Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.     

Properties of permease dimer, a fusion protein containing two lactose permease molecules from Escherichia coli

An engineered fusion protein containing two tandem lactose permease molecules (permease dimer) exhibits high transport activity and is used to test the phenomenon of negative dominance. Introduction of the mutation Glu-325-->Cys into either the first or the second half of the dimer results in a 50% decrease in activity, whereas introduction of the mutation into both halves of the dimer abolishes transport. Lactose transport by permease dimer is completely inactivated by N-ethylmaleimide; however, 40-45% activity is retained after N-ethylmaleimide treatment when either the first or the second half of the dimer is replaced with a mutant devoid of cysteine residues. The observations demonstrate that both halves of the fusion protein are equally active and suggest that each half may function independently. To test the possibility that oligomerization between dimers might account for the findings, a permease dimer was constructed that contains two different deletion mutants that complement functionally when expressed as untethered molecules. Because this construct does not catalyze lactose transport to any extent whatsoever, it is unlikely that the two halves of the dimer interact or that there is an oligomeric interaction between dimers. The approach is consistent with the contention that the functional unit of lactose permease is a monomer.     

Short-term frequency stability of clock generators for multigigahertz rapid-single-flux quantum digital circuits

Superconducting digital systems based on Josephson junctions have generally used a synchronous timing strategy. A master clock signal is used to delimit a data window during which the system changes state and data is transferred from one block to the next. The temporal stability of the clock signal has a profound effect on the performance of rapid single flux quantum (RSFQ) digital systems. In particular, short-term clock fluctuations, or clock jitter, can degrade system performance due to the hazard of timing constraint violations. The successful development of large-scale RSFQ digital systems will require highly stable multigigahertz on-chip clock sources. To meet this need, methods for characterizing and measuring the short-term stability of such sources are required. We identify the relevant figure of merit to characterize and compare various clocks: the cycle-to-cycle standard deviation of the clock periods. We present experimental techniques for the measurement of this figure of merit and apply them to the measurement of jitter in a clock generator used often in RSFQ systems, the ring oscillator. High-frequency phase noise measurements found the jitter of a 9.6-GHz clock to be in the range from 0.6% to 0.36% of the clock period. The measured values of clock jitter fell within the 95% confidence interval of our stochastic circuit simulations. This was sufficient evidence to conclude that thermal noise from the resistors in the circuit may be the dominant source of jitter in the ring oscillator.     

One‐dimensional finite element solution for tall building structures unified plane panels formulation

In a previous paper (Mancini and Savassi, 1999), it was shown that every plane panel, used to brace tall building structures, can be easily and generally approached through the use of the continuous medium technique (CMT) (Albigés and Goulet, 1960). In that paper, following a so‐called local formulation, i.e., by deriving the governing differential equations system of the panel, in terms of u(z) panel horizontal displacement and w_i columns or walls axial displacements, the equivalence (likeness) of formal mathematics, and hence of structural behaviour, between the panel composed by a pair of shear walls associated by lintel beams and another panel formed by the plane association, by pinned horizontal bars, of one shear wall and one single bay frame, was also shown. In both cases, axial deformations due to axial forces on vertical members were taken into account. In this paper, confirming those conclusions, but now following a global formulation (i.e., considering the total potential energy of each panel: strain energy plus applied load potentials), the mathematical equivalence between those two types of plane panels is again revealed by comparison of their two total potential energy analytical expressions. Additionally, based on that variational approach, the one‐dimensional finite element formulation is presented. This enlarges the possibilities of solutions for more general types of panels, like those with variable geometry or loading, without any further difficulty. The procedure, for any type of panel, can be codified in one single computer program, very similar to those used to solve plain continuous beam problems. Copyright © 2004 John Wiley & Sons, Ltd.     

Hematological malignancies with a deletion of 11q23: cytogenetic and clinical aspects. European 11q23 Workshop participants

OBJECTIVE: Using receiver-operating characteristic (ROC) curves, we tried to determine the diagnostic threshold of amniotic fluid index (AFI) that will identify abnormal fetal size (birth weights under 2500 g or at least 4000 g) at 37 weeks or beyond. METHODS: We analyzed prospectively over 2 years all parturients with intact membranes and known AFI in early labor. Patients with the following conditions were excluded: pregestational or gestational diabetes, known anomalies, and preterm labor. Two ROC curves were constructed, and the areas (+/- standard error of the mean [SE]) under the curves were calculated. P < .05 was considered significant. RESULTS: Of the 1038 subjects meeting study criteria, 3.6% and 11.5% gave birth to infants who were small for gestational age (SGA) or macrosomic, respectively. Overall, 28.7% had oligohydramnios (AFI at most 5.0 cm) and 3.6% had hydramnios (AFI at least 24.0 cm). Small for gestational age was more common in patients with AFI at most 5.0 cm (6.4%) than in those with adequate fluid (AFI 5.1-23.9; 2.5%), or hydramnios (2.7%; P = .012). Macrosomic newborns were less likely to be born to women with oligohydramnios (7.7%) than to those with adequate amniotic fluid (13.1%) or hydramnios (13.5%). Areas under ROC curves are not significantly different from the area under the nondiagnostic line, indicating that AFI (0-34 cm) cannot differentiate between newborns under 2500 g and at or over 2500 g or under 4000 and at or more 4000 g. CONCLUSION: Intraparterium AFI appears to be a poor screening test to identify risk for delivery of SGA or macrosomic fetus.     

Rapid infusion system for neurosurgical treatment of massive intraoperative hemorrhage

Using an illustrative case of severe closed head injury that resulted in a posterior fossa epidural hematoma (EDH) and supratentorial epidural/subdural hematomas (SDH), the massive blood losses associated with operative repair of the torn sigmoid sinus and the significant fluid losses associated with refractory diabetes insipidus were treated by the intraoperative use of the Rapid Infusion System (RIS, Haemonetics). The RIS can rapidly infuse warm blood, crystalloid, or colloid at rates up to 1.5 L/min, thereby limiting the commonly associated hypotension, hypothermia, and coagulopathies. During the suboccipital craniectomy for evacuation of the EDH and repair of the sigmoid sinus, the patient required 18 units of blood replacement secondary to a large tear in the sigmoid sinus. During a separate craniotomy for evacuation of the SDH, the patient also developed diabetes insipidus, which increased the operative fluid replacement to 39 L. Despite these massive blood and fluid losses, the RIS limited the hypotension to less than 2 min and prevented hypothermia and the frequently associated coagulopathies. When used in a neurosurgical setting associated with massive blood and/or fluid losses, the RIS accomplishes three important objectives: (1) rapid infusion of intravenous fluids for maintaining perfusion pressure, (2) rapid warming of fluids despite high intravenous infusion rates of cold crystalloids, thereby preventing intraoperative hypothermia, and (3) continuous monitoring of infusion rates and totals.