Over-expression of adenosine deaminase in mouse podocytes does not reverse puromycin aminonucleoside resistance

<p>Abstract</p> <p>Background</p> <p>Edema in nephrotic syndrome results from renal retention of sodium and alteration of the permeability properties of capillaries. Nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats reproduces the biological and clinical signs of the human disease, and has been widely used to identify the cellular mechanisms of sodium retention. Unfortunately, mice do not develop nephrotic syndrome in response to PAN, and we still lack a good mouse model of the disease in which the genetic tools necessary for further characterizing the pathophysiological pathway could be used. Mouse resistance to PAN has been attributed to a defect in glomerular adenosine deaminase (ADA), which metabolizes PAN. We therefore attempted to develop a mouse line sensitive to PAN through induction of normal adenosine metabolism in their podocytes.</p> <p>Methods</p> <p>A mouse line expressing functional ADA under the control of the podocyte-specific podocin promoter was generated by transgenesis. The effect of PAN on urinary excretion of sodium and proteins was compared in rats and in mice over-expressing ADA and in littermates.</p> <p>Results</p> <p>We confirmed that expression of ADA mRNAs was much lower in wild type mouse than in rat glomerulus. Transgenic mice expressed ADA specifically in the glomerulus, and their ADA activity was of the same order of magnitude as in rats. Nonetheless, ADA transgenic mice remained insensitive to PAN treatment in terms of both proteinuria and sodium retention.</p> <p>Conclusions</p> <p>Along with previous results, this study shows that adenosine deaminase is necessary but not sufficient to confer PAN sensitivity to podocytes. ADA transgenic mice could be used as a background strain for further transgenesis.</p

The challenge to verify ceramide's role of apoptosis induction in human cardiomyocytes - a pilot study

<p>Abstract</p> <p>Background</p> <p>Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to <it>ex vivo </it>conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed.</p> <p>Results</p> <p>In group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed.</p> <p>Conclusion</p> <p>Ceramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.</p

MRI to assess renal structure and function

Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease

Color analysis of different ceramic systems

PubMed ID: 20478787This study compared the color properties of three different ceramic systems. Three groups of 10 specimens each were prepared: Dental porcelain alloy was used as a framework for conventional and Probond metal-ceramic systems, while glass-ceramic ingots were used as a framework for 10 samples using an all-ceramic system. For the former, dentin porcelain was applied and a ceramic veneering material was applied to the ingot frameworks. Using a dental spectrophotometer, the pre- and post-glaze color compatibility between disc specimens and A3 shade was evaluated. The Kruskal-Wallis test was used to compare color differences among groups in this study, while the Mann-Whitney U test was used to make bilateral comparisons among the three different ceramic systems. The values obtained during the dentin stage revealed a significant difference in the all-ceramic group (p 0.05). These results suggest that Probond can yield esthetically superior results in clinical applications compared to conventional ceramic systems

The evaluation of the removal forces on the conus crowned telescopic prostheses with the finite element analysis (FEA)

WOS: 000179548100008PubMed ID: 12453261The removable partial dentures supported by the telescopic crowns are an alternative for directly retained removable partial dentures. The stress distribution on the retainers and the surrounding tissues created by the telescopic and conus crowns of different sizes ( 4, 5, 6 mm) and taper (0degrees, 2degrees, 4degrees, 6degrees) was investigated with the finite element analysis (FEA) method. The stress values obtained were evaluated either as strain or tensional forces. The loosening force of the secondary crown being determined as 5 N, the increase in tension of the dentine, metal structure, alveolar bone, periodontal ligament and the pulp were determined by the increasing height and taper. The reason for the increase in tensional forces with increasing taper was the result of the constant loosening force of 5 N applied in all experimental models. The strain was more effective than the tension with the highest stress being in the cervical region of the metal structure. The aim of this study was to determine the force exerted on the teeth and surrounding tissues by the loosened secondary crown