Modulation of spontaneous myometrial activity in chronically instrumented ovariectomized sheep

The uterine electromyogram (EMG) and intrauterine pressure curves (IUP) were investigated as indicators of myometrial activity in chronically instrumented, ovariectomized ewes. Spontaneous electrical activity was characterized by rhythmic patterns of trains of bursts accompanied by IUP waves. Administration of adrenergic (propranolol or phentolamine) or cholinergic (atropine) blocking agents had no effect on spontaneous uterine activity. Both oxytocin and PGF2 alpha appeared to stimulate spontaneous myometrial activity. 17beta-Estradiol temporarily depressed uterine activity in a dose-dependent fashion. The period of relaxation was followed by a pronounced increase in activity. Progesterone treatment resulted in long-term suppression of myometrial activity. Oxytocin and PGF2alpha increased EMG and IUP activity during estradiol suppression but not after progesterone treatment. These results indicate that the myometrium is active in chronically instrumented, ovariectomized ewes. The autonomic nervous system or its receptors do not play a role in the maintenance of spontaneous myometrial activity, estradiol and progesterone suppress myometrical activity but by different mechanisms.     

Hemodynamic measurements in preeclampsia: preliminary observations

Ten patients with preeclampsia were monitored with a Swan-Ganz thermodilution catheter before the start of treatment. Reference data were obtained by right-heart catheterization in four normal pregnant women. In the preeclamptic group the effects of volume expansion and vasodilatation were studied. All patients showed a low cardiac index, low pulmonary capillary wedge pressure, and a high systemic vascular resistance. Following volume expansion the pulmonary capillary wedge pressure and cardiac index rose to normal pregnant values whereas blood pressure showed no significant change and systemic vascular resistance decreased, but normal pregnant values were not obtained. Vasodilatation with dihydralazine resulted in a further decrease in systemic vascular resistance, a fall in blood pressure accompanied by a further increase in cardiac index with a stable pulmonary capillary wedge pressure. It is concluded that pregnant women with preeclampsia are unable to cope with a circulating volume necessary to maintain a cardiac index and ventricular filling pressure which is considered to be physiologic in normal pregnancy. In preeclampsia the capacity for vasodilatation is inadequate.     

Dopamine precursors and brain function in phenylalanine hydroxylase deficiency

Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. In experimental studies it has been shown that the synthesis and release of dopamine can be influenced by an increase in the availability of tyrosine. In PHD an extra dietary intake of three doses of tyrosine (160mg/kg/24h) induced a shortsning of reaction time and decreased variability, and in a double-blind crossover study a similar dose has been reported to induce an improvement on psychological tests. In a study with lower doses of tyrosine (110mg/kg/24h) no effect was found on reaction time tests. These findings need to be substantiated, and more detailed information should be obtained.     

Soluble tumor necrosis factor receptor II and soluble cell adhesion molecule 1 as markers of tumor necrosis factor-alpha release in preeclampsia

BACKGROUND: The purpose of this case-controlled study was to investigate whether plasma concentrations of TNF-receptors I and II and tumor necrosis factor-alpha-induced cell adhesion molecule 1 VCAM-1 could serve as more sensitive markers of tumor necrosis factor-alpha release in preeclamptic women than a direct measurement of circulating tumor necrosis factor-alpha. METHODS: Plasma concentrations of soluble tumor necrosis factor receptor I and II, immunoreactive tumor necrosis factor-a and soluble cell adhesion molecule VCAM-1 were determined in 21 patients with severe proteinuric preeclampsia (23-35 weeks' gestation) and 21 gestational age-matched normotensive controls by enzyme-linked immunoassays. Concentrations of bioactive tumor necrosis factor-alpha were assessed by the WEHI 164 bioassay. Data were statistically evaluated by Wilcoxon's rank sum and sign tests, and Spearman's test was used to evaluate clinical and biochemical correlations. RESULTS: Bioactive tumor necrosis factor-alpha was detected in 19 of 21 preeclamptic and 18 of 21 normotensive women, with no difference in plasma concentrations between both groups. Immunoreactive tumor necrosis factor-alpha, soluble TNF-receptors and soluble cell adhesion molecule VCAM-1 were significantly increased in plasma of preeclamptic patients, and a statistically significant positive correlation was observed between immunoreactive tumor necrosis factor-alpha and TNFRII. In preeclamptic patients a statistically significant negative correlation was observed between TNFRII and platelet count, and between soluble cell adhesion molecule VCAM-1 and birthweight ratio. CONCLUSION: These results show that plasma concentrations of soluble tumor necrosis factor receptor II and soluble cell adhesion molecule VCAM-1 reflect the release of tumor necrosis factor-alpha and provide sensitive markers of excessive release of this cytokine in preeclampsia.