
- Human Experimentation history MeSH
- Concentration Camps MeSH
- Physicians ethics MeSH
- Ethics, Medical history MeSH
- Conspectus
- Lékařské vědy. Lékařství
- NML Fields
- dějiny lékařství
- etika, bioetika, lékařská etika
- NML Publication type
- reportáže
BACKGROUND: The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. METHODS: Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry. RESULTS: While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD. CONCLUSIONS: Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.
- MeSH
- Kidney Failure, Chronic * surgery metabolism MeSH
- Renal Dialysis MeSH
- Dialysis Solutions metabolism MeSH
- Child MeSH
- Glucose metabolism MeSH
- Humans MeSH
- Peritoneal Dialysis * adverse effects MeSH
- Peritoneum metabolism MeSH
- Peritonitis * metabolism MeSH
- Kidney Transplantation * adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Ultrafiltration decline is a progressive issue for patients on chronic peritoneal dialysis (PD) and can be caused by peritoneal angiogenesis induced by PD fluids. A recent pediatric trial suggests better preservation of ultrafiltration with bicarbonate versus lactate buffered fluid; underlying molecular mechanisms are unknown. METHODS: Angiogenic cytokine profile, tube formation capacity and Receptor Tyrosine Kinase translocation were assessed in primary human umbilical vein endothelial cells following incubation with bicarbonate (BPDF) and lactate buffered (LPDF), pH neutral PD fluid with low glucose degradation product content and lactate buffered, acidic PD fluid with high glucose degradation product content (CPDF). Peritoneal biopsies from age-, PD-vintage- and dialytic glucose exposure matched, peritonitis-free children on chronic PD underwent automated histomorphometry and immunohistochemistry. RESULTS: In endothelial cells angiopoietin-1 mRNA and protein abundance increased 200% upon incubation with BPDF, but decreased by 70% with LPDF as compared to medium control; angiopoietin-2 remained unchanged. Angiopoietin-1/Angiopoietin-2 protein ratio was 15 and 3-fold increased with BPDF compared to LPDF and medium. Time-lapse microscopy with automated network analysis demonstrated less endothelial cell tube formation with BPDF compared to LPDF and CPDF incubation. Receptor Tyrosine Kinase translocated to the cell membrane in BPDF but not in LPDF or CPDF incubated endothelial cells. In children dialyzed with BPDF peritoneal vessels were larger and angiopoietin-1 abundance in CD31 positive endothelium higher compared to children treated with LPDF. CONCLUSION: Bicarbonate buffered PD fluid promotes vessel maturation via upregulation of angiopoietin-1 in vitro and in children on dialysis. Our findings suggest a molecular mechanism for the observed superior preservation of ultrafiltration capacity with bicarbonate buffered PD fluid with low glucose degradation product content.
- MeSH
- Angiopoietin-1 metabolism MeSH
- Angiopoietin-2 metabolism MeSH
- Platelet Endothelial Cell Adhesion Molecule-1 metabolism MeSH
- Biopsy MeSH
- Chronic Disease MeSH
- Cytokines metabolism MeSH
- Child MeSH
- Human Umbilical Vein Endothelial Cells MeSH
- Endothelial Cells metabolism MeSH
- Glucose chemistry MeSH
- Bicarbonates chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Lactates chemistry MeSH
- Humans MeSH
- Adolescent MeSH
- Kidney Diseases therapy MeSH
- Peritoneal Dialysis * MeSH
- Peritoneum pathology MeSH
- Buffers * MeSH
- Receptor Protein-Tyrosine Kinases metabolism MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Publication type
- Journal Article MeSH
