Beyond islet trasplantation in diabetes cell terapy:from embryonic stem cells to transdifferentation of adult cells

Exogenous insulin is, at the moment, the therapy of choice of diabetes, but does not allow tight regulation of glucose leading to long-term complications. Recently, pancreatic islet transplantation to reconstitute insulin-producing cells, has emerged as an alternative promising therapeutic approach. Unfortunately, the number of donor islets is too low compared with the high number of patients needing a transplantation leading to a search for renewable sources of high-quality -cells. This review, summarizes more recent promising approaches to the generation of new -cells from embryonic stem cells for transdifferentiation of adult cells, particularly a critical examination of the seminal work by Lumelsky et al

Cell Therapy in Type 1 Diabetes

The incidence of diabetes mellitus has grown exponentially in the last few years. Etiopathogenesis of diabetes implies a ?-cells damage in the islet of Langerhans, either through an autoimmune reaction present in type 1 diabetic patients or through altered function within these cells that affect their ability to secrete a properly functioning insulin hormone, in patients suffering from type 2 diabetes. Exogenous insulin supply is, at the moment, the therapy of choice of the disease but it does not allow tight control of glucose regulation, leading to long-term complications. Over the past few decades, pancreas or pancreas-kidney organ transplantation has been the most effective treatment for severe diabetic patients. Recently, an alternative promising therapeutic approach, consisting of successful pancreatic islet transplantation to reconstitute the insulin producing ? cells, has also emerged. Unfortunately the number of donor islets is too low compared to high number of patients needing a transplant, so the search for new renewable sources of high-quality ?-cells becomes highly topical. In this review, starting from the description of state of art of islet transplantation, we summarize the more recent promising approaches to the generation of new ?-cells giving a big enfacy to adult stem/progenitor cells

Dissecting the different biological effects of oncogenic Ras isoforms in cancer cell lines: could stimulation of oxidative stress be the one more weapon of H-Ras? Regulation of oxidative stress and Ras biological effects

Ras proteins are small GTPase functioning as molecular switches that, in response to particular extracellular signalling, as growth factors, activate a diverse array of intracellular effector cascades regulating cell proliferation, differentiation and apoptosis. Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) activated by point mutations which contribute to malignant phenotype, including invasiveness and angiogenesis. Despite the common signalling pathways leading to similar cellular responses, studies clearly demonstrate unique roles of the Ras family members in normal and pathological conditions and the lack of functional redundancy seems to be explainable, at least in part, by the ability of Ras isoforms to localize in different microdomains to plasma membrane and intracellular organelles. This different intracellular compartmentalization could help Ras isoforms to contact different downstream effectors finally leading to different biological outcomes. Interestingly, it has also been shown that Ha- and Ki-Ras exert an opposite role in regulating intracellular redox status. In this regard we suggest that H-Ras specific induction of ROS (reactive oxygen species) production could be one of the main determinants of the invasive phenotype which characterize cancer cells harbouring H-Ras mutations. In our hypothesis then, while K-Ras (not able to promote oxidative stress) could mainly contribute to cancer progression and invasiveness through activation of MAPK and PI3K, H-Ras-mediated oxidative stress could play a unique role in modulation of intercellular contacts leading to a loss of cell adhesion and eventually also to a metastatic spread

Comparison between local and regional anesthesia in arteriovenous fistula creation.

PURPOSE: Assessment of the effectiveness of Brachial Plexus Block (BPB) via axillary approach compared to regional anesthesia for arteriovenous fistula surgery in patients affected by end-stage renal disease. METHODS: We compared forty patients randomly divided into two groups. Group A underwent BPB procedure with 15 mL ropivacaine 1% and 10 mL of saline (0.9% NaCl) via axillary approach. Group B received local anesthesia with lidocaine 2%. The forearm blood vessels were assessed by Doppler ultrasonography before and after the intervention. RESULTS: BPB performed on Group A was associated with a considerable venous dilation and a significant decrease (48.7%, P<.05) in pulsatility index (PI) measured by Doppler ultrasound. In Group B, PI and venous dilation remained unaltered in the postoperative phase. No complications such as thrombosis or occlusion were encountered among patients who underwent BPB. CONCLUSIONS: The axillary-approached BPB was more advantageous than local anesthesia. Its effectiveness was because of venous dilation and the decrease in the PI, consequent to the reduction in peripheral resistances and the increase in local blood flow, thus offering an ideal background for fistula creation and short-term patency

Is secondary hyperparathyroidism-related myelofibrosis a negative prognostic factor for kidney transplant outcome?

Secondary hyperparathyroidism (HP) presenting with hypocalcemia and subsequent increased parathormone (PTH), is mainly identified in patients with chronic renal failure, which has been associated with variable degrees of bone marrow fibrosis. For suitable patients with end-stage renal disease (ESRD), kidney transplantation is recognized as the therapy of choice, being superior to dialysis in terms of quality of life and long-term mortality risk; in this regard interesting data show that increased time on dialysis prior to kidney transplantation is associated with decreased graft and patient survival. In our opinion an important and until now underestimated determinant of graft survival is the proper activity of bone marrow because of the emerging role of hematopoietic stem cells (HSC) in repair of ischemia/reperfusion (IR) damage. We postulate that in ESRD patients, who usually undergo long dialytic treatment, a myelofibrosis caused by an overt secondary HP could drastically decrease the HSC potential for IR damage repair after kidney transplant; this could irremediably lead to a delay in graft function with all related complicances. If the curative role of bone marrow-derived stem cells was confirmed by more data obtained in experimental animal models, it could be possible to try a cellular-based therapeutic approach in the management of ESRD patients which are in waiting list for a kidney transplant

THE MEDITERRANEAN DIET: A HISTORY OF HEALTH

The Mediterranean tradition offers a cousine rich in colors, aromas and memories, which support the taste and the spirit of those who live in harmony with nature. Everyone is talking about the Mediterranean diet, but few are those who do it properly, thus generating a lot of confusion in the reader. And so for some it coincides with the pizza, others identified it with the noodles with meat sauce, in a mixture of pseudo historical traditions and folklore that do not help to solve the question that is at the basis of any diet: combine and balance the food so as to satisfy the qualitative and quantitative needs of an individual and in a sense, preserves his health through the use of substances that help the body to perform normal vital functions. The purpose of our work is to demonstrate that the combination of taste and health is a goal that can be absolutely carried out by everybody, despite those who believe that only a generous caloric intake can guarantee the goodness of a dish and the satisfaction of the consumers. That should not be an absolute novelty, since the sound traditions of the Mediterranean cuisine we have used for some time in a wide variety of tasty gastronomic choices, from inviting colors and strong scents and absolutely in line with health

Towards an ideal source of mesenchymal stem cell isolation for possible therapeutic application in regenerative medicine

Background. The possibility of obtaining mesenchymal stem cells (MSCs) from fetal tissue such as amniotic fluid, chorionic villi and placenta is well-known and a comparison between MSCs originating in different sources such as fetal tissue and those from bone marrow in terms of yield and function is a topical issue. The mesenchymal stem cells isolated from bone marrow are well-characterized. Unfortunately the low quantitative yield during isolation is a major problem. For this reason, other tissue sources for MSCs are of paramount importance. Conclusion. In this review, starting from a description of the molecular and cellular biology of MSCs, we describe alternative sources of isolation other than bone marrow. Finally, we describe the potential therapeutic application of these cells

THE INTESTINAL ECOSYSTEM AND PROBIOTICS

The term "probiotic" comes from the greek "pro bios" and means "pro life": Nowadays, an increasing number of pharmaceutical preparations and functional foods are enriched with probiotics and for the patients it is increasingly important to receive information needed to know how to orient in the choice. The benefits from probiotics are many and include the modulation of the intestinal microflora (stimulation of beneficial bacteria and inhibition of pathogens), the support of bowel function and the stimulation of the immune system. This broad spectrum of beneficial effects to maintain efficient the intestinal ecosystem. Therefore, probiotics are an useful tool to prevent the formation of disorders and/or pathologies. The aim of this review is to describe the intestinal ecosystem and how probiotics could be effective in the treatment and prevention of possible alterations