Biomedical subjects

Michael Fischereder

Publications and source records attributed to Michael Fischereder.

21 records · Page 2Linked to original sources

PubMedDate not supplied

Effects of aortic stenosis on renal renin, angiotensin receptor, endothelin and NOS gene expression in rats.

BACKGROUND/AIMS: Published data regarding the effects of common cardiovascular diseases, i.e. aortic stenosis on renal regulation of major vasoconstrictive (renin, endothelins) and vasodilatory systems (NO) are controversial. Therefore we aimed to evaluate the effects of chronic aortic stenosis on the renal renin-angiotensin, endothelin and NO systems. METHODS: Experimental supravalvular aortic stenosis was induced by using silver clips with a 0.6 mm internal diameter on the ascending aorta of weanling rats. Renal endothelin-1 (ET-1), endothelin-3 (ET-3), renin, AT(1a), AT(1b), eNOS, and bNOS gene expression were assessed by RNase protection assay. RESULTS: Renal renin gene expression increased twofold in rats with aortic stenosis. In contrast, renal ET-1, ET-3, eNOS, bNOS, and AT(1a), AT(1b) gene expression were unchanged in rats with aortic stenosis. CONCLUSION: Our study demonstrates that in rats with severe experimental supravalvular aortic stenosis only renal renin gene expression is stimulated. This contrasts with severe heart failure where endothelins and NO synthases are also upregulated. Different patterns of regulation of renal vasoactive mediators may be of importance for the extent of the renal impairment associated with aortic stenosis, and may be correlated with the severity of congestive heart failure.

Animals↗

PubMedDate not supplied

Regulation of glucose transporters in human peritoneal mesothelial cells.

BACKGROUND: Risk factors for peritoneal fibrosis and mesothelial cell (MsC) injury in CAPD are infections and bioincompatibility of the dialysate, including high glucose concentrations. To study a potential link between dialysate and glucose toxicity in MsC, we investigated the expression of facilitative glucose transporters (GLUT), which could contribute to glucose toxicity. METHODS: After induction of cell differentiation, MsC were incubated in regular medium or medium with 60 mM D-glucose, 30 mM glucose plus 30 mM mannitol, 60 mM mannitol, PD effluent, or with a cytokine mix. Expression of GLUT1, GLUT3, SGLT and GAPDH/L32 was studied by RNase protection assay. MsC were incubated under identical conditions with 14C-fluoro-deoxy-glucose for 30 minutes and glucose uptake was measured. To estimate Vmax and Km, 14C-fluoro-deoxy-glucose uptake rates were determined over a range of 0.6 to 10 mM unlabeled glucose. RESULTS: The cytokine mix significantly stimulated GLUT1 expression (3-fold) and GLUT3 (1.7-fold). There was a 1.4-fold increase in GLUT1 (p<0.05) and a 1.7-fold increase in GLUT3 (p<0.05) after incubation in high glucose but not in mannitol or PD-effluent controls. Glucose uptake studies confirmed this increase after incubation in 30 mM (p<0.05) and 60 mM glucose solutions. Kinetic studies showed the Km was approximately 3.7 mM for this transport. CONCLUSIONS: GLUT mRNA expression and glucose uptake are induced by high ambient glucose concentrations and cytokines. Unlike many other cells, MsC are not able to protect themselves from increased glucose concentrations by downregulation of GLUTs. The intracellular glucose concentration may therefore increase during CAPD, affecting growth factor expression and glycosylation, and contributing to glucose toxicity.

Biological Transport, Active↗

PubMedDate not supplied

New immunosuppressive strategies in renal transplant recipients.

Along with expanded knowledge of pathophysiological processes involved in transplant rejection, a variety of immunosuppressive agents with very specific modes of action have been developed. The focus of this review is an update on the pathophysiologic rationale and experience with such agents in human renal transplantation that are currently clinically available or are under investigation in human trials. Clinical data are reviewed with respect to calcineurin inhibitor sparing regimens based on mycophenolate or sirolimus, the use of leflunomide and its derivative FK778, modulation of chemotaxis with FTY720 or chemokine receptor blockers and the results of costimulatory blockade. While selection of one of these strategies may allow a more individualised therapy, the immunosuppressive potential of each compound has to be weighed against adverse reactions for an individual patient.

Alkynes↗