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Although obesity-related cardiovascular disease and hypoxia are associated with erectile dysfunction, little is known about the direct effects of hypoxia on penile arteries. In the present study, the effects of acute hypoxia (P[O.sub.2] = ~10 Torr, 20 min) were investigated in isolated penile arteries to determine the influence of endothelium removal, nitric oxide (NO) synthase (NOS), cyclooxygenase (COX), NADPH oxidase, changes in reactive oxygen species (ROS), and a high-fat diet. Hypoxia-relaxed penile arteries contracted with phenylephrine by ~50%. Relaxation to hypoxia and acetylcholine was reduced by endothelium removal and by inhibition of NOS ([N.sup.[omega]]-nitro-L-arginine) and COX (indomethacin) but was enhanced by Tempol and by NADPH oxidase inhibition with apocynin and gp91ds-tat. Basal superoxide levels detected by lucigenin chemiluminescence were reduced by Tempol and gp91ds-tat and were enhanced by NOS blockade. Hypoxic relaxant responses were enhanced by catalase and ebselen. Exogenous peroxide evoked relaxations of penile arteries, which were partially inhibited by endothelium removal and by the inhibition of COX and extracellular signal-regulated mitogen-activated protein kinase (MAPK) but enhanced by p38 MAPK blockade. The NO-dependent component of relaxation to hypoxia was impaired in penile arteries from high-fat diet-fed, obese rats associated with increased superoxide production. Thus hypoxic relaxation of penile arteries is partially mediated by endothelial NO in a manner that is normally attenuated by endogenous ROS production. Obesity further increases superoxide production and impairs the influence of NO. Therefore, cardiovascular disease involving decreased NO bioavailability and/or enhanced ROS generation may contribute to erectile dysfunction through impairing the relaxation of penile arteries to hypoxia. diet-induced obesity; hypoxia; penile vascular regulation; superoxide doi: 10.1152/ajpheart.00382.2010.

Protein kinase C (PKC) stimulation of NAD(P)H oxidases (Nox) is an important component of multiple vascular disease processes; however, the relationship between oxidase activation and the regulation of vascular smooth muscle contraction by PKC remains poorly understood. Therefore, we examined the signaling cascade of PKC-elicited Nox activation and the role of superoxide and hydrogen peroxide in mediating PKC-induced vascular contraction. Endothelium-denuded bovine coronary arteries showed a PKC-dependent basal production of lucigenin (5 [micro]M)-detected Nox oxidase-derived superoxide, which was stimulated fourfold by PKC activation with 10 [micro]M phorbol 12,13-dibutyrate (PDBu). PDBu appeared to increase superoxide generation by Nox2 through both [p47.sup.phox] and peroxide-dependent Src activation mechanisms based on the actions of inhibitors, properties of Src phosphorylation, and the loss of responses in aorta from mice deficient in Nox2 and [p47.sup.phox]. The actions of inhibitors of contractile regulating mechanisms, scavengers of superoxide and peroxide, and responses in knockout mouse aortas suggest that a major component of the contraction elicited by PDBu appeared to be mediated through peroxide derived from Nox2 activation stimulating force generation through Rho kinase and calmodulin kinase-II mechanisms. Superoxide generated by PDBu also attenuated relaxation to nitroglycerin. Peroxide-derived from Nox2 activation by PKC appeared to be a major contributor to the thromboxane [A.sub.2] receptor agonist U46619 (100 nM)-elicited contraction of coronary arteries. Thus a [p47.sup.phox] and Src kinase activation of peroxide production by Nox2 appears to be an important contributor to vascular contractile mechanisms mediated through activation of PKC. hydrogen peroxide; NADPH oxidase; protein kinase C; Src kinases; coronary artery

The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resveratrol treatment. The smoking-induced upregulation of inflammatory markers (ICAM-1, inducible nitric oxide synthase, IL-6, and TNF-[alpha])in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF-[kappa]B activation and inflammatory gene expression in CAECs. In CAECs, the aforementioned protective effects of resveratrol were abolished by knockdown of SIRT1, whereas the overexpression of SIRT1 mimicked the effects of resveratrol. Resveratrol treatment of rats protected aortic endothelial cells against cigarette smoking-induced apoptotic cell death. Resveratrol also exerted antiapoptotic effects in CSE-treated CAECs, which could be abrogated by knockdown of SIRT1. Resveratrol treatment also attenuated CSE-induced DNA damage in CAECs (comet assay). Thus resveratrol and SIRT1 exert antioxidant, anti-inflammatory, and antiapoptotic effects, which protect the endothelial cells against the adverse effects of cigarette smoking-induced oxidative stress. The vasoprotective effects of resveratrol will likely contribute to its anti-aging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging. tobacco; polyphenol; stroke; inflammation; apoptosis; vascular aging; sirtuin 1

Monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) in rats is preceded by an inflammatory response, progressive endothelial cell membrane disruption, reduction in the expression of caveolin-1, and reciprocal activation of STAT3 (PY-STAT3). Superoxide and NF-KB have been implicated in PAH. To evaluate the role of caveolin-1, PY-STAT3 activation, and superoxide in PAH, MCT-injected rats were treated daily with pyrrolidine dithiocarbamate (PDTC; starting on days 1, 3, and 14 x 2 wk), an inhibitor of inflammation and NF-[kappa]B activation. Hemodynamic data, the expression of inhibitory (I)-[kappa]B[alpha], caveolin-1, and Tie2 (a membrane protein), activation of PY-STAT3 and NF-[kappa]B, and superoxide chemiluminescence were examined. Rats developed progressive PAH at 2 wk post-MCT. There was progressive reduction in the expression of caveolin-1, Tie2, and activation of PY-STAT3 in the lungs. Reduction in I-[kappa]B[alpha] expression was present at 2 and 4 wk post-MCT. Superoxide chemiluminescence and NF-[kappa]B activation were observed only at 2 wk post-MCT and both decreased by 4 wk post-MCT despite progressive PAH. PDTC (starting on days 1 and 3) rescued caveolin-1 and Tie2, reversed MCT-induced PYSTAT3 activation, and attenuated PAH. In addition, PDTC restored I-[kappa]B[alpha] expression and reduced superoxide chemiluminescence at 2 wk but did not inhibit NF-[kappa]B activation despite attenuation of PAH. PDTC had no effect on established PAH. Increased superoxide chemiluminescence and NF-[kappa]B activation appear to be a transient phenomenon in the MCT model. Thus the disruption of endothelial cell membrane integrity resulting in caveolin-I loss and reciprocal activation of PY-STAT3 plays a key role in the MCT-induced PAH. caveolin-l; inhibitory [kappa]B[alpha]; inflammation; PY-STAT3; Tie2

Hyperglycemia increases glucose metabolism via the polyol pathway, which results in elevations of intracellular sorbitol concentration. Thus we hypothesized that elevated level of sorbitol contributes to the development of hyperglycemia-induced dysfunction of microvessels. In isolated, pressurized (80 mmHg) rat gracilis muscle arterioles (~150 [micro]m), high glucose treatment (25 raM) induced reduction in flow-dependent dilation (from maximum of 39 [+ or -] 2% to 15 [+ or -] 1%), which was significantly mitigated by an aldose reductase inhibitor, zopolrestat (maximum 27 [+ or -] 2%). Increasing doses of sorbitol ([10.sup.10]-[10.sup.-4] M) elicited dose-dependent constrictions (maximum 22 [+ or -] 3%), which were abolished by endothelium removal, a prostaglandin [H.sub.2]/thromboxane [A.sub.2] ([PGH.sub.2]/[TXA.sub.2]) receptor (TP) antagonist SQ-29548, or superoxide dismutase (SOD) plus catalase (CAT). Incubation of arterioles with sorbitol ([10.sup.-7] M) reduced flow-dependent dilations (from maximum of 39 [+ or -] 2% to 20 [+ or -] 1.5%), which was not further affected by inhibition of nitric oxide synthase by [N.sup.[omega]]-nitro-L-arginine methyl ester but was prevented by SOD plus CAT and mitigated by SQ-29548. Nitric oxide donor sodium nitroprusside-induced ([10.sup.-9]-[10.sup.-6] M) dilations were also decreased in a SQ-29548 and SOD plus CAT-reversible manner, whereas adenosine dilations were not affected by sorbitol exposure. Sorbitol significantly increased arterial superoxide production detected by lucigenin-enhanced chemiluminescence, which was inhibited by SOD plus CAT. Sorbitol treatment also increased arterial formation of 3-nitrotyrosine. We suggest that hyperglycemia by elevating intracellular sorbitol induces oxidative stress, which interferes with nitric oxide bioavailability and promotes [PGH.sub.2]/[TXA.sub.2] release, both of which affect regulation of vasomotor responses of arterioles. Thus increased activity of the polyol pathway may contribute to the development of microvascular dysfunction in diabetes mellitus. aldose reductase; sorbitol; flow-dependent dilation; oxidative stress; prostaglandin [H.sub.2]; thromboxane [A.sub.2]; nitric oxide

Although the cardiovascular morbidity and mortality induced by cigarette smoking exceed those attributable to lung cancer, the molecular basis of smoking-induced vascular injury remains unclear. To test the link between cigarette smoke, oxidative stress, and vascular inflammation, rats were exposed to the smoke of five cigarettes per day (for 1 wk). Also, isolated arteries were exposed to cigarette smoke extract (CSE; 0 to 40 [micro]g/ml, for 6 h) in organoid culture. We found that smoking impaired acetylcholine-induced relaxations of carotid arteries, which could be improved by the NAD(P)H oxidase inhibitor apocynin. Lucigenin chemiluminescence measurements showed that both smoking and in vitro CSE exposure significantly increased vascular 02' production. Dihydroethidine staining showed that increased [O.sub.2].sub.*.sup.-] generation was present both in endothelial and smooth muscle cells. CSE also increased vascular [H.sub.2][O.sup.2] production (dichlorofluorescein fluorescence). Vascular mRNA expression of the proinflammatory cytokines IL-1[beta], IL-6, and TNF-[beta] and that of inducible nitric oxide synthase was significantly increased by both smoking and CSE exposure, which could be prevented by inhibition of NAD(P)H oxidase (diphenyleneiodonium and apocynin) or scavenging of [H.sub.2]]O.sub.2]. In cultured endothelial cells, CSE elicited NF-[kappa]B activation and increased monocyte adhesiveness, which were prevented by apocynin and catalase. Thus we propose that water-soluble components of cigarette smoke (which are likely to be present in the bloodstream in vivo in smokers) activate the vascular NAD(P)H oxidase. NAD(P)H oxidase-derived [H.sub.2][O.sub.2] activates NF-[kappa]B, leading to proinflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis, especially if other risk factors are also present. tobacco; oxidative stress; stroke; plaque development; cytokine; arteriosclerosis; endothelial dysfunction

We have previously reported that ANG II stimulation increased superoxide anion ([O.sup.-.sub.2]) through the activation of NAD(P)H oxidase and inhibited nitric oxide (NO)-dependent control of myocardial oxygen consumption (MV[o.sub.2]) by scavenging NO. Our objective was to investigate the role of NAD(P)H oxidase, especially the gp[91.sup.phox] subunit, in the NO-dependent control of MV[o.sub.2]. MV[o.sub.2] in mice with defects in the expression of gp[91.sup.phox] [gp[91.sup.phox](-/-)] was measured with a Clark-type oxygen electrode. Baseline MV[o.sub.2] was not significantly different between wildtype (WT) and gp[91.sup.phox](-/-) mice. Stimulation of NO production by bradykinin (BK) induced significant decreases in MV[o.sub.2] in WT mice. BK-induced reduction in MV[o.sub.2] was enhanced in gp[91.sup.phox](-/-) mice. BK-induced reduction in MV[o.sub.2] in WT mice was attenuated by [10.sup.-8] mol/1 ANG II, which was restored by coincubation with Tiron or apocynin. In contrast to WT mice, BK-induced reduction in MV[o.sub.2] in gp[91.sup.phox](-/-) mice was not altered by ANG II. There was a decrease in lucigenin (5 X [10.sup.-6] mol/1)-detectable [O.sup.-.sub.2] in gp[91.sup.phox] (-/-) mice compared with WT mice. ANG II resulted in significant increases in [O.sup.-.sub.2] production in WT mice, which was inhibited by coincubation with Tiron or apocynin. However, ANG II had no effect on [O.sup.-.sub.2] production in gp[91.sup.phox](-/-) mice. Histological examination showed that the development of abscesses and/or the invasion of inflammatory cells occurred in lungs and livers but not in hearts and kidneys from gp[91.sup.phox](-/-) mice. These results indicate that the gp[91.sup.phox] subunit of NAD(P)H oxidase mediates [O.sup.-.sub.2] production through the activation of NAD(P)H oxidase and attenuation of NO-dependent control of MV[o.sub.2] by ANG II. superoxide anion; bradykinin

Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion ([O.sup.-.sub.2]) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, [O.sup.-.sub.2], inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P < 0.05). Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD. Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS hut increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in [O.sup.-.sub.2]. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase. antioxidant enzymes; extracellular superoxide dismutase; nitric oxide synthase; endothelial dysfunction; superoxide; oxidative stress

The role of mitochondrial manganese-superoxide dismutase (Mn-SOD) in the maintenance of vascular function has not yet been studied. Thus we examined flow- and agonist-induced dilations in isolated mesenteric arteries (~90 [micro]m in diameter) of Mn-SOD heterozygous (Mn-SO[D.sup.+/-]) and wild-type (WT) mice. Increases in flow elicited dilations in all vessels, but the magnitude of the dilation was significantly less in vessels of Mn-SO[D.sup.+/-] mice than in those of WT mice (64 vs. 74% of passive diameter). [N.sup.[omega]]-nitro-L-arginine methyl ester inhibited the dilation in vessels of WT mice but had no effect on vessels of Mn-SO[D.sup.+/-] mice. Tempol or tiron (superoxide scavengers) increased flow-induced dilation in vessels of Mn-SO[D.sup.+/-] mice. Acetylcholine- and sodium nitroprusside-induced, but not adenosine-induced, dilations were also decreased in arteries of Mn-SO[D.sup.+/-] mice. Superoxide levels in the arteries of Mn-SO[D.sup.+/-] mice were significantly increased. Western blot analysis confirmed a 50% reduction of Mn-SOD protein in the vessels of Mn-SO[D.sup.+/-] mice. A 41% reduction in endothelial nitric oxide synthase (eNOS) protein and a 37% reduction in eNOS activity were also found in the vessels of Mn-SO[D.sup.+/-] mice. Whereas there was no difference in eNOS protein in kidney homogenates of WT and Mn-SO[D.sup.+/-] mice, a significant reduction of nitric oxide synthase activity was found in Mn-SO[D.sup.+/-] mice, which could be restored by the administration of tiron. We conclude that an increased concentration of superoxide due to reduced activity of Mn-SOD, which inactivates nitric oxide and inhibits eNOS activity, contributes to the impaired vasodilator function of isolated mesenteric arteries of MnSO[D.sup.+/-] mice. These results suggest that Mn-SOD contributes significantly to the regulation of vascular function. shear stress; endothelial nitric oxide; superoxide distmutase-2

Because systems controlled by basal NAD(P)H oxidase activity appear to contribute to differences in responses of endothelium-removed bovine coronary (BCA) and pulmonary (BPA) arteries to hypoxia, we characterized the Nox oxidases activities present in these vascular segments and how cytosolic NAD(P)H redox systems could be controlling oxidase activity. BPA generated ~60-80% more lucigenin (5 [micro]M) chemiluminescence detectable superoxide than BCA. Apocynin (10 [micro]M), a NAD(P)H oxidase inhibitor, and 6-aminonicotinamide (1 mM), a pentose phosphate inhibitor (PPP), both attenuated (approximately by 50-70%) superoxide detected in BPA and BCA. There was no significant difference in the expression of Nox2 or Nox4 mRNA or protein detected by Western blot analysis. NADPH and NADH increased superoxide in homogenates and isolated microsomal membrane fractions in a manner consistent with BPA and BCA having similar levels of oxidase activity. BPA had 4.2-fold higher levels of NADPH than BCA. The activity and protein levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting PPP enzyme generating cytosolic NADPH, were 1.5-fold higher in BPA than BCA. Thus BPA differ from BCA in that they have higher levels of G6PD activity, NADPH, and superoxide. Because both arteries have similar levels of Nox expression and activity, elevated levels of cytosolic NADPH may contribute to increased superoxide in BPA. glucose-6-phosphate dehydrogenase; lactate; NAD(P)H oxidase; Nox2; Nox4; pentose phosphate pathway.

Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. Art! J Physiol Heart Circ Physiol 286: H2249-H2256, 2004. First published January 29, 2004; 10.1152/ ajpheart.00854.2003.--We hypothesized that aging is characterized by a reduced release of nitric oxide (NO) in response to shear stress in resistance vessels. Mesenteric arterioles and arteries of young (6 too) and aged (24 mo) male Fischer 344 rats were isolated and cannulated. Shear stress (15 dyn/[cm.sup.2])-induced dilation was significantly reduced and shear stress (1, 5, 10, and 15 dyn/[[cm.sup.2])-induced increases in perfusate nitrite were significantly smaller at all shear stress levels in vessels of aged rats. Inhibition of NO synthesis abolished shear stress-induced release of nitrite. Furthermore, shear stress (15 dyn/[cm.sup.2])-induced release of nitrate was significantly higher and total nitrite (nitrite plus nitrate) was significantly lower in vessels of aged rats. Tiron or SOD significantly increased nitrite released from vessels of aged rats, but this was still significantly less than that in young rats. Superoxide production was increased and the activity of SOD was decreased in vessels of aged rats. There were no differences in endothelial NO synthase (eNOS) protein and basal activity or in Cu/Zn-SOD and Mn-SOD proteins in vessels of the two groups, but extracellular SOD was significantly reduced in vessels of aged rats. Maximal release of NO induced by shear stress plus ACh (10[-sup.5]M) was comparable in the two groups, but phospho-eNOS in response to shear stress (15 dyn/[cm.sup.2) was significantly reduced in vessels of aged rats. These data suggest that an increased production of superoxide, a reduced activity of SOD, and an impaired shear stress-induced activation of eNOS are the causes of the decreased shear stress-induced release of NO in vessels of aged rats. endothelium; superoxide; superoxide dismutase

Pentose phosphate pathway (PPP) inhibitors, 6-aminonicotinamide (6-AN) and epiandrosterone (Epi), were employed to examine whether changes in NADP(H) redox regulates contractile force in endothelium-removed bovine coronary arteries (BCAs). 6-AN (0.01-5 mM) or Epi (1-500 [micro]M) elicited dose-dependent relaxation in BCAs contracted with 30 mM KCl, 0.1 [micro]M U-44619, and endothelin-1 but not with phorbol 12,13-dibutyrate, a protein kinase C activator that causes [Ca.sup.2+]-independent contraction. Relaxation to PPP inhibition was associated with oxidation of NADPH and glutathione (GSH). Relaxation to 6-AN was not mediated by [H.sub.2][O.sub.2], because it was not altered by hypoxia or the peroxide scavenger ebselen (100 [micro]M). The thiol reductant DTT (3 mM) attenuated the relaxation to 6-AN and Epi by 30-40%. Inhibition of glycolysis of mitochondrial electron transport did not elicit relaxation in BCAs contracted with 30 mM KCl, suggesting these pathways may not be involved in relaxation elicited by PPP inhibition. High doses of [K.sup.+] channel blockers [e.g., TEA (10 mM) and 4-aminopyridine (10 mM)] only partially inhibited the relaxation to 6-AN. On the basis of changes in the fura-2 fluorescence ratio, 6-AN and Epi appeared to markedly reduce intracellular [Ca.sup.2+]. Thus PPP inhibition oxidizes NADPH and GSH and appears to activate a novel coordination of redox-controlled relaxing mechanisms in BCAs mediated primarily through decreasing intracellular C[a.sup.2+] calcium; redox signaling; vasodilator mechanisms

Compensation of Kerr nonlinearity-induced distortions has been shown to allow for increasing transmission rate and reach, with optical compensation techniques particularly attractive for broadband wavelength-division multiplexed (WDM) scenarios. However, they normally require additional devices within the link, which is particularly challenging for already deployed systems, and even more so for unrepeatered transmission. In this work, we focus on providing lumped optical nonlinearity suppression, either at the transmitter or at the receiver side, based on optical phase conjugation (OPC). The theory to design scaled-down OPC compensation modules is derived, and it allows to move beyond the standard mid-link OPC approach and to explore compensation modules with fibers types not directly linked to the dispersion properties of the transmission link. This design method is then validated both through numerical investigations and experimental demonstrations for a number of systems with a varying degree of complexity. Ultimately, significant performance improvement is shown by employing short OPC-based compensation structures which are carefully designed to match much longer transmission links. [ABSTRACT FROM AUTHOR]

Experiment was conducted to examine the importance of endogenous peroxynitrite (ONOO-) formation in the regulation of bovine pulmonary arteries (BPA) force generation by elevated physiological levels of NO. Exposure of BPA precontracted with 30 mM KCl to -50 nM NO for 2 min resulted in a subsequent prolonged relaxation of KCl-induced force and an increased release of NO. The NO release was reduced after depletion of tissue glutathione with diethyl maleate. During exposure to elevated physiological levels of NO, BPA appear to produce ONOO-.

The superoxide anion generates hydrogen peroxide (H2O2) in response to changes in PO2 in isolated endothelium-removed calf pulmonary arteries. Since the superoxide anion is produced by NADH oxidase, production of H2O2 is dependent on NADH oxidase activity. Under conditions of hypoxia, superoxide anion production is decreased. During reoxygenation, the superoxide anion is overproduced, and in turn, inhibits the formation of H2O2.

Bovine pulmonary arteries pretreated with potassium contracted upon addition of micromolar concentrations of nitrogen dioxide (NO2). Hemoglobin (Hb), methylene blue (MB) and the ionophore LY-83583 inhibited relaxation to NO2 whereas reduced glutathione (GSH) or cysteine enhanced the NO2-induced contractions. Relaxation induced by S-nitro-GSH was inhibited by Hb, MB and LY-83583. It was concluded that NO2 can promote prolonged relaxation of the pulmonary arteries, and that this function is important in the regulation of inflammatory processes.

Throughput optimization of optical communication systems is a key challenge for current optical networks. The use of gain-flattening filters (GFFs) simplifies the problem at the cost of insertion loss, higher power consumption and potentially poorer performance. In this work, we propose a component-wise model of a multi-span transmission system for signal-to-noise ratio (SNR) optimization. A machine-learning based model is trained for the gain and noise figure spectral profile of a C-band amplifier without a GFF. The model is combined with the Gaussian noise model for nonlinearities in optical fibers including stimulated Raman scattering and the implementation penalty spectral profile measured in back-to-back in order to predict the SNR in each channel of a multi-span wavelength division multiplexed system. All basic components in the system model are differentiable and allow for the gradient descent-based optimization of a system of arbitrary configuration in terms of number of spans and length per span. When the input power profile is optimized for flat and maximized received SNR per channel, the minimum performance in an arbitrary 3-span experimental system is improved by up to 8 dB w.r.t. a system with flat input power profile. An SNR flatness down to 1.2 dB is simultaneously achieved. The model and optimization methods are used to optimize the performance of an example core network, and 0.2 dB of gain is shown w.r.t. solutions that do not take into account fiber nonlinearities. The method is also shown to be beneficial for systems with ideal gain flattening, achieving up to 0.3 dB of gain w.r.t. a flat input power profile. [ABSTRACT FROM AUTHOR]

A study was conducted to determine whether diphenyliodonium (DPI), an oxidoreductase, could function as an inhibitor of oxygen production by NADH oxidoreductase in calf pulmonary arterial smooth muscle. The changes in oxygen production were monitored by lucigenin-elicited chemiluminescence in the tissue. The results revealed that DPI inhibits pulmonary arterial smooth muscle tone responses in association with changes in PO2 and O2.

NADH oxidoreductase is the main detected source of O2 production in bovine coronary endothelial cells. Metabolic conditions such as enhanced levels of lactate or hypoxia regulate O2 generation in endothelium by increasing the production of cystolic NADH. Xanthine oxidase, mitochondrial-electron transport and autooxidation processes are subsidiary sources for production of O2 species.

Study of nitric oxide (NO) and nitrosothiol inclusion in relaxation of pulmonary arteries to peroxynitrite (ONOO) indicates that ONOO relaxes vascular tissue through the nitrosylation tissue glutathione (GSH) which releases NO over long time periods. ONOO-regulated nitrosylation synthesizes S-nitrosothiols which are found in blood plasma. The short period of ONOO indicates its functions as a tissue hormone in transcellular signal transduction and as a toxic species in pathophysiology.

Abstract Background Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN) and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV). Methods The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. Results The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p = 0.37). There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had ≥2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. Conclusions Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have developed in the cervical canal.

Abstract Background Different mechanisms of diabetic-induced NO dysfunction have been proposed and central to most of them are significant changes in eNOS function as the rate-limiting step in NO bioavailability. eNOS exists in both monomeric and dimeric conformations, with the dimeric form catalyzing the synthesis of nitric oxide, while the monomeric form catalyzes the synthesis of superoxide (O2-). Diabetic-induced shifts to decrease the dimer:monomer ratio is thought to contribute to the degradation of nitric oxide (NO) bioavailability. Exercise has long been useful in the management of diabetes. Although exercise-induced increases expression of eNOS has been reported, it is unclear if exercise may alter the functional coupling of eNOS. Methods To investigate this question, Goto-Kakizaki rats (a model of type II diabetes) were randomly assigned to a 9-week running program (train) or sedentary (sed) groups. Results Exercise training significantly (p < .05) increased plantaris muscle cytochrome oxidase, significantly improved glycosylated hemoglobin (sed: 7.33 ± 0.56%; train: 6.1 ± 0.18%), ad improved insulin sensitivity. Exercise increased both total eNOS expression and the dimer:monomer ratio in the left ventricle LV (sed: 11.7 ± 3.2%; train: 41.4 ± 4.7%). Functional analysis of eNOS indicated that exercise induced significant increases in nitric oxide (+28%) production and concomitant decreases in eNOS-dependent superoxide (-12%) production. This effect was observed in the absence of tetrahydrobiopterin (BH4), but not in the presence of exogenous BH4. Exercise training also significantly decreased NADPH-dependent O2- activity. Conclusion Exercise-induced increased eNOS dimerization resulted in an increased coupling of the enzyme to facilitate production of NO at the expense of ROS generation. This shift that could serve to decrease diabetic-related oxidative stress, which should serve to lessen diabetic-related complications.

In this article, a rate-adaptive coded modulation (CM) system combining polar codes and many-to-one probabilistic shaping is constructed and experimentally demonstrated. We propose to control the polar codes using a fraction of bits referred to as pre-set bits. This not only allows to offset the puncturing loss of rate-adaptive polar codes but also provides shaping gains compared to the non-punctured polar codes. Pre-set bits and many-to-one shaping are combined to form a rate-adaptive bit-interleaved CM system. We experimentally evaluate the system performance for 10 × 8-GBd dual polarization 256 quadrature amplitude modulation (QAM) wavelength division multiplexed (WDM) system with various input data rates ranging from 61 to 91 Gbps per carrier. The experimental results demonstrate a 200 km reach increase over a wide range of distances compared to the non-punctured polar codes and punctured polar codes. [ABSTRACT FROM AUTHOR]