Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome

<p>Abstract</p> <p>Background</p> <p>We recently showed that women with four clinical phenotypes of polycystic ovary syndrome (PCOS) do not demonstrate anatomical evidence of elevated prenatal androgen exposure as judged by a lower ratio of the index (2D) to ring (4D) finger. However, those findings conflicted with a previous study where women with PCOS had lower right hand 2D:4D compared to healthy female controls. Both these studies used Vernier calipers to measure finger lengths - a method recently shown to be less reliable at obtaining finger length measurements than computer-assisted analysis.</p> <p>Methods</p> <p>Ninety-six women diagnosed with PCOS according to the 2003 Rotterdam criteria had their finger lengths measured with computer-assisted analysis. Participants were categorized into four recognized phenotypes of PCOS and their 2D:4D compared to healthy female controls (n = 48) and men (n = 50).</p> <p>Results</p> <p>Digit ratios assessed by computer-assisted analysis in women with PCOS did not differ from female controls, but were significantly lower in men. When subjects were stratified by PCOS phenotype, 2D:4D did not differ among phenotypes or when compared to female controls.</p> <p>Conclusion</p> <p>Computer-assisted measurements validated that digit ratios of women with PCOS do not show anatomical evidence of increased prenatal androgen exposure.</p

Ruptured abdominal aortic aneurysm, a “two-hit” ischemia/reperfusion injury: Evidence from an analysis of oxidative products

AbstractPurpose: Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical–mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs. Methods: Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F2 -isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence. Results: Plasma from patients with RAAAs showed significantly elevated F2 -isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P < .0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F2 -isoprostane levels (P < .013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases. Conclusion: The F2 -isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F2 -isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs. (J Vasc Surg 1999;30:219-28.

Folic Acid Transport to the Human Fetus Is Decreased in Pregnancies with Chronic Alcohol Exposure

During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption.Serum folate was measured in maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure (n = 23) and in non-drinking controls (n = 24). In the alcohol-exposed pairs, the fetal:maternal serum folate ratio was ≤ 1.0 in over half (n = 14), whereas all but one of the controls were >1.0. Mean folate in cord samples was lower in the alcohol-exposed group than in the controls (33.15 ± 19.89 vs 45.91 ± 20.73, p = 0.04).Our results demonstrate that chronic and heavy alcohol use in pregnancy impairs folate transport to the fetus. Altered folate concentrations within the placenta and in the fetus may in part contribute to the deficits observed in the fetal alcohol spectrum disorders

Excessive formation of hydroxyl radicals and aldehyde lipid peroxidation products in cultured skin fibroblasts from patients with complex I deficiency

Previous studies suggest oxygen free radicals ’ involvement in the etiology of cardiomyopathy with cataracts. To investigate the role of free radicals in the pathogenesis of the cardiomyopathy with cataracts and complex I deficiency, fibroblasts from patients were assessed for hydroxyl radical formation and aldehydic lipid peroxidation products with and without redox active agents that increase free radicals. The rate of hydroxyl radical formation in patient cells was increased over 2–10-fold under basal conditions, and up to 20-fold after menadione or doxorubicin treatment compared with normal cells. We also found an overproduction of aldehydes in patient cells both under basal conditions and after treatment. Both hydroxyl radicals and toxic aldehydes such as hexanal, 4-hydroxynon-2-enal, and malondialdehyde were elevated in cells from patients with three types of complex I deficiency. In contrast, acyloins, the less toxic conjugated products of pyruvate and saturated aldehydes, were lower in the patient cells. Our data provide direct evidence for the first time that complex I deficiency is associated with excessive production of hydroxyl radicals and lipid peroxidation. The resultant damage may contribute to the early onset of cardiomyopathy and cataracts and death in early infancy in affected patients with this disease. (J. Clin. Invest. 1997. 99:2877– 2882.) Key words: complex I deficiency • cardiomyopathy • cataracts • hydroxyl radicals • lipid peroxidatio

Mean (± SEM) cord and maternal plasma folate concentrations at the time of delivery in alcohol-abusing women and controls.

<p>*p<0.05 for a two-tailed paired t-test. **p<0.05 for a two-tailed independent t-test.</p

The transport proteins present on the syncytiotrophoblast that are involved in the transfer of folate to the fetal circulation.

<p>The transport proteins present on the syncytiotrophoblast that are involved in the transfer of folate to the fetal circulation.</p

Scatter-plot of the fetal to maternal (F∶M) folate ratios as measured in cord blood and maternal blood, respectively, at the time of delivery.

<p>Scatter-plot of the fetal to maternal (F∶M) folate ratios as measured in cord blood and maternal blood, respectively, at the time of delivery.</p

Corresponding maternal and fetal folate concentrations at the time of delivery in pregnancies with (A) heavy alcohol exposure and (B) in controls.

<p>Corresponding maternal and fetal folate concentrations at the time of delivery in pregnancies with (A) heavy alcohol exposure and (B) in controls.</p