Sampling reflex: a relic from the past or a useful parameter for the future?

Techniques in Coloproctology -     

Genetic Insulin Resistance Is a Potent Regulator of Gene Expression and Proliferation in Human iPS Cells

Insulin resistance is central to diabetes and metabolic syndrome. To define the consequences of genetic insulin resistance distinct from those secondary to cellular differentiation or in vivo regulation, we generated induced pluripotent stem cells (iPSCs) from individuals with insulin receptor mutations and age-appropriate control subjects and studied insulin signaling and gene expression compared with the fibroblasts from which they were derived. iPSCs from patients with genetic insulin resistance exhibited altered insulin signaling, paralleling that seen in the original fibroblasts. Insulin-stimulated expression of immediate early genes and proliferation were also potently reduced in insulin resistant iPSCs. Global gene expression analysis revealed marked differences in both insulin-resistant iPSCs and corresponding fibroblasts compared with control iPSCs and fibroblasts. Patterns of gene expression in patients with genetic insulin resistance were particularly distinct in the two cell types, indicating dependence on not only receptor activity but also the cellular context of the mutant insulin receptor. Thus, iPSCs provide a novel approach to define effects of genetically determined insulin resistance. This study demonstrates that effects of insulin resistance on gene expression are modified by cellular context and differentiation state. Moreover, altered insulin receptor signaling and insulin resistance can modify proliferation and function of pluripotent stem cell populations.     

A Peptide from Kiwifruit Exerts Anti-Inflammatory Effects in Celiac Disease Mucosa

Objective: Celiac disease is an immune-mediated disease of the intestine triggered by gluten. Gluten elicits, in genetically susceptible individuals, cytokine responses that are then transmitted to the immunocompetent cells. Vegetables and fruit have anti-inflammatory and antioxidant properties with a protective effect on intestinal epithelium. Kiwifruit is known to have beneficial effects on the intestinal tissues, and it is the only plant food containing the peptide kissper, with anti-inflammatory properties. The aim of this study was the evaluation of the kissper effect on the gluten-induced inflammation in celiac disease.

Methods: We used an in vitro model of intestinal culture explant from celiac disease patients and non-celiac disease patients, cultured for 24 hours with the toxic gliadin peptide P31-43 and kissper preincubation.

Results: Our data showed HLA-DR and TG2 reduction in the celiac disease mucosa pretreated with kissper, as well as a reduction of COX-2 in two patients. No differences we observed for the TGF-b1 and IL-15 levels in supernatants upon kissper pretreatment.

Conclusions: The preliminary results suggest that kissper has a potential anti-inflammatory role in celiac disease.     

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

The demonstration that the small synthetic molecule reversine [2-(4-morpholinoanilino)-N6-cyclohexyladenine] promotes the dedifferentiation of committed cells into multipotent progenitor-type cells has raised hopes on the exploitation of this small chemical tool for the generation of stem cells. Here, we show that reversine causes a failure in cytokinesis and induces polyploidization. These effects of reversine are due to the inhibition of Aurora A and B, two related kinases that are implicated in several aspects of mitosis and that are frequently amplified and overexpressed in human tumors. Reversine inhibits the phosphorylation of histone H3, a direct downstream target of Aurora kinases. Similarly to the Aurora kinase inhibitor VX-680, which has recently entered phase II clinical trials for cancer treatment, reversine inhibited colony formation of leukemic cells from patients with acute myeloid leukemia but was significantly less toxic than VX-680 on cells from healthy donors. The crystal structure of the reversine-Aurora B kinase complex shows that reversine is a novel class of ATP-competitive Aurora kinase inhibitors. Thus, although our studies raise serious doubts on the application of reversine in regenerative medicine, they support the paradigm that reversine might be a useful agent in cancer chemotherapy.     

Preventing seroma formation after axillary dissection for breast cancer: a randomized clinical trial

BackgroundSeroma formation after axillary dissection remains the most common early sequel to breast cancer surgery. Different surgical approaches have been performed to reduce seroma collection. Therefore, we aimed to assess the outcome of patients operated on using an ultrasound scalpel according to a standardized operative technique before accepting it as a routine procedure.MethodsA randomized controlled trial was designed to compare the outcome of patients undergoing breast surgery and axillary dissection using either standard scalpel blades, scissors, ligations, and electrocautery or the ultrasound scalpel only. Each arm of the trial consisted of 30 patients.ResultsA statistically significant benefit in terms of axillary and chest wall drainage volume, the number of axilla seromas, intraoperative bleeding, and hospitalization stay was recorded in the harmonic scalpel group. No significant differences were found between the 2 groups in terms of operative time. Finally, no postoperative hematoma, wound infections, and chest wall seroma were observed.ConclusionsThe use of the harmonic scalpel was shown to reduce the magnitude of seromas in axilla and hospitalization stay. The harmonic scalpel can be used alone in axillary dissection with a safe and effective hemostasis. Our results must be confirmed by larger series.     

The use of a telematic connection for the follow-up of hypertensive patients improves the cardiovascular prognosis

BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect management of hypertensives caused by the lack of interaction between general practitioners (GP) and hypertension specialists. OBJECTIVES: To test the effectiveness on BP and total cardiovascular risk (TCVR) control of an internet-based digital network connecting specialists and GPs. METHODS: We created a network among the Hypertension Clinic, Federico II University (Naples, Italy), 23 hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute Network, CS). Randomized GPs enrolled in CS could update online records of patients (n = 1979). As a control, we included 2045 patients referred to the specialist clinics by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS versus control; P < 0.001 for both] and percentage of patients with BP < 140/90 mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus 47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5 (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS: from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to 3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P < 0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838; 95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the idea that telemedicine can achieve better control of BP and TCVR.     

Immunotherapy targeting colon cancer stem cells

In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as γδ T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication.