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Biomedical subjects

W Schoeppe

Publications and source records attributed to W Schoeppe.

At least 19 recordsLinked to original sources
PubMed1992

Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury.

To evaluate whether monocytes/macrophages derived from glomeruli could be a source of increased eicosanoid and free oxygen radical formation in glomerular disease, monocytes/macrophage (M/M) were isolated from nephritic glomeruli and their in vitro generation of eicosanoids and superoxides were measured. Glomerular immune injury was induced by i.v. injection of a rabbit-anti-rat thymocyte antiserum (ATS). Kidneys were removed two, five, and 24 hours, and three and eight days after ATS. Adhesive glomerular macrophages were obtained by isolation of glomeruli, enzymatic digestion and incubation of the single cell suspensions in culture dishes. O2-production was evaluated by superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome C; PGE2 and TxB2 release was assessed by direct RIA. Glomerular macrophage infiltration was maximal 24 hours after intravenous antibody (35.9 +/- 5.1 M/M per glomerulus). In vitro production of superoxide was significantly enhanced (P less than 0.001) five hours after ATS administration (51.6 +/- 4.4 nmol O2/10(6) MM/hr), when compared with M/M from controls (30.4 +/- 2.0 nmol O2/10(6) MM/hr). TxB2 formation of glomerular M/M was increased (P less than 0.001) two hours and five hours after ATS administration (1056 +/- 75 and 1182 +/- 112 pg TxB2/10(6) MM/hr) compared with controls (390 +/- 34 pg TxB2/10(6) MM/hr). PGE2 synthesis, however, was decreased (P less than 0.01) at five hours after ATS (629 +/- 43 pg PGE2/10(6) MM/hr) compared with controls (950 +/- 125 pg PGE2/10(6) MM/hr). Furthermore, there was release of leukotriene B4 (LTB4) in monocytes of nephritic glomeruli five hours after ATS administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Thromboxane mediates glomerular haemodynamics in a model of chronic glomerular disease.

In order to evaluate a possible haemodynamic role of cyclooxygenase products in chronic renal disease, a model of chronic glomerular injury was induced in nephritic rats by unilateral nephrectomy and high dietary protein intake. Eight weeks after induction of an in situ immune complex glomerulonephritis (CGN), rats subjected to high protein (HP) intake (42% protein) and uninephrectomy revealed a significantly lower glomerular filtration rate (GFR; 485 +/- 53 microliters min-1 100 g-1 body weight (BW)) compared with uninephrectomized rats with ICGN which were on low protein (LP) diet (6% protein) (825 +/- 155 microliters min-1 100 g-1 BW) (P less than 0.01). The glomerular thromboxane B2 (TxB2) formation in uninephrectomized rats with ICGN on either LP or HP intake was not significantly different (HP: 473 +/- 61; LP: 493 +/- 63 pg mg-1 min-1), but was significantly higher when compared with non-nephritic controls on either diet. Glomerular prostaglandin E2 (PGE2) production in rats on HP diet was higher compared with rats with LP intake (HP: 617 +/- 67; LP: 351 +/- 76 pg mg-1 min-1) (P less than 0.01). The thromboxane receptor blocker daltroban significantly elevated suppressed GFR in ICGN rats on HP diet (ICGN+vehicle: 426 +/- 69; ICGN+daltro: 689 +/- 66 microliters min-1 100 g-1 BW) (P less than 0.01). Thromboxane receptor blockade had no effect on glomerular haemodynamics in ICGN animals receiving LP diet (ICGN+vehicle: 771 +/- 24; ICGN+daltro: 684 +/- 85 microliters min-1 100 g-1 BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1992

A rat model of progressive chronic glomerular sclerosis: the role of thromboxane inhibition.

In order to evaluate a possible role of thromboxane A2 (TxA2) in the pathophysiology of chronic glomerular disease, we studied the effect of a 12-wk combined treatment with the thromboxane receptor blocker Daltroban (D) and the thromboxane synthesis inhibitor UK 38485 (UK) on glomerular function and morphology in a rat model of chronic progressive glomerular injury. The glomerular lesion was induced in unilaterally nephrectomized rats by the repeated i.v. injection of an antibody directed against mesangial cells. Control rats were uninephrectomized. Three months after the first antibody injection before D and UK treatment, albuminuria (35.8 +/- 3.6 mg/24 h) and glomerular TxB2 formation (146 +/- 20 pg/mg of protein/min) were significantly higher compared with control values (albuminuria, 14.3 +/- 3.5 mg/24 h; TxB2, 59 +/- 16 pg/mg/min). Six months after antibody, albuminuria in nephritic rats had increased to 135 +/- 17 mg/24 h. In nephritic rats treated with D plus UK, albuminuria (44 +/- 12 mg/24 h), however, was significantly (P less than 0.001) inhibited. Quantitative morphological analysis (glomerular damage index) 6 months after antibody revealed significantly (P less than 0.001) increased glomerular lesions in nephritic rats (0.353 +/- 0.095) compared with that in uninephrectomized controls (0.045 +/- 0.014). The treatment of rats with D and UK significantly (P less than 0.001) reduced the glomerular damage index (0.101 +/- 0.004) in nephritic rats. D plus UK treatment reduced glomerular TxB2 formation but increased prostaglandin E2 and 6-keto prostaglandin F1 alpha release by isolated glomeruli. This study demonstrates that interventional treatment with D and UK ameliorates albuminuria and glomerular morphological lesions in a rat model of immunologically induced progressive glomerular injury.

Albuminuria↗
PubMed1992

Angiotensin II-induced proliferation of cultured murine mesangial cells: inhibitory role of atrial natriuretic peptide.

Angiotensin II (ANG II), as a single factor, induces proliferation in a cultured murine mesangial cell line (MMC). This study was undertaken to evaluate a possible influence of atrial natriuretic peptide (ANP) on this ANG II-induced proliferation. ANP (10(-7) M) for 2 min significantly increased intracellular cGMP levels in MMC. This increase in cGMP was totally abolished when cells were preincubated for 5 min with 10(-7) M ANG II. Stimulation of intracellular cGMP formation by sodium nitroprusside was also decreased in the presence of ANG II. The ANG II-mediated inhibition of ANP-stimulated intracellular cGMP levels was blocked by Dupont 753, suggesting signal transduction through ANG II receptors of the AT1 class. ANP (10(-7) M) for 24 h completely abolished the ANG II-induced proliferation in MMC. However, 10(-7) M ANP had no significant effect on mitogenesis induced by platelet-derived growth factor or epidermal growth factor. Furthermore, ANP reduced the ANG II-stimulated expression of the proliferating cell nuclear antigen, a cofactor of polymerase delta that is active in the S-phase of the cell cycle. The addition of 10(-3) M N-monobutyryl-guanosine 3':5'-cyclic monophosphate or 8-bromo-guanosine 3':5'-cyclic monophosphate also blocked the ANG II-induced proliferation. ANP (10(-7)) M for 24 h had no significant influence on the expression (number and dissociation constant) of ANG II receptors as determined by binding assays. These results suggest that, besides the previously shown vasoconstrictive and vasodilating effects, complex interactions between ANG II and ANP exist that can modulate mesangial cell growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

[Decreasing the risk of post-transfusion non-A, non-B hepatitis by anti-HCV screening].

In May 1990 a specific enzyme immunoassay (EIA) for NANBH was developed by recombinant DNA technology which detects antibodies to a virus called hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho Diagnostic Systems with recombinant antigens from Chiron Corp. based on extraction from high infectious titer chimpanzee plasma RNA after transcription into cDNA. We tested the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated anti-HCV-positive blood donors and 8.2% anti-HCV-positive hemodialysis patients.

Blood Donors↗
PubMed1992

[Management of the organ donor].

Brain death is associated with loss of hypothalamic, pituitary and brain stem function resulting in apnea, bradycardia and hypotension, poikilothermia, and diabetes insipidus. In order to preserve body functions mechanical ventilation is continued with the aim to maintain an arterial partial pressure of oxygen of more than 100 mmHg. Previous fluid restrictions and the application of diuretics during the treatment of high intracranial pressure frequently result in dehydration. Progressive vasodilation may induce severe hypotension and fluid replacement with cristalloids and if necessary colloids may be called for until the central venous pressure reaches 10 cm H2O. Continuous substitution of potassium and the use of hypotonic solutions such as glucose 5% may avoid hypokalaemia and hypernatraemia, respectively. Inotropic support with dopamine (5-10 micrograms/kg.min) or adrenaline (0.01-0.1 micrograms/kg.min) may be needed to maintain normal mean arterial blood pressure (65 mmHg). Polyuria (5000 ml/24 h) can be treated by continuous intravenous infusion of antidiuretic hormone (0.5-2-10 U/h). Hypothermia must be prevented by warming all fluids (37 degrees C) and covering the patient with heat saving blankets.

Brain Death↗
PubMed1992

Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences.

Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative.

Anemia↗
PubMed1992

Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury.

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.

Adolescent↗
PubMed1992

[Prevention of post-transfusion non-A, non-B hepatitis by anti-HCV screening].

Since May 1990 a specific enzyme immunoassay (EIA) for NANBH has been developed by recombinant DNA technology which detects antibodies to a virus called hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho-Diagnostic Systems with recombinant antigens from Chiron Corp. based on extraction from high infectious titre chimpanzee plasma RNA after transcription into cDNA. We tested the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated anti-HCV positive blood donors and 8.2% anti-HCV positive hemodialysis patients.

Antigens, Viral↗
PubMed1992

Aminopeptidase A (= angiotensinase A) in human progressive renal disease.

To elucidate factors possibly involved in adaptive cell responses due to progressive deterioration of glomerular structure and function, the activity of angiotensinase A (ATA), a glycoprotein of the glomerular tuft and of the proximal tubule, was analyzed on human kidney sections applying quantitative image analysis. Based on the software the exclusive glomerular expression of ATA was assessed in normal controls and 34 kidneys of patients with various stages of renal insufficiency (1.3-12 mg/dl serum creatinine). The data from diseased kidneys revealed a reduced total ATA-positive glomerular compartment, a larger area of remaining glomeruli, and a rise of the ATA-negative renal interstitium. Irrespective of the progression of the disease, hypertrophic glomeruli of remnant nephrons exhibited a high and homogeneous expression of ATA. Survival of glomeruli in patients with chronic renal failure correlated with the capability of glomerular cells to synthesize ATA at an increased rate, which may prevent angiotensin II-mediated growth effects, the accumulation of extracellular matrix proteins, etc., thus escaping final glomerulosclerosis.

Aminopeptidases↗
PubMed1991

[The kidney and life expectancy].

Basic renal functions are physiologically determined as precisely regulated relation between more and less physical events with low energy consumption and energy dependent cellular transport mechanisms. All well in ageing as under various conditions of renal diseases adaptive processes become biologically effective, so that stabilisation of homöostasis is possible up to a loss of 95% of normal function. Life expectancy has to be defined under the new conditions of renal replacement therapy effective beyond this biologically defined border line.

Humans↗
PubMed1991

A cell culture assay for the detection of cardiotoxicity.

An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. We propose the use of "shock protein" formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing "shock protein" formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of "shock proteins." Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes "shock protein" formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce "shock protein" synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive.

Animals↗
PubMed1991

Effects of calcium channel blockers on stress protein synthesis in cardiac myocytes.

The detection of "stress proteins," certain protein groups of 70 or 30 kDa molecular weight synthesized de novo under stress conditions, serves as an assay for monitoring cellular toxicity. Typical toxins inducing stress protein formation in cardiac myocytes are CdCl2 and H2O2. The synthesis of 68, 71, and 30 kDa stress proteins is evoked by CdCl2, and H2O2 stimulates the formation of a 30 kDa protein. When fetal mouse myocardial cells are incubated first with CdCl2 and then with H2O2 or vice versa, an additive effect on stress protein synthesis can be documented. The calcium antagonists diltiazem, verapamil, and nifedipine, at concentrations above 0.05 mg/ml, stimulate the de novo synthesis of a 30 kDa stress protein. After preincubation of the cardiac myocytes with slow calcium channel blockers, the synthesis of the 70 kDa stress protein family evoked by CdCl2 is reduced. In contrast to the increased stress protein synthesis after heart cells are exposed to toxins, preincubation with calcium antagonists reduces the formation of certain stress proteins. These results indicate an interference of calcium channel blocking drugs with stress protein formation in cultured mouse myocardial cells.

Animals↗
PubMed1991

Therapy with recombinant human erythropoietin reduces cardiac size and improves heart function in chronic hemodialysis patients.

The substitution of recombinant human erythropoietin (rhEPO) in chronic hemodialysis patients is often associated with the development of severe hypertension. In the present study, a systematical echocardiographic analysis was performed in 25 patients on maintenance hemodialysis during rhEPO therapy for at least 4 months. Referred to the total group, indices of left ventricular size decreased significantly. Left ventricular total volume and left ventricular mass were reduced considerably. Fractional fiber shortening and ejection fraction showed an impressing improvement. At a constant heart rate, stroke volume and cardiac output were reduced. Myocardial thickness did not alter under chronic rhEPO therapy. When subgroups were formed with respect to changes in blood pressure, all parameters investigated behaved very similar to the total group, irrespective of changes in blood pressure. Five patients with coronary heart disease and clinical signs of myocardial insufficiency were evaluated separately. These patients showed a decrease in left ventricular size and no evidence of a deterioration of myocardial function. We conclude from our results that rhEPO therapy in patients on maintenance renal replacement therapy has beneficial effects on left ventricular size and function; these effects are not significantly counteracted by the development of hypertension.

Anemia↗
PubMed1991

The platelet activating factor receptor antagonist WEB 2170 improves glomerular hemodynamics and morphology in a proliferative model of mesangial cell injury.

Rats were treated with the platelet activating factor receptor antagonist WEB 2170 (15 mg/kg/day) in three different protocols to evaluate a possible role of platelet activating factor in an experimental proliferative model of glomerular disease. The glomerular immune injury was initiated by the i.v. administration of a rabbit anti-rat thymocyte antiserum. Anti-rat thymocyte antiserum induces a proliferative glomerulonephritis with reduction of glomerular filtration rate (614 +/- 94) compared with controls (1,120 +/- 192 microL/min/100 g body wt) when studied at day 7. Treatment of rats with WEB 2170 over 8 days (starting at day -1; protocol 1) ameliorated the loss in glomerular filtration rate (936 +/- 82 microL/min/100 g body wt) in nephritic rats at day 7; however, it had no effect on controls (1,142 +/- 104 microL/min/100 g body wt). Interventional treatment with WEB 2170 (starting at day 4 after anti-rat thymocyte antiserum; protocol 2) also improved glomerular function when glomerular filtration rate was already reduced (410 +/- 41 microL/min/100 g body wt) at day 4. The platelet activating factor receptor antagonist given at day 7 after induction of disease (protocol 3) did not improve impaired glomerular filtration rate. Preinterventional and interventional treatment with WEB 2170 reduced the infiltration of polymorphonuclear granulocytes in glomeruli. Interventional treatment with WEB 2170 also reduced glomerular morphologic damage in nephritic glomeruli. The data demonstrate a beneficial effect of the platelet activating factor receptor antagonist in this animal model of proliferative glomerulonephritis which suggests that platelet activating factor might play an important role in the mediation of this disease.

Animals↗