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Copyright of Revue de Stomatologie & de Chirurgie Maxillo-Faciale is the property of Masson SPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Decreased baroreflex sensitivity (BRS) is a prognostic marker in essential hypertension. Animal experiments suggest that decreased BRS is related to increased oxidative stress. Our study was aimed at testing whether oxidative stress, estimated by isoprostane 15-F2t-IsoP urinary levels, is correlated to BRS variation in healthy subjects as well as in patients suffering from essential hypertension. Urinary 15-F2t-IsoP levels and BRS were evaluated in two groups of subjects: healthy volunteers (n=64) and patients with untreated mild-to-moderate hypertension (n=33). Data were analysed in 61 and 31 subjects, respectively, BRS analysis being impossible in three and two subjects, respectively. 15-F2t-IsoP levels were measured using gas chromatography/mass spectrometry. BRS was measured using the sequence method [PS+/RR+ and PS-/RR-] and crossspectral analysis (CSP) (MF gain) at rest, lying down. No significant correlation was found between basal urinary 15-F2t-IsoP levels and BRS (sequence method and CSP) in either healthy controls or hypertensive patients. Our study shows that oxidative stress is not involved in interindividual variations of BRS in healthy subjects and patients suffering from mild-to-moderate hypertensionJournal of Human Hypertension (2004) 18, 517-521. doi:10.1038/sj.jhh.1001684 Published online 12 February 2004 [ABSTRACT FROM AUTHOR]

Purpose: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS., Methods: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h)., Results: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy., Conclusions: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS., Trial Registration: www.clinicaltrials.gov (NCT01326143).

The ability of cells to sustain mechanical stress is largely modulated by the cytoskeleton. We present a new application of optical tweezers to study cell's mechanical properties. We trap a fibronectin-coated bead attached to an adherent H4II-EC3 rat hepatoma cell in order to apply the force to the cell surface membrane. The bead position corresponding to the cell's local mechanical response at focal adhesions is measured with a quadrant detector. We assessed the cell response by tracking the evolution of the equilibrium force for 40 cells selected at random and selected a temporal window to assess the cell initial force expression at focal adhesions. The mean value of the force within this time window over 40 randomly selected bead∕cell bounds was 52.3 pN. Then, we assessed the responses of the cells with modulation of the cytoskeletons, namely the ubiquitous actin-microfilaments and microtubules, plus the differentiation-dependent keratin intermediate filaments. Notably, a destabilization of the first two networks led to around 50 and 30% reductions in the mean equilibrium forces, respectively, relative to untreated cells, whereas a loss of the third one yielded a 25% increase. The differences in the forces from untreated and treated cells are resolved by the optical tweezers experiment.

The ability of adherent cells to sense and adapt to a mechanical stress generated at focal adhesions (FAs) largely occurs through the integrin-mediated interaction between the cytoskeleton, namely actin microfilaments, and extracellular matrix elements, like fibronectin. Here we assessed the contribution of keratin 8 and 18 (K8/K18) intermediate filaments (IFs) in simple epithelial cells in response to a mechanical stress applied on integrins at FAs. To this end, we used monolayer cultures of K8-knockdown H4-II-E-C3 (shK8b1) rat hepatoma cells and their K8/K18-containing counterparts (H4ev). The stress was generated with a laser tweezers mediated force applied on a fibronectin-coated polystyrene bead attached to integrins alpha5/beta1 forming FAs. Measurement of the bead displacement allowed assessment of the viscoelastic response at FAs and the associated surface membrane stiffness. Notably, the loss of K8/K18 IFs in shK8b1 cells revealed an immediate reduction in bead displacements characteristic of a sudden increased in the FA elastic stiffness, incompatible with the K8/K18 IF intrinsic viscoelastic features, but in line with an induced perturbation of the mechanotransduction signals triggered at integrins. In addition, actin microfilament disruption, and to a lesser extent microtubule disruption, led to prominent decreases in the elastic stiffness of FAs, thus identifying actin-MFs and MTs as modulators of the time-dependent FA stiffening in both H4ev cells and shK8b1 cells, in response to mechanical stress. On technical ground, the laser tweezers offer a tool of choice to delineate the K8/K18 IF-mediated modulation of cytoskeletal versus signaling activities at FAs in epithelial cells in response to mechanical stress.

Objective: Diabetes mellitus is associated with inflammatory state and increased cardiovascular mortality. Leukotrienes are arachidonic acid metabolites derived from the 5-lipoxygenase pathway that possess vasoactive, chemotactic and proinflammatory properties. The aim of this study was to evaluate (1) the urinary excretion of leukotriene E4 (LTE4) in type 1 diabetic subjects and healthy volunteers and (2) the influence of glycemic control attested by HbA(1C) on LTE4 excretion., Methods and Results: Urinary excretion of LTE(4), measured by liquid chromatography-tandem mass spectrometry, was significantly (P=0.033) increased in diabetic patients (median [10th-90th percentiles]: 42.1 pg/mg creatinine [16.7-71.4], n=34), compared to healthy subjects (25.5 pg/mg creatinine [13.9-54.1], n=28). Subgroup analysis indicated a trend towards increased LTE4 excretion in patients with poor glycemic control [(HbA(1C)> or =9% or plasma glucose >18 mmol/L): 43.3 pg/mg creatinine [21.6-70.5], n=14], whereas no difference was observed between patients with good metabolic control [(HbA(1C)< or =7.5%): 36.4 pg/mg creatinine [15.8-83.4], n=20] and healthy subjects., Conclusions: This study suggested that increased LTE4 excretion in type 1 diabetic state might reflect systemic activation of the 5-lipoxygenase pathway. It could be a determinant of underlying inflammatory state and vascular disease.

Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39C[A+1166C] and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.

This double blind randomized controlled trial was designed to investigate whether short-term vitamin E treatment at doses of 500 and 1000 mg/day, compared to placebo, decreased urinary F(2)-isoprostanes and improved the microvascular perfusion after cold exposure in patients suffering from SSc. Thirty-three eligible patients were randomly assigned in a 1.3:1:1 ratio to receive placebo, vitamin E 500 mg, or vitamin E 1000 mg daily for 3 weeks. Clinical examination, analysis of plasma vitamin E, urinary F(2)-isoprostane levels and a whole body cooling test were performed at baseline and after a 3-week period of treatment. Urinary 15-F(2t)-IsoP levels and cutaneous blood flow variation in response to cold did not significantly differ before versus after treatment in any group. Furthermore, no difference was found between groups after 3 weeks of treatment. We show that 3-week vitamin E treatment at doses of 500 or 1000 mg/day neither decreases the basal rate of lipid peroxidation nor improves microvascular perfusion after cold exposure. These data does not support the need for phase III clinical trials to test efficacy of vitamin E in SSc.

In contrast with the huge amount of experimental data available, only few and somewhat unconvincing clinical studies support the hypothesis that oxidative stress is involved in the early stages of essential hypertension in humans. Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of 15-F(2t)-IsoP in the early stages of essential hypertension, using gas chromatography/mass spectrometry, by comparing 30 patients with never-treated mild-to-moderate hypertension with 30 gender- and age-paired healthy controls. Urinary 15-F(2t)-IsoP levels were not significantly different in hypertensive patients (69+/-36 pmol/mmol creatinine) compared with controls (75+/-34 pmol/mmol creatinine, 95% confidence intervals on differences: -23 to 13). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and age, low-density lipoprotein cholesterol, glucose, clinical pulse pressure, carotid intima-media thickness, left ventricular mass index, or aortic pulse wave velocity. In conclusion, this study shows that lipid peroxidation is not increased in never-treated mild-to-moderate hypertension. This suggests that oxidative stress is not implicated in the pathogenesis of human essential hypertension, at least in the early stages.

Objective: F2-isoprostanes are free radical-dependent arachidonic acid metabolites that are used as clinical markers of lipid peroxidation in systemic sclerosis (SSc) and other microvascular diseases. The objectives of this study were to determine whether the basal urinary levels of F2-isoprostane in SSc patients differ from those in patients with primary Raynaud's phenomenon (RP) and to investigate whether F2-isoprostane formation correlates with the cutaneous microvascular perfusion decrease following cold exposure in SSc patients, patients with primary RP, and healthy controls., Methods: Eleven women with RP secondary to SSc, 11 women with primary RP, and 11 healthy women were exposed to decreasing room temperature, from 25 degrees C to 15 degrees C, for 40 minutes. Urine samples were obtained before and after the test for gas chromatography/electronic impact mass spectrometry quantification of 15-F(2t)-isoprostane (15-F(2t)-IsoP; also called isoprostaglandin F(2alpha) type III). Cutaneous blood flow was monitored using a laser Doppler perfusion imager., Results: The mean +/- SEM urinary 15-F(2t)-IsoP levels at baseline in SSc patients (178 +/- 32 pmoles/mmole of creatinine) were 1.9 times higher than those in healthy controls (95 +/- 11 pmoles/mmole of creatinine) and 1.7 times higher than those in patients with primary RP (107 +/- 19 pmoles/mmole of creatinine) (P < 0.05 for controls and patients with primary RP versus SSc patients). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and the temperature or cutaneous blood flow decrease in response to the whole-body cooling. Furthermore, the 15-F(2t)-IsoP response to the cooling test was not correlated with the cutaneous blood flow decrease., Conclusion: Lipid peroxidation is increased in SSc patients, but not in patients with primary RP. Cold exposure leads to a significant but small increase in 15-F(2t)-IsoP levels that is independent of the cutaneous blood flow decrease. F2-isoprostane quantification may be an interesting pharmacologic tool for monitoring responses to antioxidant treatment in SSc patients.

1. Among the F(2)-isoprostanes, the 15- and the 5-series are currently used as markers of lipid peroxidation in vascular diseases. 15-F(2t)-IsoP (also named iPF(2 alpha)-III) exerts a vasoconstriction in most vessels, whereas no data is available concerning 5-F(2t)-IsoP (also named iPF(2 alpha)-VI), which is more abundant in plasma. 2. The aim of this study was to determine whether 5-F(2t)-IsoP possess any vascular effects on various vessels including the isolated rat thoracic aorta, the human internal mammary artery and the saphenous vein. 3. In organ baths, 5-F(2t)-IsoP and its 5-epimer did not affect the basal tone of any vessel, unlike 15-F(2t)-IsoP. These compounds possessed no antagonist effects on 15-F(2t)-IsoP-induced contractions, No dilator effect was observed in comparison with sodium nitroprusside and acetylcholine on the rat aorta. 4. In conclusion, we show that unlike 15-F(2t)-IsoP, 5-F(2t)-IsoP and its 5-epimer possess no vasomotor effects and as such are unlikely to be involved in the pathogenesis of vascular diseases. Further studies are required to test whether these mediators may have effects on systems not being measured in the current study.

Objectives: Reactive oxygen metabolites have been suggested to participate in the pathogenesis of Crohn's disease, but the evidence supporting this contention in vivo is incomplete. Isoprostaglandin F2alpha type III (iPF2alpha-III, or 15-F2t-IsoP) is a prostaglandin F2alpha isomer produced in vivo by free radical-catalyzed peroxidation of arachidonic acid. We aimed to investigate urinary iPF2alpha-III concentrations as an index of lipid peroxidation in 23 patients with Crohn's disease compared with 23 healthy controls, and to test whether lipid peroxidation correlates to clinical relapse and inflammation., Methods: Urinary iPF2alpha-III was measured by gas chromatography/electronic impact mass spectrometry., Results: Urinary iPF2alpha-III concentrations were significantly higher in patients with Crohn's disease than in healthy controls (median [range] = 130 [38-622] vs 91 [35-152] pmol/mmol of creatinine, respectively; p < 0.01). There was a trend toward significance for patients with clinical relapse versus patients with clinical remission (median [range] = 155 [38-622] vs 96 [64-253] pmol/mmol of creatinine, respectively; p = 0.09). A significant correlation was found between urinary iPF2alpha-III and plasma C-reactive protein concentrations, suggesting a link between lipid peroxidation and inflammation., Conclusion: This study provides evidence of increased lipid peroxidation in patients suffering from Crohn's disease, especially in patients with clinical relapse. iPF2alpha-III quantification has to be investigated as a prognosis biomarker in patients suffering from Crohn's disease.

Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of isoprostaglandin F(2alpha) type III (iPF(2alpha)-III), an F(2)-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF(2alpha)-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF(2alpha)-III levels were measured by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were investigated for response to inhaled NO challenge. Urinary iPF(2alpha)-III levels in PHT patients (225 +/- 27 pmol/mmol creatinine) were 2.3 times as high as in controls (97 +/- 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial pressure variation and the pulmonary vascular resistance variation in response to inhaled NO were correlated to basal iPF(2alpha)-III levels. This study shows that oxidative stress is increased in patients with pulmonary hypertension. Furthermore, iPF(2alpha)-III levels inversely correlate to pulmonary vasoreactivity. These observations are consistent with the hypothesis that free radical generation is involved in PHT pathogenesis.

F2-isoprostanes are stable lipid peroxidation products of arachidonic acid and their quantification provides a novel approach to the assessment of oxidative stress in vivo. F2-isoprostanes are present in increased amounts in adult hypercholesterolemia, but no data exist concerning children. We investigated urinary isoprostaglandin F2, type III production as an index of lipid peroxidation in 15 children presenting with type IIa hypercholesterolemia (serum total cholesterol, 290 [SD +/- 70] mg/dl; low-density lipoprotein cholesterol, 210 [SD +/- 90] mg/dl) compared with 15 sex- and age-paired control children (serum total cholesterol, 160 [SD +/- 20] mg/dl). Urinary levels of isoprostaglandin F2alpha type III were measured by gas chromatography mass spectrometry. Urinary concentrations did not differ significantly in hypercholesterolemic children compared with control children (84.7 [SD +/- 37] vs. 96 [SD +/- 35] pmol/mmol creatinine, respectively). No significant correlation was found with total cholesterol, low-density-lipoprotein and high-density-lipoprotein cholesterol, and apolipoprotein B and A1 serum levels. F2-isoprostane urinary levels in children with type IIa hypercholesterolemia do not differ from those of age- and sex-matched control children and are not correlated to blood lipid parameters, suggesting that hypercholesterolemia is not associated with increased lipid peroxidation in childhood.

Buprenorphine, which is used in France as a substitution drug for opioid addiction, is widely abused, and several fatal cases have been reported. In order to confirm a recent intoxication or to establish retrospectively chronic abuse, a simple and reliable gas chromatographic-mass spectrometric method was developed and validated for quantitation of buprenorphine and its active metabolite norbuprenorphine in urine and hair. Two milliliters of urine or 50 mg of pulverized hair was submitted to a pretreatment (enzymatic hydrolysis for urine and decontamination with dichloromethane followed by incubation in 0.1 M HCI for hair). Buprenorphine-d4 was chosen as the internal standard. Selective solid-phase extraction with Bond Elut Certify columns provided recoveries higher than 85% for urine and 43% for hair. By using a mixture of MSTFA/TMSIM/TMCS (100:2:5), buprenorphine and norbuprenorphine produced stable silylated derivatives. The detection was carried out with a quadrupole mass detector working in El selected ion monitoring mode. Ions at m/z 450 and 468 were chosen for the quantitation of buprenorphine and norbuprenorphine, respectively (m/z 454 was used for the internal standard). Limits of quantitation were 0.25 and 0.20 ng/mL, respectively, for buprenorphine and norbuprenorphine in urine and 0.005 ng/mg for the two compounds in hair. Calibration curves were linear from 0 to 50 ng/mL in urine and from 0 to 0.4 ng/mg in hair. Between-day and within-day precisions were less than 8.4% in hair and 6.1% in urine for both molecules in all cases. This method was applied to urine and hair samples collected from patients in a withdrawal treatment program and demonstrated its good applicability in routine analysis and its benefit for clinicians. This technique, which requires instruments already available to many toxicology laboratories, offers an attractive alternative to more sophisticated techniques.