Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima–media thickness in nonobese sleep apnea patients

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F_2t-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F_2t-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima–media thickness (IMT). Urinary 15-F_2t-isoprostanes were measured by liquid chromatography–tandem mass spectrometry. Urinary 15-F_2t-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2 ± 7.3 vs 12.3 ± 2.8 ng/mmol creatinine; P = 0.020). Mean carotid IMT was correlated with 15-F_2t-isoprostane (r = 0.532; P < 0.001) and with the apnea–hypopnea index (r = 0.345; P = 0.029). 15-F_2t-Isoprostane level was related to the night time spent at SaO₂ < 90% (r = 0.478; P = 0.002), the apnea–hypopnea index (r = 0.465; P = 0.003), and the mean nocturnal SaO₂ (r = ? 0.424; P = 0.007). These results showed a relationship between lipid peroxidation, carotid intima–media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.     

Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling

Gene expression profiling technology is expected to advance our understanding of genotoxic mechanisms involving direct or indirect interaction with DNA. We exposed human lymphoblastoid TK6 cells to 14 anticancer drugs (vincristine, paclitaxel, etoposide, daunorubicin, camptothecin, amsacrine, cytosine arabinoside, hydroxyurea, methotrexate, 5-fluorouracil, cisplatin, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), and bleomycin) for 4-h and examined them immediately or after a 20-h recovery period. Cytotoxicity and genotoxicity, respectively, were evaluated by cell counting and by in vitro micronucleus assay at 24h. Effects on the cell cycle were determined by flow cytometry at 4 and 24h. Gene expression was profiled at both sampling times by using human Affymetrix U133A GeneChips (22K). Bioanalysis was done with Resolver/Rosetta software and an in-house annotation program. Cell cycle analysis and gene expression profiling allowed us to classify the drugs according to their mechanisms of action. The molecular signature is composed of 28 marker genes mainly involved in signal transduction and cell cycle pathways. Our results suggest that these marker genes could be used as a predictive model to classify genotoxins according to their direct or indirect interaction with DNA.     

The ethics of cesarean section on maternal request: a feminist critique of the American College of Obstetricians and Gynecologists' position on patient-choice surgery

In recent years, the medical establishment has been speaking in favor of women's autonomy in childbirth by advocating cesarean delivery on maternal request (CDMR). This paper offers to look at the ethical dimension of CDMR through a feminist critique of the medicalization of childbirth and its influence on present-day medical ethics. I claim that the medicalization of childbirth reflects a sexist bias with regard to conceptions of the body and needs to be used with caution when applied to women's reproductive health. I then use this perspective to critically analyze the position of the American College of Obstetricians and Gynecologists (ACOG) on the ethics of decision-making in patient-choice surgery. I claim that informed consent cannot be meaningfully exercised unless women are made aware of the sexist underpinnings of the medical model of childbirth and its influence on the ethical reasoning of the American College of Obstetricians and Gynecologists. I also express concern about the effects of normalizing patient-choice cesarean sections on the choices available to pregnant women using as examples the institutional rules on mandatory cesarean sections for women with a previous cesarean delivery or breech presentation. I conclude with a call for more research into the real cost of convenience in CDMR, particularly as our increasingly strained publicly funded healthcare system would greatly benefit from the de-medicalization of normal body functions rather than an increased dependence on costly surgical technology.     

Role of alpha1beta1-integrin in arterial stiffness and angiotensin-induced arterial wall hypertrophy in mice

We examined the arterial phenotype of mice lacking alpha(1)-integrin (alpha(1)(-/-)) at baseline and after 4 wk of ANG II or norepinephrine (NE) administration. Arterial mechanical properties were determined in the carotid artery (CA). Integrin expression, MAPK kinases, and focal adhesion kinase (FAK) were assessed in the aorta. No change in arterial pressure was observed in alpha(1)(-/-) mice. Elastic modulus-wall stress curves were similar in alpha(1)(-/-) and alpha(1)(+/+) animals, indicating no change in arterial stiffness. The rupture pressure was lower in alpha(1)(-/-) mice, demonstrating decreased mechanical strength. Lack of alpha(1)-integrin was accompanied by an increase in beta(1)-, alpha(v)-, and alpha(5)-integrins but no change in alpha(2)-integrin. ANG II increased medial cross-sectional area of the CA in alpha(1)(+/+), but not alpha(1)(-/-), mice, whereas equivalent pressor doses of NE did not produce a significant increase in either group. In alpha(1)(+/+) mice, ANG II induced alpha(1)-integrin expression and smooth muscle cell (SMC) hypertrophy in the CA in association with increased aortic expression of alpha-smooth muscle actin and smooth muscle myosin heavy chain and phosphorylation of ERK1/2, p38 MAPK, and FAK. ANG II did not induce SMC hypertrophy or phosphorylation of p38 MAPK and FAK in alpha(1)(-/-) mice. A functional anti-alpha(1)-integrin antibody inhibited in vitro the ANG II-induced phosphorylation of FAK and p38 MAPK. In conclusion, alpha(1)(-/-) mice exhibit a reduced mechanical strength at baseline and a lack of ANG II-induced SMC hypertrophy. These results emphasize the importance of alpha(1)beta(1)-integrin in p38 MAPK and FAK phosphorylation during vascular hypertrophy in response to ANG II.     

Blood and cloacal swab sampling for avian influenza monitoring has no effect on survival rates of free‐ranging ducks

Concerns about the spread of avian influenza viruses (AIVs) have led to cloacal swab sampling of hundreds of thousands of birds worldwide as part of AIV surveillance schemes, but the effects of cloacal swabbing have not been adequately evaluated. We tested for differences between swabbed, swabbed and bled, and non‐sampled wild ducks in terms of live re‐encounter and dead recoveries for Common Pochard Aythya ferina and Tufted Duck Aythya fuligula, and also determined re‐encounter and recovery rates for Mallard Anas platyrhynchos and Common Teal Anas crecca. No effects of sampling methods were detected, except in Teal. Re‐encounter rates were lower in sampled Teal than in controls, with annual re‐encounter probabilities being 25% and 35% lower in males and females, respectively. Teal possibly left or avoided sampling sites, or sought sites where they were less detectable after sampling. In general, no deleterious effects were found, suggesting that cloacal swabbing and blood sampling are suitable methods for conducting AIV surveillance in ducks.     

The red death meets the abdominal bristle: Polygenic mutation for susceptibility to a bacterial pathogen in Caenorhabditis elegans

Understanding the genetic basis of susceptibility to pathogens is an important goal of medicine and of evolutionary biology. A key first step toward understanding the genetics and evolution of any phenotypic trait is characterizing the role of mutation. However, the rate at which mutation introduces genetic variance for pathogen susceptibility in any organism is essentially unknown. Here, we quantify the per‐generation input of genetic variance by mutation (VM) for susceptibility of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa (defined as the median time of death, LT50). VM for LT50 is slightly less than VM for a variety of life‐history and morphological traits in this strain of C. elegans, but is well within the range of reported values in a variety of organisms. Mean LT50 did not change significantly over 250 generations of mutation accumulation. Comparison of VM to the standing genetic variance (VG) implies a strength of selection against new mutations of a few tenths of a percent. These results suggest that the substantial standing genetic variation for susceptibility of C. elegans to P. aeruginosa can be explained by polygenic mutation coupled with purifying selection.