New insights into proteinuria/albuminuria.

The fractional clearance of proteins as measured in healthy human subjects increases 10,000-100,000- fold when studied in nephrotic patients. This remarkable increase cannot be accounted for by extracellular biophysical mechanisms centered at the glomerular filtration barrier. Rather, it is the nephron and its combination of filtration and cellular uptake that can provide a plausible explanation of these fractional clearance changes. The nephron has two regions that critically determine the level proteinuria/albuminuria. Glomerular filtration of plasma proteins is primarily a size selective event that is basically unchanged in acquired and genetic kidney disease. The glomerular concepts of 'charge selectivity' and of 'large pores', previously used to explain proteinuria, are now recognized to be flawed and non-existent. Filtered proteins then encounter downstream two protein receptors of the Park and Maack type associated with the proximal tubular cell. The high capacity receptor is thought to retrieve the majority of filtered proteins and return them to the blood supply. Inhibition/saturation of this pathway in kidney disease may create the nephrotic condition and hypoproteinemia/hypoalbuminemia. Inhibitors of this pathway (possibly podocyte derived) are still to be identified. A relatively small proportion of the filtered protein is directed towards a high affinity, low capacity receptor that guides the protein to undergo lysosomal degradation. Proteinuria in normoproteinemic states is derived by inhibition of this pathway, such as in diabetes. The combination of glomerular sieving, and the degradation and retrieval pathways can quantitatively account for the changes in fractional clearance of proteins in the nephrotic condition. Finally, the general retrieval of filtered protein by the proximal tubular cell focuses on the teleological importance of this cell as this retrieval represents the third pillar of retrieval that this cell participates in (it also retrieves water and salt).

Inhibition of the metabolic degradation of filtered albumin is a major determinant of albuminuria.

Inhibition of the degradation of filtered albumin has been proposed as a widespread, benign form of albuminuria. There have however been recent reports that radiolabeled albumin fragments in urine are not exclusively generated by the kidney and that in albuminuric states albumin fragment excretion is not inhibited. In order to resolve this controversy we have examined the fate of various radiolabeled low molecular weight protein degradation products (LMWDPs) introduced into the circulation in rats. The influence of puromycin aminonucleoside nephrosis on the processing and excretion of LMWDPs is also examined. The status and destinies of radiolabeled LMWDPs in the circulation are complex. A major finding is that LMWDPs are rapidly eliminated from the circulation (>97% in 2 h) but only small quantities (<4%) are excreted in urine. Small (<4%) but significant amounts of LMWDPs may have prolonged elimination (>24 h) due to binding to high molecular weight components in the circulation. If LMWDPs of albumin seen in the urine are produced by extra renal degradation it would require the degradation to far exceed the known catabolic rate of albumin. Alternatively, if an estimate of the role of extra renal degradation is made from the limit of detection of LMWDPs in plasma, then extra renal degradation would only contribute <1% of the total excretion of LMWDPs of albumin. We confirm that the degradation process for albumin is specifically associated with filtered albumin and this is inhibited in albuminuric states. This inhibition is also the primary determinant of the massive change in intact albuminuria in nephrotic states.

Do large pores in the glomerular capillary wall account for albuminuria in nephrotic states?

Albuminuria in nephrotic states is thought to arise from the formation of large pores in the glomerular capillary wall as large hydrodynamic probes, like Ficoll, have increased fractional clearance. In the present study, we tested for large pore formation in a novel manner. We accounted for the rates of plasma elimination as determined for tritium-labeled tracers of uncharged polydisperse Ficoll (radii range: 35-85 Å) and two globular (14)C-labeled proteins, albumin (radius: 36 Å) and IgG (radius: 55 Å), in control and puromycin aminonucleoside nephrotic (PAN) Sprague-Dawley rats. The plasma elimination rates were then matched to the urinary excretion of these labeled materials (n = 7). Albumin and IgG plasma retention rates were identical and far enhanced compared with the retention rates of inert transport markers of equivalent hydrodynamic radius; their elimination rate corresponded to the elimination of a 75-Å radius Ficoll (n = 5) and >105-Å radius dextran (n = 5). In PAN, they were eliminated as ∼36- and ∼55-Å radii Ficoll, respectively, equivalent to their hydrodynamic radii. In contrast, there was no comparable increase in the elimination rate of Ficoll in PAN. The total plasma clearance of Ficoll in control and PAN rats and the urinary clearance in PAN rats were essentially the same for all radii. On the other hand, the urinary clearance of >45-Å radii Ficoll in controls was considerably lower with increasing radii, demonstrating a postfiltration cellular uptake in controls, which, when inhibited in nephrotic states, would account for apparent large pore formation.

Testing the educational potential of 3D visualization software in oral radiographic interpretation.

There is heightened optimism about the potential of 3D visualization software as an alternative learning resource in radiology education. The purpose of this study was to investigate the effect of 3D visualization software on students' learning of oral radiographic interpretation from 2D radiographic images. Fourth-year dental students underwent a learning intervention phase of radiographic interpretation of oral pathoses using 3D visualization software. The success of the educational intervention was assessed by quantitative means, using a radiographic interpretation test, and by qualitative means, using a structured Likert-scale survey, asking students to evaluate their own learning outcomes. It was anticipated that training with the rotational mode of 3D visualization software would provide additional depth cues, enabling students to create spatial-mental models of anatomy that they can apply to 2D radiographic interpretation of oral pathoses. Although quantitative assessment did not support this, questionnaire evaluations demonstrated a positive effect of the 3D visualization software by enhancing students' learning about radiographic interpretation. Despite much optimism about the educational potential of 3D visualization software, it is important to understand the interactions between learners and such new technologies in order to identify potential advantages and limitations prior to embracing them as learning resources.

Canine transmigration: comprehensive literature review and report of 4 new Australian cases.

Canine transmigration is a rare dental anomaly unique to the mandibular arch, involving intraosseous migration of the unerupted tooth across the midline. Currently, there is a lack of consensus on the definition of transmigration. This report suggests a unified definition of transmigration, that being when a canine has crossed the midline by more than half its length. Numerous publications reporting mandibular canine transmigration therefore cannot be considered as being truly transmigrated. Here we undertake a comprehensive review of the literature, and report 4 new cases of transmigrated mandibular canines, 2 of which present with unique features. One case shows a vertically positioned transmigrated canine, whereas the other shows a horizontally transmigrated canine underlying an impacted canine. Furthermore, this cohort is the first to be reported in an Australian population.