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 fo…

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 o…

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 ot…

A Good Breath of Oxygen for Beta-Like Cells Obtained From Porcine Exocrine Pancreatic Tissue

Ischemia is the most important factor that affects organ survival during harvesting. The two-layer method (TLM) is one of several cold storage solutions that seeks to preserve organs and cells avoiding in vivo and in vitro ischemia. We compared the retrieval of beta-like elements from exocrine pancreatic cells using TLM versus University of Wisconsin (UW) solutions. For this purpose pancreata laparoscopically harvested from 20 female pigs were preserved in UW solution or TLM before digestion. The resulting exocrine cells were divided into 2 groups: the first was cultured in a designed medium to allow differentiation into beta-like cells and the second was cryopreserved before the differenti…

Characterization of transfected HT-29 cells expressing the oncogenic Ras isoform KrasG13D.

Point mutations in codon 12 and 13 of K-ras are frequently found in DNA of colorectal cancer. It has been suggested that particular mutations at these sites may be associated with specific tumour phenotypes. To shed light on the molecular mechanisms on which depends this specificity we set up a system of HT-29 cells stably transfected with a cDNA coding for K-rasG13D under the control of an inducible promoter. Proliferation assay performed on one of the positives clones, showed a decreased growth rate in response to K-rasG13D expression and preliminary gene expression analysis showed an up-regulation of the cell-cycle inhibitor p21 WAF1.

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 t…

Pancreatic islets from non-heart beating donor pig: Two-layer preservation method in an in vitro porcine model

Purpose Pancreata from non-heart beating donors could represent an unlimited source of islets if their cell viability can be efficiently preserved during the time necessary to process the organs by the use of a better solution of preservation compared to the classic University of Wisconsin solution. The aim of this study was to determine whether it is possible to obtain functioning “alive islets” from non-heart-beating donors by comparing, on a porcine model, the classic “UW ice-store” method with a two-layer cold storage method (TLM) using oxygenated Perfluorocarbons (PFC) and UW. Methods Whole pancreata were harvested from 20 NHBDs female pigs with similar characteristics and preserved fo…

Abnormal expansion of segmented filamentous bacteria in the gut

Human intestinal microbiota create a complex polymicrobial ecology characterized by high population density, wide diversity, and complexity of interactions. Any imbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequences including an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract, which is referred to as small intestinal bacterial overgrowth (SIBO) syndrome. SIBO is frequently found in persons fulfilling criteria for irritable bowel syndrome (IBS), and the large overlapping of symptoms of these two pathological conditions led some authors to believe that IBS is secondary to S…

Intrachromosomal recombination of the c-myc locus leading to gene amplification

Possible relation between genetic recombination and amplification within the c-myc locus in a case of primary colorectal carcinoma

NUTRITION IN IBD PATIENTS

Inflammatory Bowel Disease (IBD) is a chronic disorder characterized by a relapsing-remitting course, which alternates between active and quiescent states, ultimately impairing a patients' quality of life.The two main types of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). CD Shows a transmural granulomatous inflammation that can involve any segment of the intestine affecting all layers of the intestinal wall, while UC is limited to the mucosa and superficial submucosa of the colon. In physiological conditions the gut is costantly exposed to various antigens, commensal microflora and pathogens and the inflammatory response is finely balanced. Anyhow i some individuals with geneti…

Gene expression profiling of HT-29 cells in response to induction of oncogenic H and K-ras.

DUE DIFFERENTI MECCANISMI MOLECOLARI COINVOLTI NEL FENOMENO DELL'AMPLIFICAZIONE GENICA IN UN CASO DI CARCINOMA COLORETTALE

Histologic effects of university of wisconsin two-layer method preservation of rat pancreas.

Marginal donors represent a poorly utilized source of organs for transplantation despite their availability. The key is to reduce the ischemic damage in the effort to improve organ quality. This study investigated the histologic effects after in situ perfusion of preservation with a two-layer method compared with the classic University of Wisconsin preservation in term of tissue integrity and number of viable exocrine cells in the rat pancreas both after exsanguination and at 8 weeks of cryopreservation. Pancreata harvested from 60 rats were collected using 3 methods: two-layer method following University of Wisconsin perfusion; exsanguination; and classic University of Wisconsin perfusion/…

Eight-point compass rose underlay technique in 72 consecutive elderly patients with large incisional hernia

Summary Background Repair 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. Methods A 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 t…

Intrachromosomal recombination of c-myc locus leading to gene amplification

A case of renal carcinoma metastasis simulating a thyroid goiter

Background: Although the thyroid is a highly vascularized gland, it is not a common target of metastasis from extrathyroidal cancer. Clear-cell renal carcinoma (cRCC) frequently metastasizes to the thyroid, representing 2-3% of all adult tumors, and more than 40% of patients present with metastases at diagnosis. The presence of cRCC thyroidal metastases makes the differential diagnosis from thyroid clearcell carcinoma extremely difficult. Patients and Methods: A 70-year-old woman presented with a mild compressive symptomatology due to a recent multinodular thyroid goiter with a ‘simple’ multinodular ultrasound pattern, in the absence of signs of malignancy and with normal findings for hormo…

From gut microflora imbalance to mycobacteria infection: is there a relationship with chronic intestinal inflammatory diseases?

The gut of a healthy adult harbours a myriad of different microbial species. It is estimated that approximately 10 14 are present in total bacterial colony forming units (CFU). Each colony colonizes a specific intestinal tract. In healthy adult, the main control of intestinal bacterial colonization occurs through gastric acidity but also other factors can influence the intestinal microenvironment such as pH, temperature, competition among different bacterial strains, peristalsis, drugs, radiotherapy and much more. Impaired microbial homeostasis leads to an alteration of the permeability of tissue, together with the activation of the intestinal immune system MALT (mucosal associated lymphoid…

POSSIBLE RELATION BETWEEN GUT MICROFLORA COMPOSITION AND ONCOGENIC RISK: IS STIMULATION OF INFLAMMATION THE ONE RING OF CONNECTION?

Human intestinalmicrobiotais characterizedby highpopulationdensity, wide diversity and complexity of interactions. Dysbiosis, both qualitative and quantitative, might have serious health consequences including an increase in the number and/or alteration of bacteria colonizing the gastrointestinal tract, which could be referred as gut microflora imbalance (GMI). GMI is frequently found in patients suffering from irritable bowel syndrome; this is the reason why some authors believe that IBS is secondary to GMI. Interestingly, GMI is also found in about 25% of Crohn’s disease patients. Stimulation of inflammation by the ‘dangerous bacteria’, through specific activation of the intestinal immune…

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?

Abstract 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 lea…

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…

Ileus following spontaneous jejunum intramural hematoma: case report and review of the literature.

Anticoagulant therapy may cause the onset of a spontaneous intramural hema- toma 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 hema- toma of small bowel can occur as a compli…

Struma ovarii. Case report and revision of the literature

Struma ovarii is a rare form of ovarian neoplasm, entirely or predominantly composed of thyroid tissue. This tumour generally has a benign biological behavior, although some cases of malignant transformation have been reported (5-10%). The tumour usually presents as an asymptomatic mature mass that may measure as much as 10 cm in diameter. The presence of ascites is possible (15-20%), and in a few cases the association of ascites and hydrothorax has been recorded (Pseudo-Meigs Syndrome); a close relationship between ascites and high levels of Ca-125, that may wrongly induce to a diagnosis of ovarian carcinoma is present. Other possible clinical consequences are compressive symptoms on adjac…

Two distinct amplification events of the c-myc locus in a colorectal tumour.

Southern hybridisation of genomic DNA extracted from a human primary colorectal carcinoma revealed amplification of a fragment containing the wild-type c-myc locus. Two additional rearranged DNA fragments, lying upstream of c-myc, fused to distant non-contiguous sequences from the same chromosome, with an opposite configuration (head to head vs. head to tail), were also found to be amplified. Sequences analysis suggested that these rearrangements resulted from illegitimate recombination at two distinct points within the DNA sequence just upstream of the c-myc ORF and further that these events triggered two different amplification mechanisms, only one of which, involving a strand invasion ev…

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is…

Double Endocrine Neoplasia in a Renal Transplant Recipient: Case Report and Review of the Literature

Abstract Introduction The incidence of cancer compared for age groups is 3–4 times higher in transplant recipients than the general population. The increased risk is related to immunosuppressive therapy as well as the use of increasingly older donors and recipients. Although cardiovascular disease with a functioning transplant is the leading cause of death (47%), cancer mortality is significant especially among older patients. However, the most frequent posttransplantation cancers relate to hemolymphopoietic organs and skin, whereas the occurrence of solid tumors elsewhere is rare. Herein we have described a rare case of synchronous double malignancy of endocrine organs (thyroid-adrenal) in…

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…

Sistemic calciphylaxis and thrombotic microangiopathy in a kidney transplant patient: Two mixing fatal syndromes?

Abstract Abnormalities in calcium and phosphorus metabolism are common and metabolic bone diseases develop often in patients with chronic renal failure (CRF). Effective clinical management includes measures to control phosphorus retention and prevent hyperphosphataemia, to maintain serum calcium concentrations within the normal range and to prevent excess parathyroid hormone (PTH) secretion by the judicious use of vitamin D sterols. Certain of these interventions, however, appear to increase the risk of soft tissue and vascular calcification in patients with End Stage Renal Disease (ESRD), so current therapeutic approaches are thus being re-evaluated in an effort to limit these risks. Patie…

GRANULOMATOUS MASTITIS DURING CHRONIC ANTIDEPRESSANT THERAPY: IS IT POSSIBLE A CONSERVATIVE THERAPEUTIC APPROACH?

Granulomatous mastitis is a rare benign inflammatory disease of the breast with multiple etiologies such as tuberculosis, sarcoidosis, foreign body reaction, and mycotic and parasitic infections. In contrast, idiopathic granulomatous mastitis (IGM) is characterized by the presence of chronic granulomatous lobulitis in the absence of an obvious etiology. Clinically and radiologically it may mimic breast carcinoma and so awareness of surgeons, pathologists, and radiologists is essential to avoid unnecessary mastectomies. Cases of IGM are reported during antidepressant therapy in patients also showing high levels of prolactinemia. In these cases, we believe that surgical excision must be avoid…

AMPLIFICAZIONE E RIARRANGIAMENTO NEI TUMORI COLORETTALI

Post-transplantation tertiary hyperparathyroidism.

Tertiary hyperparathyroidism is intended as a state of excessive autonomous excretion of parathyroid hormone after longstanding secondary hyperparathyroidism. It is a condition of a severe hyperparathyroidism that persists in the renal recipient despite a successful transplantation. The high levels of parathyroid hormone lead to a worsening of graft function accompanied by systemic symptoms. This article reviews the main aspects related to tertiary hyperparathyroidism from mechanism of pathogenesis to prevention and treatment, suggesting some indications about the best management of patients on a waiting list for kidney transplant.

Ileus Following Spontaneous Jejunum Intramural Hematoma: Case Report and Review of the 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 complicati…