The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are found elevated in various conditions characterized by renal growth (e.g. diabetes mellitus, hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was administered alone or in combination with IGF-I to Snell dwarf mice, an in vivo model without compensatory feedback effects on growth hormone (GH) secretion. In three control groups of Snell dwarf mice, placebo, GH or IGF-I was administered. Compared with placebo, kidney weight increased in all treated groups, however, with different effects on kidney morphology. Administration of IGF-I, alone or in combination with IGFBP-1, tended to increase glomerular volume, while no changes were seen in the other groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation of the thin limbs of Henle's loop, while GH or IGF-I administration had no visible effect. Furthermore, IGF-I administration resulted in an increased mean number of nuclei per cortical area and renal weight, whereas GH, IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ hybridization and immunohistochemistry showed specific changes of the renal IGF system expression patterns in the different groups. Particularly, IGFBP-1 administration resulted in extensive changes in the mRNA expression of the renal IGF system, whereas the other administration regimen resulted in less prominent modifications. In contrast, administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes in the protein expression of the renal IGF system. Our results indicate that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on the renal tubular system that differ from the effects of IGF-I

The Right Place at the Right Time: Creative Spaces in Libraries

Purpose This essay explores the recent trend in libraries: that of the establishment of spaces specifically set aside for creative work. The rise of these dedicated creative spaces is owed to a confluence of factors that happen to be finding their expression together in recent years. This essay examines the history of these spaces and explores the factors that gave rise to them and will fuel them moving forward. Design/Methodology/Approach A viewpoint piece, this essay combines historical research and historical/comparative analyses to examine the ways by which libraries have supported creative work in the past and how they may continue to do so into the 21st century. Findings The key threads brought together include a societal recognition of the value of creativity and related skills and attributes; the philosophies, values, and missions of libraries in both their longstanding forms and in recent evolutions; the rise of participatory culture as a result of inexpensive technologies; improved means to build community and share results of efforts; and library experience and historical practice in matters related to creativity. The chapter concludes with advice for those interested in the establishment of such spaces, grounding those reflections in the author’s experiences in developing a new creative space at Virginia Commonwealth University. Originality/value While a number of pieces have been written that discuss the practicalities of developing certain kinds of creative spaces, very little has been written that situates these spaces in larger social and library professional contexts; this essay begins to fill that gap

Circulating levels of insulin-like growth factor-I (IGF-I) correlate with disease status in leprosy

<p>Abstract</p> <p>Background</p> <p>Caused by <it>Mycobacterium leprae </it>(ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems.</p> <p>Methods</p> <p>In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT), borderline lepromatous (NR BL), and lepromatous (NR LL) leprosy patients in addition to healthy controls (HC). LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α) were evaluated at diagnosis and during development of reversal (RR) or erythema nodosum leprosum (ENL) reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method.</p> <p>Results</p> <p>The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients) in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients). Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients. Interestingly, IGF-I behaved contrary to what was observed during RR episodes in R BL patients.</p> <p>Conclusions</p> <p>Our data revealed important alterations in the IGF system in relation to the status of the host immune-inflammatory response to ML while at the same time pointing to the circulating IGF-I/IGFBP-3 levels as possible predictive biomarkers for ENL in LL patients at diagnosis.</p

Isolation and expansion of cytokeratin positive progenitor cells from adult murine pancreatic ducts expressing Pdx-1, Nestin, Sox9, MafA and hepatic nuclear factors

BACKGROUND: Recent studies suggest that stem cells may represent a putative source for the generation of beta cells. However, the identity and characteristics of stem cells from adult pancreas and conditions for their large scale expansion are still poorly defined. METHODS: DPC were isolated from adult pancreatic ducts of C57BI/6 mice. Expression profile was investigated by PCR, FAGS and immunohistochemistry. RESULTS: DPC express a panel of stem cell associated markers such as Pdx-1, cytokeratin-19 (CK19), nestin, Sox9 together with the transcription factor MafA and hepatic nuclear factors HNF1 beta, HNF3 beta, HNF4 alpha and HNF6. This gene expression profile is suggesting that DPC might be a promising tool for endocrine diMrentiation. Atter stimulation with picolinic acid and hypoxia, DPC expressed the endocrine differentiation marker Ngn3. Nevertheless, insulin production was not observed. CONCLUSIONS: We here describe a protocol for the isolation end expansion of murine pancreatic ductal progenitor cells (DPC) displaying high self-renewal, spheroid-and colony-forming capacity. Further studies are required to elucidate the conditions for differentiation into mature pancreatic endocrine cell lineages