Ductus arteriosus flow velocity modulation by fetal breathing movements as a measure of fetal lung development

A test is needed that would accurately predict favorable neonatal lung performance in the presence of prolonged severe oligohydramnios caused by ruptured membranes so that optimal obstetric care can be provided. We propose such a test that is based on the degree of modulation of fetal ductal blood flow velocity by fetal breathing movements after maternal glucose loading. In a prospective cross-sectional study of 49 normal pregnancies (50 fetuses) between 25 and 38 weeks an exponential increase in breathing-related ductal blood flow velocity modulation was observed with advancing gestational age, reflecting the developing pulmonary vascular bed. Fetal ductal flow velocity waveforms were also recorded in 13 cases of prolonged severe oligohydramnios after ruptured membranes before 28 weeks' gestation. Normal ductal blood flow velocity modulation values were associated with normal neonatal lung performance, whereas reduced ductal blood flow velocity modulation values were associated with pulmonary hypoplasia. Fetal breathing-related ductal flow velocity modulation appears to be a promising predictor of neonatal lung performance.     

Alfentanil and placebo analgesia: no sex differences detected in models of experimental pain

BACKGROUND: To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach. METHODS: Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc. RESULTS: Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min). CONCLUSIONS: In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.     

Homocysteine impairs estrogen-induced vasodilation in isolated rat arterioles

OBJECTIVE: Clinical and basic studies have provided evidence that the cardiovascular protective effects of estrogens are partly due to effects on vasoreactivity and changes in homocysteine metabolism. Moreover, homocysteine has also been shown to influence vasoreactivity. We investigated the influence of homocysteine on the rapid vasodilatory effects of estradiol in an isolated vessel setup. DESIGN: Isolated, spontaneously constricted, gracilis muscle arterioles (diameter approximately 50 micromol/L) from female Wistar rats were cumulatively exposed to 10-10 to 10-4 mol/L 17beta-estradiol in the presence of 50 micromol/L homocysteine or N-nitro-L-arginine (L-NA) (a blocker of nitric oxide synthesis), or both. Control experiments were done without L-NA or homocysteine (n = 6 for each series). RESULTS: The dose-dependent dilation during short-term exposure to 17beta-estradiol was significantly less or absent in arterioles where L-NA, homocysteine, or both were present. The addition of 50 micromol/L homocysteine significantly increased the spontaneous constriction by 6% to 10%. CONCLUSIONS: We showed that a pathophysiological concentration of homocysteine increases the spontaneous arteriolar constriction and inhibits the 17beta-estradiol-induced, endothelium-mediated, rapid vasodilatory effect on muscle arterioles from the female rat. The endothelium-independent vasodilation remained unchanged.     

Serum S100beta increases in marathon runners reflect extracranial release rather than glial damage

The contribution of extracranial tissue damage to serum S100beta increases was examined in 18 marathon runners without clinical or laboratory signs of brain damage. Postrace serum S100beta and creatine kinase (CK) concentrations increased (p < 0.001), and areas under the curve were highly correlated (p = 0.001). To conclude, serum S100beta increases after running originate from extracranial sources. CK determination may improve specificity of S100beta as a marker of brain tissue damage in acute trauma.     

Alterations in intracellular calcium signaling of lymphocytes after exhaustive exercise

PURPOSE: Exhaustive exercise is accompanied by pronounced quantitative changes in leukocytes. Whereas most studies on lymphocytes have concentrated on their proliferative responses or cytokine secretion, not much is known about exercise-induced changes in intracellular signal transduction processes. In lymphocytes, the concentration of intracellular free calcium ([Ca(2+)](i)) is an important intracellular second messenger linking extracellular stimuli to cellular responses. The aim of the present study was to examine the effect of exhaustive exercise on the calcium homeostasis of lymphocytes. METHODS: Healthy volunteers underwent treadmill exercise at 80% of their maximal oxygen uptake until exhaustion. Blood samples were taken before, immediately after, 1 h after, and 1 d after the test. Lymphocyte subsets were analyzed by flow cytometry; isolation of lymphocytes was performed by density gradient centrifugation. [Ca(2+)](i) was measured using the calcium-sensitive fluorescent dye Fura-2. RESULTS: Compared with preexercise conditions, basal [Ca(2+)](i) was increased immediately after exercise, whereas there was no change after 1 h or 1 d. The anti-CD3- and phytohemagglutinin-induced Ca(2+) responses demonstrated a bivalent pattern. Immediately after exercise, Ca(2+) transients were impaired, whereas 1 h after and 1 d after the test, the Ca(2+) responses were increased. In contrast, the Ca(2+) responses induced by thapsigargin were not different at any time interval. Lymphocyte subsets increased immediately after exercise, especially natural killer cells and CD8+ T cells, and decreased below preexercise levels after 1 h. One day after exercise, cell counts were not different from preexercise levels. CONCLUSIONS: Taken together, this novel approach demonstrates that exhaustive exercise has a profound influence on intracellular calcium signaling of lymphocytes. These effects may explain changes in lymphocyte function that have previously been reported.     

Effects of 15 months of 17 beta-estradiol and dydrogesterone on systolic cardiac function according to quantitative and Doppler echocardiography in healthy postmenopausal women

OBJECTIVE: Our goal was to investigate the short-term and intermediate effects of low-dose hormone replacement therapy on echocardiographic parameters of cardiac function in healthy postmenopausal women. STUDY DESIGN: In a prospective, controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were randomly assigned to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period of 3 months. The control group (n = 15) received no treatment. M-mode, quantitative 2-dimensional, and Doppler echocardiographic measurements were performed at baseline and within the 17 beta-estradiol phase at 3, 12, and 15 months. RESULTS: After 12 months significant differences in change between the 2 groups were found for left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular mass index, and stroke volume index. These differences were caused by changes in the control group rather than in the hormone replacement therapy group, in which no significant within-group changes were found. All other parameters measured showed no effect. CONCLUSION: Within 15 months of 17 beta-estradiol and dydrogesterone treatment no clinically relevant differences were found in the M-mode, quantitative 2-dimensional, and Doppler echocardiographic parameters measured in this study. It is suggested that 15 months of treatment probably is too short a period for detection of direct effects on the heart itself.