Biomedical subjects

C Wanner

Publications and source records attributed to C Wanner.

152 records · Page 9Linked to original sources

PubMedDate not supplied

Modification of lipoproteins in uremia: oxidation, glycation and carbamoylation.

Lipoprotein modification occurs in uremic patients and in patients with end stage kidney disease under chronic renal replacement therapy. Forms of lipoprotein modification include lipid peroxidation, glycation, and carbamoylation. In this short review, we discuss the presence of these forms of lipoprotein modification and their association with various renal diseases. Methods to analyze lipoprotein modification are introduced, and functional consequences related to vascular and renal function are presented.

Arteriosclerosis↗

PubMedDate not supplied

Effect of bradykinin on the cytosolic free calcium activity and phosphoinositol turnover in human glomerular epithelial cells.

The effect of bradykinin (BK) on the intracellular free calcium activity [Ca2+]i and phosphoinositide (PI) turnover was investigated in human glomerular epithelial cells (GEC) in culture. Human GEC exhibited a baseline [Ca2+]i of 114 +/- 3 nmol (n = 81). BK (ED50 10(-9) mol/l) caused a rapid and transient increase in [Ca2+]i, which could also be observed in the absence of extracellular calcium. The effect of BK (10(-8) mol/l) on the [Ca2+]i was inhibited by the BK2 antagonist Hoe 140 (IC50 10(-8) mol/l). BK also induced PI turnover in a time- and dose-dependent manner. A transient increase in (1,4,5)-inositol-triphosphate (InsP3) formation from 1,445 +/- 119 to 4,629 +/- 323 cpm occurred after 5 s. Stimulation of protein kinase C (PKC) by short-term preincubation (15 min) of human GEC with phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent inhibition of the BK-stimulated (10(-7) mol/l) inositol-phosphate formation. Downregulation of PKC by preincubation of human GEC with PMA (24 h, 10(-6) mol/l) or inhibition of PKC by pretreatment with staurosporin (1 h, 10(-6) mol/l) resulted in a slight but significant augmentation of the BK-induced InsP3 stimulation. The data indicate that BK induces stimulation of [Ca2+]i and PI turnover via a BK2 receptor in human GEC. PKC might exert a negative feedback function for the BK-induced PI turnover.

Bradykinin↗

PubMedDate not supplied

Proteinases in catabolism and malnutrition.

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMedDate not supplied

Lipid changes and statins in chronic renal insufficiency and dialysis.

Chronic renal failure patients suffer from a secondary form of complex dyslipidemia, similar to the so-called atherogenic dyslipidemia in insulin resistant patients or to diabetic dyslipidemia. The most important abnormalities are an increase in the serum level of triglyceride (elevated VLDL-remnants/IDL), small LDL particles and a low HDL cholesterol. The highly atherogenic LDL subclass, namely LDL-6 or small dense LDL, accumulates in hypertriglyceridemic diabetic hemodialysis patients. All these lipoprotein particles contain apoB, thus much of this complex disorder can be summarized as an elevation of triglyceride-rich apoB containing complex lipoprotein particles. Growing evidence suggests that all of the components of this type of dyslipidemia are independently atherogenic. Further disturbances exist in the dynamics of cholesterol exchange between the various lipoprotein particles and in transport from cells to catabolic sites. The European Joint Task Force and the US National Cholesterol Education Program expert panel have issued guidelines for the general population to lower the cardiovascular risk in hyper- and dyslipidemias. There is preliminary consensus that these guidelines should be applied to dialysis patients. However, the genesis of atherosclerosis in the dialysis population may be different and real benefit from lipid-lowering has not yet been demonstrated in this population. Large-scale, prospective randomized trials (4D-trial, HARP) are underway to determine whether statins reduce cardiovascular complications in diabetic and non-diabetic patients with end-stage renal disease (ESRD) and on hemodialysis treatment.

Humans↗

PubMedDate not supplied

Endotoxin-induced acute renal failure in rats: effects of L-arginine and nitric oxide synthase inhibition on renal function.

BACKGROUND: The regulation of renal hemodynamics is closely related to the L-arginine (L-Arg)/nitric oxide (NO) pathway. NO - metabolized from L-Arg - is capable of improving renal function in ischemic and toxic acute renal failure (ARF), while NO synthase (NOS) inhibition induces deterioration in renal function. The mortality rate in patients with septic shock is increased when treated with a non-selective NOS inhibitor, while the incidence of ARF requiring renal replacement therapy is unaffected. To date, there are no studies on the impact of NOS substrate (L-Arg) and inhibitor (L-NMMA) on renal function in early lipopolysaccharide (LPS)-induced ARF. METHODS: ARF was induced by intravenous (i.v.) LPS. Animals were treated with L-Arg, L-NMMA (NOS substrate and inhibitor), a combination of both or saline. Glomerular filtration rate (GFR), urine flow, fractional sodium excretion, excretion of NO metabolism stable end products and blood pressure (BP) were recorded at baseline, after ARF induction, during drug infusion and thereafter. RESULTS: L-Arg induced better GFR during infusion. Excretion of the NO metabolism end products was highest in the L-Arg group and lowest in the NOS inhibitor group. L-Arg administration had no influence on BP, while L-NMMA induced a slight elevation. CONCLUSIONS: We conclude that exogenous L-Arg exerts beneficial effects in early LPS-induced ARF in rats during drug infusion, while NOS inhibition has no influence on GFR. Subcellular compartmentalization of the L-Arg pool in cytoplasma and the rapid utilization of exogenous L-Arg in such a micro-environment could explain this effect, which has been observed in other ARF models and was called the "L-Arg paradox". In further studies the effects of early and prolonged administration of L-Arg in endotoxinemia should be investigated.

Acute Kidney Injury↗

PubMedDate not supplied

Prognostic value of tumour microvessel density in cancer of the uterine cervix stage IB to IIB.

High intensity of tumour angiogenesis has been correlated with an increased potential of metastasis and poor prognosis in human malignancies. We investigated 43 patients with cervical cancer stages IB (n = 13), IIA (n = 8) and IIB (n = 22). All patients were treated by radical hysterectomy and lymphadenectomy. In the tumour specimen blood vessels were highlighted by staining endothelial cells for factor VIII. Microvessels were counted on a 200x field (0.74 mm2) in the most active areas of neovascularisation. The mean microvessel counts per field for stage IB, IIA and IIB tumours were 59.6 +/- 28.1, 56.3 +/- 24.3 and 55.7 +/- 55.6, respectively (p-value = n.s.). We found no significant correlation of microvessel density and established prognostic factors like pelvic lymph node involvement, vascular space invasion and stromal reaction. Patients with tumours showing low microvessel density (< 40 microvessels per field) had a significantly poorer recurrence-free interval (log-rank test: p-value = 0.01).

Female↗

PubMedDate not supplied

Elevated lipoprotein(a) and fibrinogen levels [corrected] increase the cardiovascular risk in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To analyze the relationship between lipoprotein(a) [Lp(a)] and fibrinogen as potential cardiovascular risk factors in patients on continuous ambulatory peritoneal dialysis (CAPD). PATIENTS: A total of 47 uremic patients receiving CAPD, 21 with coronary artery disease (CAD), 26 without CAD. MEASUREMENTS: Lp(a) levels were determined by an immunoradiometric assay. Since Lp(a) serum concentrations vary depending on the size, apoprotein(a) [apo(a)] isoforms were determined (Westernblot). Fibrinogen was quantified according to Clauss. RESULTS: The mean Lp(a) serum concentration was 43 +/- 5 mg/dL (SEM) (median 33 mg/dL) in CAPD patients and 21 +/- 2 mg/dL (8 mg/dL) in controls (p < 0.01). Patients with low molecular weight apo(a) isoforms exhibited substantially elevated Lp(a) levels when compared with patients with high molecular isoforms (p < 0.01). In addition, we found elevated fibrinogen levels in the CAPD patients (538 +/- 61 mg/dL) compared with healthy controls (288 +/- 46 mg/dL). Twenty-one CAPD patients (45%) were suffering from CAD. Patients with CAD had higher Lp(a) levels (54 +/- 5 mg/dL vs 34 +/- 4 mg/dL) as well as higher fibrinogen concentrations (628 +/- 59 mg/dL vs 459 +/- 46 mg/dL). Furthermore, a positive correlation between the fibrinogen levels and the Lp(a) serum concentration was observed (r = 0.45, p = 0.01). CONCLUSION: We suggest that elevated Lp(a) levels are influenced by the allelic variation of the apo(a) isoform. In addition to the typical dyslipidemia found in CAPD patients, high levels of Lp(a) and fibrinogen may contribute to the elevated risk of coronary artery disease and other cardiovascular complications.

Adult↗

PubMedDate not supplied

CD-44 is not involved in the metastatic spread of ovarian cancer in vivo.

It has been shown that isoforms of the adhesion molecule CD44 are involved in the metastatic spread of several human malignancies. To determine whether CD44 plays a role in metastasis of human ovarian cancer, the tumours and corresponding metastases of 28 patients were investigated. CD44 was detected by immunohistochemistry in 2 primary tumours (7.1%) and 3 metastases (10.7%). In no case did both the primary tumour and metastasis show CD44 expression simultaneously. The results presented here suggest that CD44 does not play a crucial role in the metastatic spread of human ovarian cancer.

Adult↗