Hypoxia induces differential changes of dopamine metabolism in mature and immature mesencephalic and diencephalic cell cultures.

Perinatal hypoxia is known as a high risk factor for the development of long-lasting abnormalities in dopaminergic system. The early developmental alterations of dopamine (DA) metabolism induced by hypoxia could contribute to these abnormalities. To understand the hypoxia-induced changes of intra- and extracellular dopamine levels and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in immature dopaminergic neurons, we compared these changes in rat mesencephalic and diencephalic cell cultures on day in vitro (DIV) 2 (immature cells), DIV 8 and DIV 13 (mature cells). Cell cultures were exposed to an oxygen-free gas mixture in a Billups chamber for 2-4 hours. Mature cell cultures responded to hypoxia with an increase of DA levels in the cells and in the medium during the first 45 min (by an average of 57 and 114% respectively). Thereafter, DA levels decreased, and returned to the baseline within the next 30 min. The cellular DA levels continued to decrease up to 15% of the baseline during 255 min hypoxia whereas the extracellular DA content stabilized at the prehypoxic levels. Immature cell cultures (DIV 2) in contrast to mature ones, were unable to maintain normal extracellular DA levels during hypoxia and showed a decrease of the cellular and extracellular levels to 50% of the prehypoxic levels. DOPAC and HVA changes mimick, however, at a lower level, the pattern of DA changes during the exposure to hypoxia. In principle, in the diencephalic cell culture similar effects of hypoxia exposure on the investigated parameters were found (studied during 0-120 min). The present study demonstrates that mature and immature dopaminergic cells differ in the regulation of the extra- and intracellular DA levels during hypoxia. In immature cells the low synthetic capacity of tyrosine hydroxylase and the deficient capacities of the transport and storage processes result in decreased extracellular DA levels. This could be an important factor for the long-term modulation of the expression of tyrosine hydroxylase and subsequent long-term behavioral and/or neurological abnormalities induced by perinatal hypoxia.

Parenteral selenium supplementation in critically ill patients--effects on antioxidant metabolism.

Decreased plasma selenium (Se) levels are common in critically ill patients. Oxidative stress is regarded as one possible cause of the Se deficiency. We investigated in 20 critically ill patients with decreased plasma selenium concentrations the antioxidant metabolism during parenteral selenium supplementation (week 1: 2 x 500 micrograms; week 2:1 x 500 micrograms, week 3:3 x 100 micrograms sodium selenite). As marker of oxidative stress we measured the plasma malondialdehyde levels on days 0, 1, 3, 7, 14, and 21. The content of reduced and oxidized glutathione as well as the leucocyte activity marker elastase were estimated on the same days. Initial plasma Se levels were considerably decreased (0.44 +/- 0.1 mumol/l, mean +/- SEM). After one day of supplementation Se concentrations were in the reference range. Plasma malondialdehyde levels and the ratio of oxidized and reduced glutathione were initially elevated and decreased beginning on day 3 of supplementation. The mean elastase level was 113 +/- 10 micrograms/l on day 0. On day 3 elastase values decreased significantly (85 +/- 13 micrograms/l, p < 0.05; day 21, 19 +/- 7 micrograms/l, p < 0.001). Antioxidant metabolism showed significant changes beginning after 72 hours of therapy. This latency may be explained with the induction of the enzyme glutathione peroxidase. The lowered plasma Se concentrations measured in the critically ill patients and the significant effects on antioxidant metabolism during supplementation emphasized the importance of selenium administration in these patients.

Evaluation of oxygen availability with oxygen status algorithm in patients undergoing open heart surgery treated with epoetin beta.

We evaluated in a double-blind randomized study the effect of epoetin beta (recombinant human erythropoietin) therapy on oxygen status in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. All 76 patients enrolled in this study were randomized to the two treatment groups (5 x 500 U epoetin beta or placebo/kg body weight intravenously over a 14-day period before surgery) and received 300 mg Fe2+ per day orally before surgery. Before and after surgery the lactate level and the following parameters according to the oxygen status algorithm by Siggaard-Andersen were evaluated: arterial oxygen tension (PaO2), effective hemoglobin concentration (ceHb), arterial oxygen saturation (SaO2), oxygen half saturation tension (p50), red cell 2.3 diphosphoglycerate (2.3 DPG), arterial total oxygen concentration (ctO2), concentration of extractable oxygen (cx), and oxygen compensation factor (Qx). Therapy with epoetin beta led to increases in ceHb, PaO2, ctO2, and cx and to a decrease in Qx before surgery (p < 0.05 for PaO2, p < 0.0001 for the other parameters vs placebo). The cx in patients who received epoetin beta rose by approximately 20%, thus indicating a considerable improvement in O2 delivery. In patients receiving placebo the hemoximetric parameters remained outside the normal limits at all times after surgery, but in the epoetin beta group PaO2, ctO2, cx, and Qx returned almost to their baseline values by the second or fifth postoperative day, even though the frequency of transfusions was significantly higher in the placebo group. Whereas p50 and 2.3 DPG fell in the placebo group after surgery, these two parameters were significantly higher in the epoetin beta group and led to a further increase in cx (from 24% to 38%) versus the placebo group as a result of the right shift in the hemoglobin O2-binding curve. The postoperative incidence and severity of lactic acidosis were higher in the placebo group. Preoperative epoetin beta therapy is a safe way of providing increased extractable O2 (by 24% to 38%) and decreasing the risk of lactic acidosis after surgery. This therapy has a more favorable effect on the O2 binding curve than the transfusion of erythrocyte concentrate and enhances the effect of epoetin beta therapy on the postoperative oxygen status.

[Normal value curves for intrauterine fetal blood gas and acid-base parameters in the 2nd and 3rd trimester]. / Normwertkurven für intrauterine fetale Blutgas- und Säure-Basen-Parameter im 2. und 3. Trimenon.

OBJECTIVE: The aim of the study was to establish reference ranges for fetal blood gases and acid-base balance for the second half of the gestation. METHODS: 155 appropriate-for-gestational-age fetuses between 18 and 39 weeks of gestation underwent a diagnostic cordocentesis. From a specimen obtained from umbilical venous blood the acid-base balance and blood gases were evaluated using an AVL 995 blood gas analyzer. In detail, pH, oxygen partial pressure, and carbon dioxide partial pressure were measured and oxygen saturation, bicarbonate concentration and base excess calculated. Thereafter, a linear regression for gestational age was calculated and the 95% confidence interval established. RESULTS: pH, oxygen partial pressure, and oxygen saturation showed a significant decrease with advancing gestational age, whereas the carbon dioxide partial pressure increased. The ranges of bicarbonate and base excess did not differ significantly. CONCLUSION: The results give information about blood gases in the fetus under physiological conditions, and the reference ranges can be used for comparison in fetuses at high risk of hypoxia or acidemia.

Determination of the acid-base status in blood of patients on chronic haemodialysis and of bicarbonate in dialysate: comparison of three techniques and their mathematically derived values.

The study deals with the comparison of acid-base parameters in blood of patients on chronic haemodialysis and of bicarbonate dialysate determined by Gas-Check AVL 945, equilibration technique (ET), and a titrimetric method. The results show that an acceptable agreement exists between AVL and ET with respect to measurements of pH, pCO2, HCO3-, and base excess. However, the values obtained for total buffer base related to the actual haemoglobin concentration are significantly lower (P less than 0.001) when determined by AVL. A titrimetric method is proposed for routine measurement of HCO3- in bicarbonate dialysate. Values obtained using this method are 3-4 mmol/l higher than those determined by AVL and ET. However, when the values for pK1' and for the solubility coefficient used in the Henderson-Hasselbalch equation are replaced by those for saline-bicarbonate solutions, results obtained using the titrimetric determined values agree well with those obtained by AVL and ET.

[Successful treatment of progressive dialysis encephalopathy. Case report]. / Erfolgreiche Behandlung der progressiven Dialyseencephalopathie. Ein kasuistischer Beitrag.

A case of severe aluminium-induced dialysis dementia and osteopathy is described. Under DFO-therapy a complete remission could be achieved within 8 months.

Adaptive automatic correction in optical design.

An adaptive technique for optical design with computers is described Its distinctive features are compared with those of the well known damped least squares (DLS) method. The system of adaptive control ensures a particularly certain and rapid convergence, often of an order of magnitude quicker than the DLS method. The convergence is illustrated for a number of examples. The adaptive method enables the designer to learn the fundamental potentialities and limitations of a given optical system.