Novel mammalian cell lines expressing reporter genes for the detection of environmental chemicals activating endogenous aryl hydrocarbon receptors (ArhR) or estrogen receptors (ER)

We have constructed two vector systems (pDMS5, pSAB2) containing the promoter regions of the human CYP1A1 gene including xenobiotic response elements or the promoter region of the Xenopus laevis vitellogenin A2 gene including estrogen response elements, respectively, and the genes for green fluorescent protein and firefly luciferase. These vectors were transfected into CHO-K1 cells. Transiently transfected cells consistently responded to 1 nmol/l TCDD (dioxin) or 10 nmol/l 17ss-estradiol, respectively, with a 3-5 fold increase in luciferase activity. Permanent cell lines were selected by culturing transiently transfected cells under continued presence of antibiotics and dilution cloning. Cells which had stably integrated the vector-DNA into the genomic DNA were selected. SiF6 cells responded to treatment with TCDD, PCB126, benzo(a)pyrene or indirubin-3'-monoxime in the concentration range between 0 and 1 micromol/l. SiG12 cells responded to treatment with bisphenol A, 4-MBC and DDT in the concentration range between 0 and 10 micromol/l. Compared with the controls, luciferase mRNA-abundance (semi-quantitative RT-PCR) and luciferase activity (luminescence assay) were elevated up to 3-fold. Resveratrol or tamoxifen, respectively, worked as full antagonists. Luciferase expression was increased upon treatment of cells with extracts of spiked soil samples indicating that our systems are suited for screening of environmental samples.     

Ökonomische Aspekte des Bronchialkarzinoms

The costs of systemic treatment of lung cancer are rising rapidly due to the use of new and targeted substances. Increases in survival will further add to this development. This explains the exemplary health economic relevance of the treatment of lung cancer, which can be analyzed using various economic methods and instruments. From epidemiologic and economic perspectives, prevention should be given highest priority but the formation of health political and social opinion is not yet completed. Valid evidence on the roles of screening interventions can be expected in the next years. In this article legal, institutional and cooperative approaches within the health care system to address this problem are discussed.     

Novel sites for phenylalkylamines: characterisation of a sodium-sensitive drug receptor with (-)-[3H]emopamil.

(-)-Emopamil ((S)-emopamil, (2S)-2-isopropyl-5-(methylphenethylamino)- 2-phenylvaleronitrile hydrochloride) is a Ca(2+)-antagonistic phenylalkylamine which also blocks serotonin (5-HT2) receptors and has antiischemic properties. The (-)-[3H]emopamil tissue distribution profile of specific binding is in striking contrast to that observed for (+)-[3H]PN 200-110 or (-)-[3H]desmethoxyverapamil: (-)-[3H]emopamil labels membrane fractions from guinea-pig liver much greater than adrenal gland greater than kidney approximately lung approximately ductus deferens approximately brain approximately skeletal muscle. Binding to liver membrane was saturable (KD = 12.8 nM, Bmax = 35 pmol/mg of protein), stereoselective, reversible (K-1 = 0.22 min-1 at 25 degrees C) and inhibited by tetraethylammonium (IC50: 1.8 mM) greater than Li+ (IC50: 12.5 mM) approximately Na+ (IC50: 13.6 mM) and [NH4+] (IC50: 79.3 mM) but not by Rb+, Cs+ or K+. The high-affinity liver membrane binding sites have a pharmacological profile that is distinct from the phenylalkylamine receptor domain of the voltage-dependent L-type Ca2+ channel. Similar sites exist in brain and other tissues, albeit with a lower density. Amiodarone, butoprozine and amiloride derivatives bind with high affinity whereas 1,4-dihydropyridines do not interact at all. It is suggested that the novel phenylalkylamine site is linked to a sodium-dependent carrier or transport system.     

Evaluation of two oxygen analyzers by computerized data acquisition and processing

Monitoring of inspired oxygen concentration during anesthesia with nitrous oxide is becoming accepted as essential. This type of monitoring demands accurate monitors that respond rapidly. We evaluated two such devices for their response patterns to rapid changes in oxygen concentration, a galvanic or “fuel cell” unit and a polarographic device. Data were stored after analog-to-digital conversion. The response patterns to stepwise changes in nitrous oxide and oxygen mixtures were recorded at flow rates ranging from 2 to 10 L/min. Both units responded accurately to all changes in the absolute oxygen concentration; the polarographic unit was, on average, twice as fast. Responsiveness to nitrous oxide was low (<0.4% at 100% nitrous oxide), and the stability of the signals was good. The 90% response time (T₉₀) was consistent for any stepwise increase or decrease in oxygen concentration between 0, 21, 33, 50, and 100%. After a step change from 0 to 100% oxygen at a gas flow rate of 10 L/min, the T₉₀ was 5.8 seconds in the polarographic device and 11.4 seconds in the galvanic device (p<0.01). After a decrease from 100 to 0% oxygen, the T₉₀ was 0.6 second longer in both monitors. Comparing flow rates of 2 L/min with 10 L/min, the T₉₀ was delayed by 1.1 and 2.3 seconds for an increase, and by 1.4 and 2.9 seconds for a decrease in oxygen concentration. Experimental data suggest that both sensors respond adequately during routine clinical use. The faster response of the polarographic device is probably of limited clinical relevance, but it may aid in calibration.     

Preoperative Evaluation of Patients with Possible Coronary Artery Disease

During noncardiac surgery, patients may be at risk for developing cardiac events, related to underlying coronary artery disease. Therefore, perioperative cardiac complications remain an area of clinical interest and concern in patients undergoing noncardiac surgery. Over the years, perioperative risk assessment has evolved significantly to detect surgical patients with myocardium at risk due the coronary artery disease. In addition, many efforts have been made to reduce the cardiac risk of patients undergoing noncardiac surgery. The present review article will focus on the definition of high cardiac risk surgery and will discuss patient-related cardiac risk factors. In addition, the preoperative cardiac tests available to detect patients with coronary artery disease and strategies to reduce perioperative cardiac risk, as recommended in most recent perioperative guidelines, will be outlined.     

Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease

Objective

Metabolic syndrome (MetSyn) is a well-known risk factor for cardiovascular (CV) disease in the general population; however, the additional predictive value for CV events in high-risk patients with peripheral arterial disease (PAD) is unknown. The aims of the current study were to assess and compare: (1) prevalence of MetSyn, and (2) predictive value of MetSyn for CV events, in patients with either occlusive or aneurysmatic PAD.

Methods

We screened 2069 patients scheduled for lower occlusive arterial revascularization (n = 1031) or abdominal aortic aneurysm repair (n = 1038) for the presence of MetSyn. Adult Treatment Panel III report (ATP III) was used for defining MetSyn. Central obesity was defined as body-mass-index >30 kg/m². Main outcomes were the occurrence of CV events and CV mortality during a median follow-up of 6 years (IQR 2–9 years).

Results

Metabolic syndrome was diagnosed in 421 (41%) and 432 (42%) patients with occlusive and aneurysmatic PAD, respectively (p = 0.72). Patients with occlusive or aneurysmatic PAD and MetSyn had an increased risk for the development of CV events, when compared to patients without MetSyn (27% vs. 18% and 27% vs. 19%, p < 0.001, respectively). In occlusive and aneurysmatic PAD, MetSyn was independently associated with an increased risk of CV events (HR = 1.6; 95%CI 1.2–2.1 and HR = 1.4; 95%CI 1.1–1.8). No significant association between the presence of MetSyn and CV mortality was observed.

Conclusions

Metabolic syndrome is highly prevalent in high-risk PAD patients. In occlusive and aneurysmatic PAD patients, MetSyn is an independent predictor of long-term CV events.