Bruce Molitoris

..In summary, these results help explain the previously conflicting microscopy and micropuncture data describing albumin filtration and highlight the dynamic nature of glomerular albumin permeability...

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..Its use in the kidney is in its infancy but offers much promise for unraveling the complex interdependent physiologic and pathophysiologic processes known to contribute to cell function and disease...

..Its use in acute kidney injury is in its infancy but offers much promise for unraveling the complex interdependent processes known to contribute to cell injury and organ failure...

..We attempt to show how visual data can be quantified, thus allowing enhanced understanding of the process under study. Finally, emphasis is given to the possible future opportunities of this technology and its present limitations...

..Targeting siRNA to p53 leads to a dose-dependent attenuation of apoptotic signaling, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury...

..Great strides forward are being made in breaking down important barriers to the successful prevention and treatment of this devastating disorder...

..Therefore, measuring total renal blood flow may not permit an adequate understanding of the role of altered hemodynamics in septic patients who develop acute renal failure...

..These proposed standards will need to be validated in future studies, a process that will be facilitated by the Acute Kidney Injury Network, which offers a forum that encourages acquisition of knowledge to improve patient outcomes...

..Therefore, this approach compliments existing molecular, biochemical, and pharmacologic techniques by advancing data analysis and interpretation to subcellular levels for molecules without the requirement for fixation...

..Glomerular endothelial dysfunction may lead to preglomerular shunting of blood flow allowing kidney blood flow to remain close to normal while resulting in a reduction in glomerular filtration rate...

..Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs...

..New diagnostic and therapeutic approaches to ischemic ARF must incorporate these finding to devise early recognition strategies and therapeutic approaches...

..These data demonstrate XAC(wt)-GFP participates in ischemia-induced actin cytoskeletal alterations and determines the rate and extent of these ATP depletion-induced cellular alterations...

..This novel and simple method will permit the determination of indices of sensitivity and specificity for the TUNEL assay in other tissues and experimental conditions...

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..The Golgi complex must then endure the effects of gentamicin accumulated in larger quantities in an aberrant physiological state...

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..Together, these data support the argument that folate conjugates (and, by extrapolation, physiological folate) bind to the apical surface of proximal tubule cells and are transported into and across the cells in endocytic compartments...

..Further development and utilization of these techniques, especially in concert with genetic, proteomic, and molecular approaches, will allow for needed insights into the pathophysiology and therapy in human ARF...

..This approach also offers a high sensitivity for determining plasma clearance rate of a fluorescent compound. This feature is important for rapidly quantifying small differences in plasma clearance when kidney function is changing...

..Taken together, these data indicate that vascular dropout post-AKI results from endothelial phenotypic transition combined with an impaired regenerative capacity, which may contribute to progressive chronic kidney disease...

..These results suggest that one consequence of gentamicin exposure is disruption of Arf-dependent protein trafficking...

..However, its use in preclinical animal models offers new insight into physiologic processes and the pathophysiology and treatment of disease processes...

..We suggest that this disorganization of the actin cytoskeleton may play a contributory role in the loss of autoregulation of renal blood flow and the aberrant vascular reactivity in postischemic ARF...

..These results demonstrate the potential power of the GP imaging technique for quantitative studies of glomerular filtration and tubular reabsorption...

..Taken together, these findings indicate that renal vascular endothelial injury occurs in ischemic ARF and may play an important role in the pathophysiology of ischemic ARF...

..This mechanism provides a biochemical basis for the accumulation of F-actin aggregates in ischemic cells...

..This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF...

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..Cellular damage and inflammation after ischemia contribute to sustained acute renal failure (ARF)...

..By using an sTM variant, we also determined that the protective effects of sTM were independent of its ability to generate activated protein C. These data suggest that sTM may have therapeutic potential for ischemic AKI...

..In conclusion, in the early stages of diabetic nephropathy, the PT plays a major role in the development of albuminuria, which may be preceded by peptideuria...

..Also, recent advances in other imaging techniques offer potential clinical diagnostic tools to study acute kidney injury in animal models and in patients...

..23Na-MRI has great potential for noninvasive, clinical diagnosis of evolving ATN in the setup of acute renal failure and in differentiating ATN from other causes of renal failure where tubular function is maintained...

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..These studies have identified a component of the native gentamicin congener mixture that retains its bactericidal properties with minimal or no apparent nephrotoxicity...

..This study documents that renal ischemia induces dynamic changes in the molecular interactions between slit diaphragm proteins, leading to podocyte damage and proteinuria...

..Therefore, application of this technology will provide direct visualization of organ-specific and cell-specific responses to an array of stimuli and therapeutic approaches, enhancing our understanding and treatment of disease processes...

..These results strongly support the importance of cofilin regulation in ischemia-induced endothelial cell actin cytoskeleton alterations leading to cell damage and microvascular dysfunction...

..Furthermore, the data suggest a potential therapeutic role for APC in the treatment of ARF...

..These results suggest cytokines signal through the Rho-ROCK pathway, but also through another pathway to affect actin dynamics...

..Finally, up to three fluorophores can be visualized simultaneously allowing for three different or interactive processes to be observed and resolved...

..The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity...

..These results suggest that a combinatorial antiangiogenic gene therapy approach involving Ad-hEndo-angio and Ad-sTie2 could become a novel form of treatment for localized human prostate cancer...

..We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI...

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..There is also potential that a number of serum and urine bio-markers developed in preclinical studies and currently being investigated and validated, will enable the early diagnosis of AKI...

..Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis...

..The vital role of multi-disciplinary conferences for disseminating knowledge and clarifying issues in clinical practice was recognized...

..Those of older age, male gender, and black race are more likely to have ARF. These data show ARF to be a major contributor to morbidity and mortality in hospitalized patients...

..The techniques described here can be applied to study the integrated cell communication evoked by a variety of bacterial pathogens, assisting in the design of strategies to combat bacterial infections...

..By performing these studies, it is hoped that formulation of specific therapies to delay and/or inhibit this toxicity will become possible. ..

..The research development and support activities of the imaging facility are expected to provide numerous opportunities to impact the understanding of renal disease processes and therapeutic interventions. ..

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..These research development and support activities are expected to provide numerous opportunities to impact the understanding of renal physiology, disease processes and therapeutic interventions. ..