Cerebrospinal fluid biomarkers of ß-amyloid metabolism and neuronal damage in epileptic seizures.

BACKGROUND AND PURPOSE: The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of ß-amyloid (Aß), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of Aß peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury. METHODS: Forty-five patients were included, 21 of whom had single generalized tonic-clonic seizures sGTCS), 11 had repetitive GTCS, 7 had repetitive partial seizures (rPS), 6 had single partial seizure (sPS) and 4 fulfilled the criterion for non-convulsive status epilepticus (nSE). CSF was analyzed for Aßx-38, Aßx-40, Aßx-42, Aß1-42, soluble APP fragments (sAPP-α/ß), total-tau (T-tau) and phosphorylated tau (P-tau), as well as heart-type fatty acid binding protein (H-FABP). RESULTS: Patients with seizures had decreased levels of T-tau (P = 0.0016) and P-tau (P = 0.0028) compared with controls, but no differences in H-FABP (P = 0.67). There were no overall differences in Aß or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Aßx-38 and Aßx-40 were elevated compared with nSE (P < 0.01), sPS (P < 0.05) and controls (P < 0.05), and Aßx-42 was elevated in rPS relative to nSE (P < 0.05). CONCLUSIONS: The findings of this study argue against acute neuronal injury following medically treated seizures but suggest that seizures may reduce CSF levels of tau. Although seizures generally did not affect CSF levels of Aß or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism.

Effect of recombinant human erythropoietin on adrenergic activity in normotensive hemodialysis patients.

Ten normotensive hemodialysis patients with severe anemia participated in the study. Human recombinant erythropoietin (rHuEpo) was administered i.v. 3 times a week in doses of 50 U/kg of body weight. During 12 weeks of observation, the mean hematocrit value increased from 19%, before start of therapy, to 32%. Simultaneous monitoring of serum plasma noradrenaline (NA) concentration showed an elevation from 202 to 281 pg/ml. An increase of NA concentration after a cold pressure stimulating test (CP) was not statistically significant after as compared to before treatment, but became statistically significant after 12 weeks of rHuEpo therapy (281 pg/ml before to 441 pg/ml after CP test, p < 0.01). The mean arterial blood pressure increased from 92 - 109 mmHg after 12 weeks of rHuEpo therapy (p < 0.001). We have demonstrated significantly increased NA blood concentrations after 12 weeks of rHuEPO therapy in normotensive patients, which correlated with increased MAP. This may suggest that the observed increase of noradrenaline concentration as a vasoactive substance after the CP test may contribute to hypertension during rHuEPO therapy.

Subcutaneous r-HuEPO therapy in CAPD patients: dose determination and clinical experience.

We present our results on the efficacy and safety of low dose r-HuEPO given subcutaneously in the treatment of anaemia in CAPD. We have studied 10 stable patients (5 males, 5 females) on CAPD. In our study subcutaneous r-HuEPO was administered twice a week for 6 months. Mean initial dose of r-HuEPO was 67.3+/-21.7 U/kg/week, and maintenance dose was 35.8+/-12.1 U/kg/week. The target Hb concentration was 10-12 g/dl. All patients responded to r-HuEPO. During treatment significant increases of haemoglobin concentration (p<0.05), haematocrit (p<0.05), red cell count (p<0.05) and reticulocyte count (p<0.05) were observed. We found no significant changes in total white cell or platelet counts. Long-term r-HuEPO treatment did not influence significantly plasma levels of electrolytes (Na, K, Ca), urea and creatinine. We found no significant changes in ultrafiltration volumes. In the present study the mean systolic and diastolic blood pressures did not change. Liver function tests were normal at the beginning and at the end of the study. r-HuEPO treatment was associated with a decrease of ferritin (455+/-90 vs. 224+/-83 microg/l. Oral or intravenous iron substitution became necessary in 6 patients. Side effects in our study were minimal; one patient had myalgia after the first seven doses but this disappeared as treatment was continued. Two patients reported pain (mild) at the injection site. In the present study, the correction of anaemia was accompanied by a substantial improvement in the quality of life, mainly in capacity for work, household and social activities.

The effect of recombinant human erythropoietin (r-Hu EPO) administration on the blood chemistries and composition in uremic rats.

Recombinant human erythropoietin (r-Hu EPO) therapy improves the anaemia of patients on chronic hemodialysis, on peritoneal dialysis and those with chronic renal failure who have not yet started any form of renal replacement therapy. In the last category there is concern that r-Hu EPO therapy may be associated with deterioration of the reserve renal function. But new data showed that even during more prolonged treatment the correction of anaemia does not have a major detrimental effect on renal function. The study was undertaken to examine the influence of r-Hu EPO therapy on renal function and rheological erythrocytes finding in uremic rats.

Alterations in polymeric immunoglobulin receptor expression and secretory component levels in bladder carcinoma.

To assess the capacity of transitional cells to synthesize the release polymeric immunoglobulin receptor (pIg-R) in bladder carcinoma, we studied the localization of pIg-R in normal and tumor tissues and measured the levels of secretory component (SC) either in the free form or bound to Ig (S-IgA, S-IgM) in the serum and urine of 56 patients with transitional-cell carcinoma (TCC) of the bladder. In the normal bladder mucosa, pIg-R was localized in the cytoplasm and plasma membranes of the superficial cells and on all epithelial cell membranes. In TCC cases, 65% of those studied expressed pIg-R. A marked heterogeneity in pIg-R staining was observed in some tumors. Although a better expression of pIg-R in tumors with a well-preserved epithelial architecture was observed, no correlation was found between pIg-R expression and the grade or stage of the tumors in the patients under study. Three groups were established: (1) in TCC with no complications, serum levels of free SC and S-IgA were significantly increased; (2) in TCC with urinary infections (UI), serum levels of free SC and S-IgA were significantly higher than control values but lay within the same range observed in TCC with no complications and rates of urinary excretion of SC were significantly higher than those in normal subjects; (3) in TCC without UI but with hepatic disorders [high gamma-glutamyl transferase (GGT) activity], there was a correlation between serum S-IgA levels and GGT activity (r = 0.5, P less than 0.005) and serum SC levels were significantly higher than those observed in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)