244 research outputs found
REGRESSION OF NEUROPHYSIOLOGICAL ABNORMALITIES IN EXPERIMENTAL DIABETES AFTER ISLET TRANSPLANTATION
Regression of neurophysiological abnormalities in experimental diabetes after islet transplantation
Autori
F Purrello, V Caltabiano, M Vetri, C DEGANO, E VALLE, G POZZESSERE, S MORANO, G PUGLIESE, M SENSI, U DIMARIO
Data pubblicazione
1994/8/1
Conferenza
Diabetologia
Volume
37
Pagine
A217-A21
Effect of metformin on insulin binding to receptors in cultured human lymphocytes and cancer cells.
Effects of biguanides and sulfonylureas on insulin receptors in cultured cells
The effects of the two groups of oral agents on insulin receptors were studied in several types of cells in tissue culture: MCF-7 human breast cancer cells, IM-9 human lymphocytes, human fibroblasts, and H-35 rat hepatoma cells. In none of these cells did the four sulfonylureas tested, tolbutamide, glibenclamide (glyburide), gliclazide, and glisolamide, have any significant effects on insulin binding to its receptor. In contrast the two biguanides tested, phenformin and metformin, increased insulin binding in all cell types by 44 to 101%. These studies raise the possibility, therefore, that biguanides may have a direct effect on insulin receptors and this effect may account for the known effects of biguanides to lower elevated blood sugar levels in diabetic patients
Glial fibrillary acid protein (GFAP) and vimentin (VIM) expression in Astrocyte cultures pre-treated or/and treated with growth factors and glucocorticoids
dltA overexpression: A strain-independent keystone of daptomycin resistance in methicillin-resistant Staphylococcus aureus
The mechanisms leading to reduced susceptibility to daptomycin (DAP) are multifactorial and have not been fully elucidated. We analysed, by sequencing and expression studies, the role of the major molecular targets (cell-envelope charge genes, dltA, mprF, cls2; cell-wall turnover and autolysis genes, sceD, atl) involved in the emergence of DAP resistance in three series of isogenic clinical methicillin-resistant Staphylococcus aureus (MRSA) in which DAP resistance emerged after a heterogeneous glycopeptide-intermediate S. aureus (hGISA) step under teicoplanin and DAP therapy. All of the isolates had different genotypes and were delta-haemolysin negative, reflecting a strain proclivity to acquire DAP/glycopeptide non-susceptibility under antibiotic pressure. DAP exposure led to the emergence of DAP resistance after an hGISA step probably in parallel with the timing of the two antimicrobial administrations and, in two of three cases, in conditions of DAP underdosage. Real-time qPCR data revealed that all DAP-resistant (DAP-R) isolates had dltA overexpression, whereas mprF upregulation was found only in DAP-R strains with the S295L and T345I amino acid substitutions. Strains that were heteroresistant to DAP did not possess DAP-R-like characteristics. DAP-R strains presented high cls2 expression and no known cls2 mutations, and moreover exhibited sceD and atl upregulation. In conclusion, these findings highlight that dltA overexpression is the common pathway of resistance among genotypically different series of isolates and may represent the keystone of DAP resistance in MRSA, leading to electrostatic repulsion and, indirectly, to a reduction of autolysin activity. mprF mutations related to increased transcription may play a role in this complex phenomeno
Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour
Soft and flexible nanogels, produced by electron beam (e-beam) irradiation of poly(N-vinyl pyrrolidone) and acrylic acid, were evaluated as delivery devices of the inhibitor of miR-31, a small RNA molecule with an important role in colorectal cancer (CRC) progression. The nanogel carriers developed possess both carboxyl and primary amino groups; the former were activated to react with the primary amino group present in the purposely-functionalised AntimiR-31. Very high conjugation reaction yields were attained, as well as a remarkable colloidal and storage stability of the conjugates. The ability of these nanoconstructs to be internalized by cells and the specific interaction of conjugated AntimiR with its biological target, without being detached from the nanogel, was demonstrated in vitro. These results are a strong encouragement to further proceed in the pre-clinical evaluation of the therapeutic effects of these formulations in CRC
Early, but not advanced, glomerulopathy is reversed by pancreatic islet transplants in experimental diabetic rats: correlation with glomerular extracellular matrix mRNA levels
Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy
Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols
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