Search PubMed⌕ Search

Biomedical subjects

Gert Mayer

Publications and source records attributed to Gert Mayer.

46 records · Page 3Linked to original sources
PubMed2002

Renal hemodynamic effects of somatostatin are not related to inhibition of endogenous insulin release.

BACKGROUND: Somatostatin inhibits endocrine and exocrine secretions and exerts renal vasoconstriction. The mechanism underlying somatostatin's vascular effects is unknown. Since insulin can cause vasodilation, we hypothesized that removal of basal insulin release by somatostatin may contribute to somatostatin-induced renal vasoconstriction. METHODS: The study was conducted in different protocols comprising forty-six healthy male volunteers. Randomized studies were performed to compare the effects of somatostatin alone (0.1 microg/kg/min) to the effects of somatostatin + low dose insulin (0.1 mU/kg/min), the effects of somatostatin + low dose insulin to the effects of somatostatin + high dose insulin (1.5 mU/kg/min), and the effects of insulin (1.5 mU/kg/min) + somatostatin. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured with the para-aminohippurate (PAH) and the inulin clearance technique, respectively. Blood pressure and pulse rate were measured non-invasively. RESULTS: Somatostatin alone decreased GFR (-14 +/- 6%, P < 0.001) and RPF (-16 +/- 7%, P < 0.001) whereas systemic hemodynamics were unchanged. Preceding or concomitant infusion of insulin at high doses (insulin plasma concentration of 127 +/- 25 or 144 +/- 17 microU/mL) but not co-infusion with low dose insulin (insulin plasma concentration of 11 +/- 3 microU/mL) mitigated or reversed the vasoconstrictive actions of somatostatin on GFR and RPF. CONCLUSIONS: Somatostatin induces marked renal vasoconstriction and exogenous restoration of fasting insulin concentrations does not influence the renal vascular effects. Therefore, it is unlikely that somatostatin-induced vasoconstriction is due to removal of basal insulin. Plasma insulin concentrations in the high postprandial range can reverse somatostatin-induced renal vasoconstriction, suggesting functional antagonism.

Adult↗
PubMed2002

ACE genotype and ACE inhibitor response in kidney disease: a perspective.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce blood pressure and slow the progression of renal diseases. However, a substantial interindividual variability in treatment response also has been noted. The activity of ACE is partially dependent on the presence or absence of a 287-bp element in intron 16, and this insertion/deletion (I/D) polymorphism accounts for 47% of the total phenotypic variance in plasma ACE; DD subjects have the highest; ID subjects, intermediate; and II individuals, the lowest concentrations. Data suggest that genotype also determines tissue enzyme activity, and, at least under certain conditions, ACE activity is a rate-limiting step for angiotensin II formation. It therefore has been speculated that the ACE polymorphism also might affect therapeutic effects of ACE inhibitors. Unfortunately, clinical studies performed to date do not allow us to draw definite conclusions. Nonetheless, the rapidly evolving area of pharmacogenomics soon will also affect therapeutic decisions in the field of nephrology and hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors effectively reduce proteinuria; however, the optimal antiproteinuric dose is still unknown. We conducted this study to determine whether an increase in ACE-inhibitor dose above the maximal antihypertensive effect has additional antiproteinuric potential. METHODS: Twenty-three proteinuric patients were administered the ACE inhibitor spirapril at a starting dose of 3 to 6 mg/d. The dose was increased every 6 weeks until the maximal antihypertensive effect, assessed by 24-hour ambulatory blood pressure (ABP) monitoring, was achieved (spir(max)), then increased to a supramaximal dose (spir(supramax)). Renal parameters, urinary protein excretion, and systemic activity of the renin-angiotensin system were compared between baseline, spir(max), and spir(supramax). Glomerular filtration rate and renal plasma flow were determined before the administration of spirapril and after administration of the supramaximal dose. RESULTS: Median ABP and proteinuria decreased significantly between baseline and spir(max) (median, 102 mm Hg; range, 82 to 122 mm Hg versus 97 mm Hg; range, 82 to 113 mm Hg; median protein, 2.56 g/d; range, 1.05 to 22.1 g/d versus 1.73 g/d; range, 0.42 to 4.7 g/d). Both creatinine level and creatinine clearance remained unchanged. Suppression of angiotensin II formation led to a significant increase in renin and angiotensin I concentrations and a nonsignificant decrease in aldosterone levels. The increase in spirapril to a supramaximal dose had no further effect on serum renin or angiotensin I levels or proteinuria. There was an additional slight decrease in aldosterone levels and, subsequently, a significantly lower level than at baseline. CONCLUSION: Our results show that the antiproteinuric effect of spirapril is associated with its antihypertensive effect. Although high-dose ACE-inhibitor therapy has no additional influence on proteinuria, a possible beneficial long-term effect cannot be ruled out.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Discrete simulation of regulatory homo- and heterodimerization in the apoptosis effector phase.

MOTIVATION: Quantitative simulation of molecular reaction networks is among the most promising approaches towards an understanding of complex biochemical pathways. Numerous qualitative as well as quantitative data from diverse experimental settings, in particular from genomics and proteomics, have to be contextually linked to convert static data into dynamic functionality. RESULTS: This paper presents the Lattice Molecular Automaton, a Cellular Automaton-based simulation tool, capable of representing complex molecular dynamics at different levels of granularity. A data structure concept represents molecular units, whose dynamics, embedded on a 2D grid, is defined via detailed intermolecular interaction profiles. The data structures hold diverse information as molecular type, potential, as well as kinetic energy states, which allows a precise representation of intracellular reaction networks. The molecular dynamics is performed via local computation of individual molecular states on the lattice, which, in conjunction with discretized space and time, enables excellent scalability of this simulation concept. This paper finally gives Lattice Molecular Automaton simulation results on key elements of apoptosis, the cell death cascade, in particular focusing on the regulatory function of homo- and heterodimerization of members of the Bcl-2 protein family in the apoptosis effector phase. The regulatory proteins Bcl2, Bax, and Bak constitute a diffusion-driven molecular switch with inherent damping of apoptosis induction, thereby controlling the apoptosis reaction cascade under noisy, external apoptosis inducing conditions.

Apoptosis↗
PubMed2002

Failure of BCL-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function.

SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation.

Apoptosis↗
PubMed2002

Effects of microinjection of synthetic Bcl-2 domain peptides on apoptosis of renal tubular epithelial cells.

Bcl-2 protein family members are among the key regulators of the apoptosis effector phase. Therefore, we investigated the ability of synthetic peptides derived from proteins of the Bcl-2 family, namely, the NH2-terminal region of Bcl-2 (Bcl2_syn), a central domain of Bax (Bax_syn), and a central domain of Bak (Bak_syn) to interfere with the apoptotic process in LLC-PK1 cells. Apoptosis was induced by tacrolimus or lipopolysaccharide treatment, and microinjection of Bcl2_syn into stimulated LLC-PK1 cells significantly reduced the percentage of apoptotic cells detected within 4 h after the treatment. Microinjection of Bax_syn or Bax_syn, in contrast, induced apoptosis in otherwise untreated LLC-PK1 cells during the same period of time. A random sequence control peptide (Control_syn), which served as a negative control, as well as FITC-labeled dextran, which was coinjected in all experiments for visualization, were ineffective in either preventing or inducing apoptosis. These results suggest that synthetic peptides mimicking the functional domains of proteins of the Bcl-2 family are capable of regulating apoptosis when microinjected into LLC-PK1 cells in vivo. Analogs to these regulatory peptides could therefore provide valuable lead compounds in the therapeutical context.

Animals↗
PubMedDate not supplied

Late referral defined by renal function: association with morbidity and mortality.

BACKGROUND: Many patients with chronic renal failure are referred very late to nephrology units. Late referral (LR) is reported to be associated with increased morbidity and mortality. METHODS: We used glomerular filtration rate (GFR) at the first visit to a nephrologist to define early referral (ER) and LR in a retrospective analysis. Patients admitted with a GFR < 20 mL/min/1.73 m2 were classified as LR. The 75 patients with chronic renal failure beginning renal replacement therapy (RRT) at Innsbruck University Hospital between January 1999 and October 2000 were included. Patient characteristics were compared between the two groups. Survival analysis until the end of 2002 was carried out using Cox's proportional hazard model. To identify the influence of comorbidity on mortality a comorbidity score was applied. RESULTS: Thirty-three patients were classified as ER and 42 patients as LR. Diabetic nephropathy was more frequent in the LR group (18 vs. 6 patients, p = 0.005). ER patients were significantly younger (53 +/- 16 yrs) as compared to LR patients (62 +/- 14 yrs, p = 0.012). Comorbid conditions were more frequent in the LR group (comorbidity score 1.5 +/- 1.3 for LR and 0.7 +/- 1.1 for ER, p = 0.003). During follow-up, 27 patients died, 19 from the LR group and 8 from the ER group. In the univariate analysis, comorbidity score (p < 0.001) and age (p = 0.017) were significantly associated with mortality, whereas LR patients demonstrated higher mortality (p = 0.076). By multivariate analysis the comorbidity score (p < 0.001) only was associated with mortality within at least 2 yrs of RRT. CONCLUSION: Over half of the patients with end-stage renal disease (ESRD) were referred too late, with a GFR < 20 mL/min/1.73 m2. Mortality during the 1st 2 yrs on RRT was mainly determined by comorbidity, acquired during the course of chronic renal failure. In comparison, the negative impact of LR seems to be minor and requires a larger sample size to be demonstrated.

Diabetic Nephropathies↗
PubMedDate not supplied

Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis.

BACKGROUND: Renal osteodystrophy is common in patients with chronic renal failure (CRF) on hemodialysis (HD), leading to reduced bone mineral density (BMD) and higher bone fracture incidences. Since growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are known to enhance bone metabolism and BMD, and CRF patients exhibit GH and IGF-1 resistance, recombinant human GH (rhGH) therapy could be beneficial for these patients. METHODS: This study evaluated the effects of a 12-month rhGH therapy on bone metabolism parameters; alkaline phosphatase (AP), osteocalcin (OC), procollagen I carboxyterminal propeptide (PICP), telopeptide ICTP, serum crosslaps, n-terminal propeptide of type III procollagen (PIIINP) and intact parathyroid hormone (iPTH), as well as on BMD of the lumbar spine and the femoral neck in 19 malnourished HD patients (10 females, 9 males) with a mean age of 59.3 +/- 13.4 yrs. Fourteen patients completed the 12-month study. RhGH (0.25 IU/kg) was given subcutaneously 3x/week after each dialysis session. RESULTS: IGF-1 concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/mL (p<0.01) after 3 months, followed by a slight decline over the next 9 months. PICP as a bone formation marker significantly increased after 3 months from 250.1 +/- 112.6 to 478.5 +/- 235.2 ug/L (p<0.01), as well as PIIINP, whereas OC and bone resorption parameters like ICTP showed only a slight increase (ICTP: 50.3 +/- 18.5 to 70.0 +/- 39.5 ug/L after 3 months (ns)). All bone metabolism parameters slightly declined in the following 9 months, but remained above baseline values after 12 months. PTH rose from 198.0 +/- 139.2 to 456.0 +/- 268.7 ng/ml, p<0.01 after 6 months. BMD of the lumbar spine showed a significant reduction after 3-month rhGH therapy (0.80 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, p<0.01), but returned to baseline values after 12 months. BMD of the femoral neck remained stable during the entire study. CONCLUSIONS: In summary, 12-month rhGH treatment in patients on chronic HD caused a significant increase in IGF-1, together with an increase in bone turnover. In addition, there was a temporary reduction in BMD of the lumbar spine seen, which returned to baseline values after 12 months.

Absorptiometry, Photon↗