Evidence for inhibition by endothelium-derived relaxing factor of thromboxane A2 receptor-mediated vasoconstriction in the fetal vessels of the human perfused placenta.

Three inhibitors of the release or effects of endothelium-derived relaxing factor (EDRF), N-nitro-L-arginine, methylene blue and oxyhemoglobin, caused further increases in perfusion pressure during vascular constriction with submaximal concentrations of the thromboxane A2-mimetic, U46619 in fetal vessels of human placental lobules perfused in vitro. The results suggest the EDRF, released during constriction of fetal placental vessels in response to thromboxane A2 receptor stimulation, attenuates the vasoconstrictor response. Hence, impairment of EDRF release or function could contribute to the reduced placental blood flow observed in various disease states associated with increased thromboxane A2 production such as pre-eclampsia.     

Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study

The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.     

Stationäre Thrombembolieprophylaxe in der Unfallchirurgie

The presented thromboprophylactic concept includes weight bearing and ankle motion as well as breathing therapy and drug prophylaxis (antiphlogistics, analgesic drugs, heparin). Routinely performed ultrasound screening of the deep veins (legs and pelvis) before release showed a low DVT incidence of 2.5% in a prospective clinical observation of 841 inpatients. Obesity, venous insufficiency, and a history of previous thromboembolic events were associated with a significantly increased risk of thrombosis (relative risk 4.1, 4,9, and 5.8, respectively) The duration of immobilization also had a relevant influence indicating that early postoperative physiotherapy in traumatology and orthopedic surgery has a widely underestimated thromboprophylactic effect.     

Amelioration of B16F10 melanoma cells induced oxidative stress in DBA/2 mice by pentoxifylline

The constantly produced small amounts of reactive oxygen species (ROS) are reduced by anti-oxidant enzymes and cellular scavengers. The oxidative stress developed by defect in ROS clearance can result in cell injury and may lead to carcinogenesis. Pentoxifylline is a methylxanthine derivative with rheologic and membrane modifier property. We have examined whether Pentoxifylline (PTX) ameliorates oxidative stress produced in subcutaneously injected mice with B16F10 melanoma cells. Treatment of mice with PTX significantly reduced oxidative stress and attenuated the altered changes of reduced glutathione and lipid peroxides. Our findings provide an experimental basis for using PTX to attenuate oxidative stress induced by B16F10 melanoma cells in liver and lung of DBA/2 mice.     

Utility of oxygen saturation and heart rate spectral analysis obtained from pulse oximetric recordings in the diagnosis of sleep apnea syndrome

OBJECTIVES: We prospectively evaluate the spectral characteristics of nocturnal arterial oxygen saturation (SaO(2)) and heart rate variability obtained from pulse oximetric recording as a diagnostic test for obstructive sleep apnea (OSA). SUBJECTS AND MEASUREMENTS: Three hundred referred outpatients with symptoms compatible with the diagnosis of OSA were studied using nocturnal pulse oximetric recording performed simultaneously with polysomnography. Power spectral analysis of SaO(2) and heart rate data were analyzed using fast Fourier transformation of a Hamming-windowed signal. DESIGN AND RESULTS: Recording test results were classified as abnormal (suspicion of OSA) if the periodogram showed a peak in the period 30 to 70 s in either of the signals. A normal test result was defined as the absence of this peak in the periodogram in both signals. Two independent observers performed a single-blind evaluation. The total area of the periodogram (STOT), the ratio of the area enclosed in the periodogram within the period 30 to 70 s (S(30-70)), the ratio of the area enclosed in the periodogram within the period 30 to 70 s with respect to the total area of the periodogram (S), and the peak amplitude of the periodogram in the period 30 to 70 s (PA) were measured in both signals. The presence of a peak in the periodogram in either of the signals has a sensitivity of 94%, a specificity of 82%, a positive predictive value of 87%, and a negative predictive value of 92% with respect to the OSA diagnosis. The patients in the OSA group had higher values for STOT, S(30-70), S, and PA than the group without OSA. CONCLUSIONS: SaO(2) and heart rate spectral analysis obtained by nocturnal pulse oximetry as well as the identification of a peak within 30 to 70 s in either signal could be useful as a diagnostic technique for patient with OSA.     

Magnesium regulates hypoxia-stimulated apoptosis in the human placenta

Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased levels of placental apoptosis. Altered regulation of apoptosis may play an important pathophysiological role in FGR. As reduced placental perfusion and reduced oxygenation are features of FGR, one aim of this study was to determine the effects of hypoxia on apoptotic activity, as assessed by DNA laddering, of placental tissue in vitro. In addition, levels of placental apoptosis may be affected by pharmacological agents routinely used in obstetric patient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA laddering during in vitro incubation of human placentae under hypoxic conditions. Incubation of normal placental explant tissue at 37 degrees C for 1-2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not significantly higher than those in non-incubated tissue. The DNA laddering activity of placental explants after 2 h of incubation under hypoxic conditions was significantly increased with increased concentrations of magnesium, but remained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexamethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human placental tissues, and that hypoxia-stimulated placental apoptosis may be further increased by increasing the extracellular magnesium concentration.