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R Calafiore

Publications and source records attributed to R Calafiore.

52 records · Page 3Linked to original sources
PubMed1982

Erythrocyte concentration of glycolytic phosphorylated intermediates and adenosine nucleotides in subjects with diabetes mellitus.

We determined erythrocyte concentration of phosphorylated glycolytic intermediates and adenosine nucleotides in 9 non-ketotic diabetics under different conditions of glycemic control. We showed a significant increase of G6P, F6P and FDP levels in the 9 diabetics with poor glycemic control, whereas other phosphorylated glycolytic intermediates were in the normal range. After achieving fair glycemic control G6P, F6P and FDP fell to normal value. G6P, F6P and FDP were well correlated with simultaneously determined plasma glucose. Another 5 diabetics with poor glycemic control were connected to Biostator in order to determine the time relationship between blood glucose and erythrocyte levels of G6P, F6P and FDP. We demonstrated a prompt decrease to the normal values of the phosphorylated glycolytic intermediates where blood glucose fell to normal 60-90 minutes after automatic insulin delivery. Finally, we determined RBC glycolytic intermediates in 5 subjects with normal OGTT and in 5 subjects with normal fasting plasma glucose but abnormal OGTT. In this group we observed a prompt and persistent increase of G6P, F6P and FDP levels over the three hours hyperglycemia phase which has been induced by glucose load. No significant increase was found in subjects with normal OGTT. Our results demonstrate that erythrocyte glycolytic metabolism in abnormal in diabetics, depending strictly on the degree of glycemic control.

Adenine Nucleotides↗
PubMedDate not supplied

RNA expression bcl-w, a new related protein Bcl-2 family, and caspase-3 in isolated sertoli cells from pre-pubertal rat testes.

Apoptosis has a major role in molding the embryo, in the maintenance of tissue homeostasis, and in the defense against pathogens, while its disgregulation is strongly implicated in cancer as well as in autoimmune and degenerative diseases. The opposite action of anti-apoptotic proteins (Bcl-2 family) and pro-apoptotic proteins (p53, Bax, Bak) regulates the activation of caspases that are the effectors proteases of the cell suicide. Bcl-W is a pro-survival protein, recently discovered, related to the Bcl-2 family. The presence of Bcl-W is fundamental for spermatogenesis in rats. Caspases are cysteine-dependent aspartate-specific proteases, and their over-expression can result in apoptotic cell death. Normally, caspases exist in cells as inactive pro-enzymes and can be activated by 2 distinct mechanisms: the FADD/caspase 8 cascade, and the Apaf-1/caspase 9 cascade. These 2 mechanisms are used extensively by cells for the activation of the effectors caspases: caspase 3, caspase 6, and/or caspase 7. Bcl-W and caspases might have a pivotal role in maintenance of Sertoli cells integrity. In this study, we demonstrate that both Bcl-W mRNA and caspase 3 mRNA are expressed in isolated Sertoli cells of pre-puberal rat testes. This finding might be crucial in clarifying whether Sertoli cells die by an apoptotic mechanism. Further studies are required to understand whether the expression of Bcl-W and caspases is different before and after puberty in rat testis and/or in pathological conditions, that lead to an increased cell apoptosis.

Animals↗
PubMedDate not supplied

Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys.

Neonatal porcine islets within alginate microcapsules transplanted intraperitoneally (IP) or within semi-permeable macrocapsules (TheraCyte) and transplanted subcutaneously (SC) survive and reverse diabetes for up to 16 weeks in diabetic autoimmune nonobese diabetic (NOD) mice. The islets in microcapsules transplanted IP into nondiabetic cynomolgus monkeys survived for 8 weeks. Similar results were shown with islets transplanted in TheraCytes. Neither species showed adverse effects or evidence of infection with porcine endogenous retroviruses or other endemic pig viruses. Proof of principle is illustrated for successful xenotransplantation in humans.

Animals↗
PubMedDate not supplied

Short-term stimulation studies on neonatal pig pancreatic duct-derived cell monolayers.

Short-term stimulation with insulinotropic factors may induce morphologic and functional changes in primary ductal cell cultures as a potential source of stem cells. We sought to assess the capacity of hepatocyte growth factor (HGF) to induce expression and maturation of proteins--PDX-1 and GLUT-2--and the subsequent beta-cell secretory profiles. HGF, which is involved in pancreatic development, may induce islet beta-cell neogenesis. Primary ductal cell monolayers were cultured in Click's + FBS 10% at 37 degrees C until tissue confluence. The medium was enriched with HGF (10 ng/mL for different periods); controls were treated for similar times with normal culture medium. At the end of the study, three-dimensional islet-like cell aggregates were observed in both conditions. In all conditions immunostaining studies showed positivity for the major endocrine-phenotype cell markers: insulin, PDX-1, glucokinase, and GLUT-2. Furthermore, treatment with HGF for short periods induced the expression of a functionally active, phosphorylated isoform of PDX-1. Finally, we observed that under basal conditions the cells initially and progressively released proinsulin throughout 5 days in all settings. Thereafter proinsulin was gradually replaced by insulin in the culture medium, reflecting a maturation progress. This pattern of insulin maturation and release was more evident when the cells were continuously stimulated with HGF for 12 days. The employed stimuli seemed to differentiate the original ductal cell layers toward endocrine cell phenotypes that synthesize and release proinsulin and subsequently insulin. HGF seems to provide a more efficient differentiation.

Animals↗
PubMedDate not supplied

Transplantation of microencapsulated pancreatic human islets for therapy of diabetes mellitus. A preliminary report.

To circumvent immune destruction of pancreatic islet grafts, human islets were deposited, enveloped within algin-polyaminoacidic microcapsules, in artificial prostheses directly anastomosed to blood vessels. Three dogs and two patients with insulin-dependent diabetes received transplantations with microencapsulated human islets embodied in arterial or AV prosthesis bypasses without any pharmacologic immunosuppression. Graft function was documented in all recipients by significative production and sustenance of serum C-peptide levels, although insulin independence was consistently achieved in only one of three dogs and, transiently, in one of two patients. On retrieval of grafted prostheses, viable human islets were found in microcapsules, most of which were freely dispersed in the vascular chambers. Vascular prostheses may represent a suitable site of implantation for large numbers of human islets, immunoprotected in semipermeable and biocompatible microcapsules, and be a novel strategy for therapy of insulin-dependent diabetes mellitus (IDDM).

Animals↗
PubMedDate not supplied

Metformin potentiates B-cell response to high glucose: an in vitro study on isolated perfused pancreas from normal rats.

This study investigated the effects of metformin on pancreatic A-B- and D-cell functions using the isolated perfused rat pancreas model. The lactate output rate following metformin infusion was also monitored. Metformin was infused at the low "therapeutic" concentration of 1.5 micrograms/ml and its effects were evaluated in three different glycaemic conditions: during a basal infusion of 4.44 mM glucose, during a moderate increase to 8.88 mM of glucose concentration, and finally during a higher 16.66 mM glycaemic stimulus. Basal insulin secretion and B-cell release during the lower hyperglycaemic stimulus were unaffected by metformin infusion. On the contrary, the drug significantly enhanced insulin response to 16.66 mM glucose, particularly by increasing the second phase of hormone release. Glucagon and somatostatin releases during metformin infusion were similar to the secretory pattern observed in the control experiments both in the basal condition and in the presence of the two different hyperglycaemic stimuli. Finally metformin did not modify the lactate output rate from perfused pancreas, irrespective of the different glycaemic conditions employed. Therefore our data suggest--at least in rats, in in vitro experiments but above all in the presence of markedly elevated hyperglycaemic conditions--that metformin may influence the glucose stimulatory effect on B-cell activity.

Animals↗