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Renal System (renal + system)
Selected AbstractsEvaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imagingNMR IN BIOMEDICINE, Issue 1 2006Sander Langereis Abstract Different generations of Gd(III)DTPA-terminated poly(propylene imine) dendrimers {G1 [n,=,4 Gd(III) ions per molecule], G3 (n,=,16) and G5 (n,=,64)} and reference Gd(III)DTPA complex [G0 (n,=,1)] were characterized in terms of (i) longitudinal (r1) and transverse (r2) relaxivities in mouse blood plasma, (ii) concentration detection limits in vitro and (iii) in vivo contrast-enhanced MR imaging (CE-MRI) in mice at 1.5,,,T. Serial and dynamic CE-MRI were performed to monitor the distribution of MRI contrast agent in the heart, arteries, renal system, liver, spleen, bladder and tumor periphery. The relaxivities increased non-linearly with molecular weight (for G0 ionic r1,=,8.1,mM,1,s,1 and ionic r2,=,8.6,mM,1,s,1 to G5 19.3 and 25.0, respectively). The minimal detectable dendrimer concentration was more than two orders of magnitude lower for G5 (8.1,×,10,8,M) than for G0 (3.1,×,10,5,M). Sub-millimeter-sized blood vessels were well visualized with serial CE-MRI with each contrast agent. Dynamic CE-MRI showed timely renal clearance for all contrast agents, but a stronger and a prolonged blood signal enhancement for the higher generations of the dendritic contrast agent. Moreover, G0 and G1 showed a rapid tumor wash-in and wash-out, whereas G3 and G5 displayed a more gradual and prolonged tumor wash-in. In conclusion, both G0 and dendritic contrast agents G1, G3 and G5 are well suited for non-tissue-specific MRI of sub-millimeter-sized blood vessels and evaluating tumor microcirculatory characteristics in mice. Higher generations of dendritic contrast agents display lower concentration detection limits, which suggests their future use for molecular imaging. Copyright © 2006 John Wiley & Sons, Ltd. [source] Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseasesPATHOLOGY INTERNATIONAL, Issue 7 2010Takayuki Shiomi Cellular functions within tissues are strictly regulated by the tissue microenvironment which comprises extracellular matrix and extracellular matrix-deposited factors such as growth factors, cytokines and chemokines. These molecules are metabolized by matrix metalloproteinases (MMP), a disintegrin and metalloproteinases (ADAM) and ADAM with thrombospondin motifs (ADAMTS), which are members of the metzincin superfamily. They function in various pathological conditions of both neoplastic and non-neoplastic diseases by digesting different substrates under the control of tissue inhibitors of metalloproteinases (TIMP) and reversion-inducing, cysteine-rich protein with Kazal motifs (RECK). In neoplastic diseases MMP play a central role in cancer cell invasion and metastases, and ADAM are also important to cancer cell proliferation and progression through the metabolism of growth factors and their receptors. Numerous papers have described the involvement of these metalloproteinases in non-neoplastic diseases in nearly every organ. In contrast to the numerous review articles on their roles in cancer cell proliferation and progression, there are very few articles discussing non-neoplastic diseases. This review therefore will focus on the properties of MMP, ADAM and ADAMTS and their implications for non-neoplastic diseases of the cardiovascular system, respiratory system, central nervous system, digestive system, renal system, wound healing and infection, and joints and muscular system. [source] Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: Findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Ellen M. Ginzler Objective To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis. Methods Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5,1.0 gm/m2/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables. Results Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA,SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti,double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide. Conclusion In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis. [source] Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevisDEVELOPMENTAL DYNAMICS, Issue 1 2008Christina M. Bracken Abstract The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular behaviors throughout development. Previous studies implicated an important role for BMP signaling during the differentiation of the definitive mammalian kidney, the metanephros. In order to examine whether BMP signaling also plays an important role during the patterning of earlier renal systems, we examined the development of the earliest nephric system, the pronephros. Using the amphibian model system Xenopus laevis, in combination with reagents designed to inhibit BMP signaling during specific stages of nephric development, we revealed an evolutionarily conserved role for this signaling pathway during renal morphogenesis. Our results demonstrate that conditional BMP inhibition after specification of the pronephric anlagen is completed, but prior to the onset of morphogenesis and differentiation of renal tissues, results in the severe malformation of both the pronephric duct and tubules. Importantly, the effects of BMP signaling on the developing nephron during this developmental window are specific, only affecting the developing duct and tubules, but not the glomus. These data, combined with previous studies examining metanephric development in mice, provide further support that BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct. Developmental Dynamics 237:132,144, 2008. © 2007 Wiley-Liss, Inc. [source] Epidemiology of post-injury multiple organ failure in an Australian trauma systemANZ JOURNAL OF SURGERY, Issue 6 2009David C. Dewar Abstract Background:, The epidemiology of post-injury multiple organ failure (MOF) is reported internationally to have gone through changes over the last 15 years. The purpose of this study is to describe the epidemiology of post-injury MOF in Australia. Methods:, A 12-month prospective epidemiological study was performed at the John Hunter Hospital (Level-1 Trauma Centre). Demographics, injury severity (ISS), physiological parameters, MOF status and outcome data were prospectively collected on all trauma patients who met inclusion criteria (ICU admission; ISS > 15; age > 18, head Abbreviated Injury Scale (AIS) <3 and survival >48 h). MOF was prospectively defined by the Denver MOF score greater than 3 points. Data are presented as % or Mean+/,SEM. Univariate statistical comparison was performed (Student t -test, X2 test), P < 0.05 was considered significant. Results:, Twenty-nine patients met inclusion criteria (Age 40+/,4, ISS 29+/,3, Male 62%), five patients developed MOF. The incidence of MOF among trauma patients admitted to ICU was 2% (5/204) and 17% (5/29) in the high-risk cohort. The maximum average MOF score was 6.3 +/,1, with the average duration of MOF 5+/,2 days. Two patients had respiratory and cardiac failure, two patients had failure of respiratory, cardiac and hepatic systems, while one patient had failure of respiratory, hepatic and renal systems. One MOF patient died, all non MOF patients survived. MOF patients had longer ICU stays (20+/,4 versus 7+/,0.8 P= 0.01), tended to be older (60+/,11 versus 35+/,4 p=0.07). None of the previously described independent predictors (ISS, base deficit, lactate, transfusions) were different when the MOF patients were compared with the non-MOF patients. Conclusion:, The incidence of MOF in Australia is consistent with the international data. In Australia MOF continues to cause significant late mortality and morbidity in trauma patients. MOF patients have longer ICU stay than high-risk non MOF patients, and use significant resources. Our preliminary data challenges the timeliness of the 10-year-old independent predictors of post-injury MOF. The epidemiology, the clinical presentation and the independent predictors of post-injury MOF require larger scale reassessment for the Australian context. [source] | ||||||||||