446 research outputs found
Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy
No full textUrinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including: inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may effect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: Docherty, Neil G.. Universidad de Dublin; IrlandaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentin
A gender comparison of postobstructive injury in the rat kidney
No full textBackground/Aims: Unilateral ureteral obstruction (UUO) results in renal injury. Studies report increased injury indices in male rats following UUO. Our study examined whether this gender-based renal response to UUO was reflected in sustained differences following relief of obstruction. Methods: Adult male/female rats (200-400 g) were subjected to either sham surgery (S/RN) or UUO (UUO/RN). At 24 h, obstruc- tion was relieved and all animals underwent contralateral nephrectomy. Five days after initial surgery, animals were placed in metabolic cages and given water ad libitum for 24 h followed by a 24-hour period of complete water restriction. On day 7, animals were euthanized and samples harvested. Tubular injury, urinary volume/osmolality, creatinine clearance, plasma arginine vasopressin, renal medullary V2 receptor and aquaporin 2 (AQP2) expression were measured. Results: Male UUO/RN rats showed increased renal apoptotic injury and reduced creatinine clearance rates (glomerular filtration rate) vs. females. No gender-dependent differences were observed in urinary osmolality or concentrating ability. AQP2 expression increased post-obstruction. Conclusion: Increased injury in males following UUO remains manifest during early recovery after release of obstruction. Despite this, the grade of postobstructive diuresis is not significantly altered between sexes. This may reflect reduced glomerular filtration rate and elevated AQP2 in male rats.Fil: Quinlan, Mark R.. The Conway Institute Of Biomolecular And Biomedical Science; Irlanda. University College Dublin; IrlandaFil: Cronin, Peter. University College Dublin; IrlandaFil: Daly, Padraig J.. University College Dublin; Irlanda. The Conway Institute Of Biomolecular And Biomedical Science; IrlandaFil: Watson, Ronald W. G.. The Conway Institute Of Biomolecular And Biomedical Science; Irlanda. University College Dublin; IrlandaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Docherty, Neil G.. Trinity College Dublin; IrlandaFil: Fitzpatrick, John M.. University College Dublin; Irlanda. The Conway Institute Of Biomolecular And Biomedical Science; Irlanda. Mater Misericordiae University Hospital; Irland
Engaging Asian faith communities and counselling psychology perspectives in the development of older adult services.
No full textA thesis submitted in fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor in Counselling Psychology.This mixed methods study investigates how counselling psychology perspectives can collaborate with the Sikh community in the development of Older Adult Psychology Services. 73 Sikh participants, aged 45-65 years contributed in English and Punjabi through interview, questionnaire or focus group at multiple community sites across 3 metropolitan boroughs in Sandwell. Qualitative data from validated scenarios and personal experience were analysed by a thematic approach informed by Interpretive Phenomenological Analysis. Master themes were identified for religion, quality of life and service development. The SF12v2 (Ware et al., 2005) is a measure of health and well-being which showed just below average population norms for physical and mental health components of well-being for the Sikh Community. The God Locus of Health Control Scale (Wallston et al., 1999) demonstrated religion‟s importance, and how karma is integral to Sikhs‟ understanding and management of health. 80.6% (N=31) prefer older adult service providers to account for their religious beliefs and counselling psychologists are recommended to address this request in their engagement with this community. Preferences in the modes of delivery, types of psychological intervention and aids to service uptake are provided with recommendations for clinical practice, training and future research
Transport strategy in Scotland since devolution
No full textThis article critically reviews how the Scottish Executive's approach to transport has developed since devolution. Although there is much to commend, a number of concerns can be identified, including the possibility that a number of strategic infrastructure schemes appear to have been approved on political rather than on technical grounds. It is difficult to know whether the current set of transport infrastructure investment plans represents good value for public money
Fibrinogen as a damage-associated mitogenic signal for the renal fibroblast
No full textFibroblast proliferation is central to the evolution of renal tubulointerstitial fibrosis. Using both in vivo and in vitro approaches, Sörensen et al. describe a role for fibrinogen as a cell-surface-receptor-mediated mitogen for renal fibroblasts. This interaction, likely to be initiated by injury and extravasation and to signal principally via Toll-like receptors, implicates fibrinogen in renal fibrosis beyond its textbook description as a scaffold precursor at the end of the coagulation cascade
Isolation and gene expression profiling of intestinal epithelial cells: crypt isolation by calcium chelation from in vivo samples
No full textAine Balfe,1,2 Grainne Lennon,1,2 Aonghus Lavelle,1,2 Neil G Docherty,1 J Calvin Coffey,3 Kieran Sheahan,4 Desmond C Winter,2 P Ronan O’Connell1,2 1School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, 2Centre for Colorectal Disease, St Vincent’s University Hospital Dublin, Dublin, 3Graduate Entry Medical School, University Hospital Limerick, 4i Centre for Interventions in Infection, Inflammation and Immunity, University of Limerick, Limerick, 4Histopathology Department, St. Vincent’s University Hospital Dublin, Dublin, Ireland Aim: The epithelial layer within the colon represents a physical barrier between the luminal contents and its underlying mucosa. It plays a pivotal role in mucosal homeostasis, and both tolerance and anti-pathogenic immune responses. Identifying signals of inflammation initiation and responses to stimuli from within the epithelial layer is critical to understanding the molecular pathways underlying disease pathology. This study validated a method to isolate and analyze epithelial populations, enabling investigations of epithelial function and response in a variety of disease setting. Materials and methods: Epithelial cells were isolated from whole mucosal biopsies harvested from healthy controls and patients with active ulcerative colitis by calcium chelation. The purity of isolated cells was assessed by flow cytometry. The expression profiles of a panel of epithelial functional genes were investigated by reverse transcription-polymerase chain reaction (PCR) in isolated epithelial cells and corresponding mucosal biopsies. The expression profiles of isolated cells and corresponding mucosal biopsies were evaluated and compared between healthy and inflamed colonic tissue. Results: Flow cytometry identified 97% of cells isolated as intestinal epithelial cells (IECs). Comparisons of gene expression profiles between the mucosal biopsies and isolated IECs demonstrated clear differences in the gene expression signatures. Sixty percent of the examined genes showed contrasting trends of expression between sample types. Conclusion: The calcium chelation isolation method provided a reliable method for the isolation of a pure population of cells with preservation of epithelial cell-specific gene expression. This demonstrates the importance of sample choice when investigating functions directly affecting the colonic epithelial layer. Keywords: epithelial cells, ulcerative colitis, gene expression, mucosal biopsies, molecular pathways, colonic inflammatio
Intestinal regulation of urinary sodium excretion and the pathophysiology of diabetic kidney disease: a focus on glucagon-like peptide 1 and dipeptidyl peptidase 4.
No full textThe tubular hypothesis of glomerular filtration and nephropathy in diabetes is a pathophysiological concept that assigns a critical role to the tubular system, including proximal tubular hyper-reabsorption and growth, which is relevant for early glomerular hyperfiltration and later chronic kidney disease. Here we focus on how harnessing the bioactivity of hormones released from the gut may ameliorate the early effects of diabetes on the kidney in part by attenuating proximal tubular hyper-reabsorption and growth. The endogenous tone of the glucagon-like peptide 1 (GLP-1)/GLP-1 receptor (GLP-1R) system and its pharmacological activation are nephroprotective in diabetes independent of changes in blood glucose. This is associated with suppression of increases in kidney weight and glomerular hyperfiltration, which may reflect, at least in part, its inhibitory effects on tubular hyper-reabsorption and growth. Inhibition of dipeptidyl peptidase 4 (DPP-4) is also nephroprotective independent of changes in blood glucose and involves GLP-1/GLP-1R-dependent and -independent mechanisms. The GLP-1R agonist exendin-4 induces natriuresis via activation of the GLP-1R. In contrast, DPP4 inhibition increases circulating GLP-1, but drives a GLP-1R-independent natriuretic response, implying a role for other DPP-4 substrates. The extent to which the intrarenal DPP-4/GLP-1 receptor system contributes to all these changes remains to be established, as does the direct impact of the system on renal inflammation
Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy
No full textThis is an open access article distributed under the Creative Commons Attribution License.Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.This study was supported by grants from Ministerio de Economía y Competitividad (Grant SAF2010-15881 and Red de Investigacion Cooperativa en Enfermedades Renales REDINREN RD12/0021/0032), Junta de Castilla y León (Grant SA 001/C05 and Excellence Group GR100), and REDINREN which is an initiative of the Instituto de Salud
Carlos III of Spain supported by FEDER funds. When performing the present study, Ana B. Rodríguez-Pena was a fellow of the Fundacion Renal “Iñigo Ávarez de Toledo” and Neil
G. Docherty was a fellow ofThe Marie Curie Programme, EU.Peer Reviewe
Phonology as Cognition
No full textThis paper attempts to ground phonology within psychology. That is, we are interested in phonology as a branch of the study of mental representation, the psychology of mind. In order to develop this `phonology of mind' we need to understand the relationship between formal properties of grammars and the `substance' which representations represent. Current trends in phonology fail to offer a coherent conception of form and substance and are also inconsistent with basic principles of science. In addition to critiquing the phonological literature on markedness and related issues, we offer a modest result in the study of the formal properties of the phonology: we demonstrate that phonology needs to make use of quantification to characterize the structural descriptions of rule and constraints.This is an extended version of the Linguistic Inquiry squib "Substance Abuse and Dysfunctionalism: Current Trends in Phonology" (2000). The definitive version of this paper was published in Phonological Knowledge: Conceptual and Empirical Issues (2000) and is available at http://ukcatalogue.oup.com/product/9780198241270.do#.Ul7HCGSgknV.Hale, M., & Reiss, C. (2000). Phonology as cognition. In N. Burton-Robert, P. Carr, & G. Docherty (Eds.) Phonological knowledge: Conceptual and empirical issues (pp. 161-184). New York: Oxford University Press.ISBN: 9780198241270 (Published book
Reconfiguration of the small intestine and diabetes remitting effects of Roux-en-Y gastric bypass surgery
No full textAlterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field
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