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

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

Eight-point Compass Rose Underlay Technique in 72 Consecutive Elderly Patients with Large Incisional Hernia

SummaryBackgroundRepair of incisional hernia (IH) in the elderly is a challenge for the surgeon. Primary closure is preferable but is not always possible because of high recurrence rates of IH repaired without a prosthesis and/or possible respiratory and cardiovascular complications due to extreme tension of the margins. We report our experience with underlay mesh placement in elderly patients with large IH.MethodsA total of 72 patients from January 2003 to December 2009 underwent IH repair involving placement of an intraperitoneal Gore® DualMesh® prosthesis. The prosthesis was first anchored at eight points in a compass rose pattern using a Gore® suture passer and then firmly secured to the abdominal wall with a 360° internal crown running suture.ResultsTwo intraoperative intestinal tears occurred during debridement and were immediately sutured. Postoperative complications included seven seromas, four hematomas, and two infections, one of which was resolved with conservative treatment while one required prosthesis removal.ConclusionThis surgical procedure, like laparoscopic treatment, allows the surgeon to avoid dissection of the abdominal layer and improves prosthesis adhesion with reinforcement of the incisional area near the abdominal defect. The reduction in operation time is remarkable. Despite good results in terms of safety and minimal recurrence for laparoscopy in the management of IH, the use of minimally invasive techniques for large incisional wall defects, especially in elderly patients, is still controversial and practiced by few surgeons. This open technique avoids cardiopulmonary complications arising from pneumoperitoneum in the elderly

Argentum-quarz solution in the treatment of anorectal fistulas: Is it possible a conservative approach?

Patients suffering from chronic intestinal diseases (Crohn's disease, Ulcerative Colitis, Indeterminate Colitis) are prone to the development of pyogenic complications. These complications are most commonly in the form of perianal or intraabdominal abscesses and/or fistulas. The treatment of these complications are managed differently but, after an initial treatment based on medical or minimally invasive management, the solution of the pathological condition is always achieved by a surgical procedure. In the last few years prospective studies have proposed an alternative conservative therapeutic approach based on application of fibrin glue in the healing of patients with fistulas-in-ano. In this paper we suggest and discuss the therapeutic potential of silver and quarz in the conservative treatment of anorectal fistulas pointing out their role in modulating particular steps of the pathogenetic process which characterizes this pathological condition

Enteral nutrition: our experience with percutaneous endoscopic gastrostomy (PEG) and revision of literature

Enteral nutrition (EN), as parenteral nutrition (PN), can be used in cases of patients whose medical conditions prevent the intake of food by mouth; unlike PN, EN keeps the functionality of the digestive tract and it makes home management of patients easier. However, the experience and literature have documented a number of serious complications, fortunately rare, which depend on the methods used in EN realization. We report in this paper our experience in 44 cases of percutaneous endoscopic gastrostomy (PEG), concluding that it is a safe and complications-free procedure. We believe that a nutritional intervention is indicated when, improving nutritional status, patients can obtain a better quality of life and have an average life expectancy

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

A complex case of fatal calciphylaxis in a female patient with hyperparathyroidism secondary to end stage renal disease of graft and coexistence of haemolytic uremic syndrome

Background. Calciphylaxis is a potentially fatal complication of persistent secondary hyperparathyroidism; its cause is still not clear. Unfortunately there is no close relation in severity of clinical picture, serological and pathological alteration. For this reason the prognosis is difficult to establish. Administration of sodium thiosulphate may reduce the precipitation of calcium crystals and improve the general clinical conditions before surgical parathyroidectomy, which seems the only therapeutic approach able to reduce the mortality risk in these patients. Methods and Results. A 60 year old female patient suffering from End Renal Stage Disease, on haemodialysis from 2001 due to the onset of haemolytic uremic syndrome, underwent a kidney transplant in April 2008. After transplantation there was a recurrence of the haemolytic uremic syndrome, with temporary worsening of the graft. Six months later there was a definite loss of graft and return to dialysis treatment. On April 2010 a severe systemic calciphylaxis related to secondary hyperparathyroidism was diagnosed. The patient underwent parathyroidectomy but, because of the unimproved clinical picture, treatment with sodium thiosulphate was initiated. There was only improvement in cutaneous lesions. The worsening general clinical condition of the patient caused death due to general septic complications. Conclusions. The coexistence of haemolytic uremic syndrome and secondary hyperpathyroidism makes the prognosis poor and, in this case, therapy, which counteracts calcium crystals precipitation, has no effect. Preventive parathyroidectomy can be considered as the only possible treatment

Ileus nakon spontanog intramuralnog hematoma jejunuma: prikaz slučaja i pregled literature

Anticoagulant therapy may cause the onset of a spontaneous intramural hematoma of the small bowel, in the jejunum, ileum or duodenum. A 53-year-old woman on therapy with heparin for previous pulmonary embolism was admitted for abdominal pain and vomit. Computed tomography scan visualized an intramural hematoma of the jejunum causing subtotal obstruction of the intestinal lumen. The patient underwent resection of a part of the jejunum, securing intestinal continuity by a mechanical side-to-side anastomosis. The postoperative course was regular, but the initial anticoagulant therapy was reduced to prevent recurrence. In conclusion, spontaneous hematoma of small bowel can occur as a complication of anticoagulant therapy. The clinical picture and rapid diagnosis indicate medical or surgical therapy.Antikoagulantna terapija može uzrokovati spontanu pojavu intraparijetalnog hematoma tankog crijeva na razini jejunuma, ileuma ili duodenuma. Prikazuje se klinički slučaj 53-godišnje žene na terapiji heparinom zbog ranije plućne embolije, koja je zadržana na bolničkom liječenju zbog bolova u trbuhu i mučnine. Tomografija abdomena potvrdila je prisutnost intraparijetalnog hematoma jejunuma koji je uzrokovao gotovo potpuno zakrčenje crijevnog lumena. Izvedena je resekcija zahvaćenog dijela jejunuma i rekonstrukcija crijevnog nastavka posredstvom “mehaničke latero-lateralne anastomoze”. Poslijeoperacijski tijek je bio uredan, ali je smanjena početna antikoagulantna terapija kako bi se izbjegao recidiv bolesti. U zaključku, spontani intraparijetalni hematom tankog crijeva može biti rezultat komplikacija antikoagulantne terapije. Klinička slika i brzo postavljanje dijagnoze upućuju na medicinsku ili kiruršku terapiju