The aim of our study is to analyze factors, including matrix metalloproteinase (MMP) levels, that could influence the integration of dermal grafts in diabetic foot ulcers. From September 2012 to September 2013, 35 diabetic patients with IIA lesion (Texas Wound Classification) and an extensive foot tissue loss were considered suitable for dermal graft. Before the enrollment we ensured the best local conditions: adequate blood supply, control of infection, and offloading. The MMP level of each lesion was evaluated blindly before the application of dermal substitutes. At 1-month follow-up, we analyzed the correlation between clinical patient characteristics, local wound features including MMP levels, dermal substitute applied, and the outcome expressed in terms of dermal graft integration. We observed dermal graft integration in 28/35 patients (80% of our population). In multivariate analysis high MMP level was the only negative predictor for dermal graft integration (P < .0007). In addition, we divided the patients into 2 groups according to MMP levels: group 1 with low protease activity (24 patients) and group 2 with elevated protease activity (11 patients). The integration of the dermal graft was 100% in group 1 (n = 24 patients) and 36.4% in group 2 (n = 4patients), P < .0001. According to our data, the evaluation of MMP levels may be useful to choose the right strategy to get the best results in terms of clinical success and cost saving. However, further studies are necessary to confirm these findings.
Potential celiac disease (CD) is defined by the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies and normal duodenal mucosa. The major clinical problem is the management of asymptomatic patients and how to predict the development of villous atrophy. This prospective longitudinal cohort study describes the natural history of potential CD up to 9 years and explores risk factors associated with the development of mucosal damage.
Autophagy is an evolutionarily conserved process that promotes the lysosomal degradation of intracellular components including organelles and portions of the cytoplasm. Besides operating as a quality control mechanism in steady-state conditions, autophagy is upregulated in response to a variety of homeostatic perturbations. In this setting, autophagy mediates prominent cytoprotective effects as it sustains energetic homeostasis and contributes to the removal of cytotoxic stimuli, thus orchestrating a cell-wide, multipronged adaptive response to stress. In line with the critical role of autophagy in health and disease, defects in the autophagic machinery as well as in autophagy-regulatory signaling pathways have been associated with multiple human pathologies, including neurodegenerative disorders, autoimmune conditions and cancer. Accumulating evidence indicates that the autophagic response to stress may proceed in two phases. Thus, a rapid increase in the autophagic flux, which occurs within minutes or hours of exposure to stressful conditions and is entirely mediated by post-translational protein modifications, is generally followed by a delayed and protracted autophagic response that relies on the activation of specific transcriptional programs. Stress-responsive transcription factors including p53, NF-?B and STAT3 have recently been shown to play a major role in the regulation of both these phases of the autophagic response. Here, we will discuss the molecular mechanisms whereby autophagy is orchestrated by stress-responsive transcription factors.
Celiac disease (CD) is a multifactorial autoimmune disease induced by ingestion of gluten in genetically predisposed individuals. Despite technological progress, the diagnosis of CD is still based on duodenal biopsy as it was 50 years ago. In this study we analysed the expression of CD-associated genes in small bowel biopsies of patients and controls in order to explore the multivariate pathway of the expression profile of CD patients. Then, using multivariant discriminant analysis, we evaluated whether the expression profiles of these genes in peripheral blood monocytes (PBMs) differed between patients and controls.
The aim of our case report was to analyse the results obtained with the Matriderm® system and autologous skin grafting for the surgical treatment of skin necrosis of scrotum as a result of endovascular embolisation. We recruited one patient with scrotum skin necrosis as a result of endovascular embolisation admitted at the department of Plastic and Reconstructive Surgery, University of Rome Tor Vergata. The patient underwent Matriderm® system and autologous skin grafting for skin necrosis treatment. After a single treatment, reduction of the skin necrosis was obtained, after 30 days from the surgical treatment. Patient experienced a reduction in pain and a complete restoration of the loss in volume and quality of skin was noticed. Matriderm® system and autologous skin grafting is a simple, safe and feasible technique. When comparing this treatment with others, Matriderm® is a simpler, more economic and less time-consuming method, and does not require sophisticated laboratory facilities.
Celiac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate of the CD risk in siblings, by adding to HLA a small set of non-HLA genes. One-hundred fifty-seven Italian families with a confirmed CD case and at least one other sib and both parents were recruited. Among 249 sibs, 29 developed CD in a 6 year follow-up period. All individuals were typed for HLA and 10 SNPs in non-HLA genes: CCR1/CCR3 (rs6441961), IL12A/SCHIP1 and IL12A (rs17810546 and rs9811792), TAGAP (rs1738074), RGS1 (rs2816316), LPP (rs1464510), OLIG3 (rs2327832), REL (rs842647), IL2/IL21 (rs6822844), SH2B3 (rs3184504). Three associated SNPs (in LPP, REL, and RGS1 genes) were identified through the Transmission Disequilibrium Test and a Bayesian approach was used to assign a score (BS) to each detected HLA+SNPs genotype combination. We then classified CD sibs as at low or at high risk if their BS was respectively < or ? median BS value within each HLA risk group. A larger number (72%) of CD sibs showed a BS ? the median value and had a more than two fold higher OR than CD sibs with a BS value < the median (O.R?=?2.53, p?=?0.047). Our HLA+SNPs genotype classification, showed both a higher predictive negative value (95% vs 91%) and diagnostic sensitivity (79% vs 45%) than the HLA only. In conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool to improve the prediction of the disease in a cohort of first degree relatives, particularly in the low HLA risk groups.
MiRNAs play a relevant role in regulating gene expression in a variety of physiological and pathological conditions including autoimmune disorders. MiRNAs are also important in the differentiation and function of the mouse intestinal epithelium. Our study was aimed to look for miRNA-based modulation of gene expression in celiac small intestine, and particularly for genes involved in cell intestinal differentiation/proliferation mechanisms. A cohort of 40 children (20 with active CD, 9 on a gluten-free diet (GFD), and 11 controls), were recruited at the Paediatrics Department (University of Naples Federico II). The expression of 365 human miRNAs was quantified by TaqMan low-density arrays. We used bioinformatics to predict putative target genes of miRNAs and to select biological pathways. The presence of NOTCH1, HES1, KLF4, MUC-2, Ki67 and beta-catenin proteins in the small intestine of CD and control children was tested by immunohistochemistry. The expression of about 20% of the miRNAs tested differed between CD and control children. We found that high miR-449a levels targeted and reduced both NOTCH1 and KLF4 in HEK-293 cells. NOTCH1, KLF4 signals and the number of goblet cells were lower in small intestine of children with active CD and in those on a GFD than in controls, whereas more nuclear beta-catenin staining, as a sign of the WNT pathway activation, and more Ki67 staining, as sign of proliferation, were present in crypts from CD patients than in controls. In conclusion we first demonstrate a miRNA mediated gene regulation in small intestine of CD patients. We also highlighted a reduced NOTCH1 pathway in our patients, irrespective of whether the disease was active or not. We suggest that NOTCH pathway could be constitutively altered in the celiac small intestine and could drive the increased proliferation and the decreased differentiation of intestinal cells towards the secretory goblet cell lineage.
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.
Potential celiacs have the celiac type HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.
Mortons neuroma is an entrapment neuropathy of the plantar digital nerve. We treated five patients with wound dehiscence and tendon exposure, after Mortons neuroma surgery excision using a dorsal approach. In this article we describe our technique. From July 2010 to August 2011, at the Department of Plastic and Reconstructive Surgery, University of Rome Tor Vergata, five patients (four females and one male), with ages ranging between 35 and 52 years, were treated with a combination of PRP (platelet rich plasma) and HA (hyaluronic acid). Thirty days following surgery, all patients showed a complete healing of the wound. The use of this technique for the treatment of postoperative wound dehiscence and tendon exposure has proven as satisfactory.
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