VIP expression in vessels of the vaginal wall: relationship with estrogen status

Objective Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall. Methods Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-alpha) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-alpha scores. Results The vaginal walls of premenopausal women had significantly higher ER-alpha scores than those of menopausal women (premenopausal group, 3.6 +/- 2.2; menopausal group, 1.4 +/- 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99). Conclusion Levels of ER-alpha and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

Leaf level VOC emissions of single plants from Amazonian and Mediterranean ecosystems: Ontogeny and flooding as stress factor for VOC emissions

Die Vegetation ist die wichtigste Quelle von organischen flüchtigen Verbindungen (auf Englisch volatile organic compounds,VOCs), die einen bemerkenswerten Einfluss auf der Chemie und Physik der Atmosphäre haben. VOCs beeinflussen die oxidative Kapazität der Atmosphäre und tragen zu der Bildung und zum Wachstum von sekundären organischen Aerosolen bei, welche einerseits eine Streuung und Reflektierung der Energie verursachen und andererseits sich an der Bildung und Entwicklung von Wolken beteiligen. Ziel dieser Arbeit war die Beschreibung und der Vergleich von VOC Emissionen aus Pflanzen aus zwei verschiedenen Ökosystemen: Mediterranes Ökosystem und Tropisches Ökosystem. Für diese Aufgabe wurden gewöhnliche Pflanzen von beiden Ökosystemen untersucht. Siebzehn Pflanzenspezies aus der Mittelmeergebiet, welches bekannt ist für seine Vielfalt an VOC emittierenden Pflanzen, wurden in die Untersuchungen einbezogen. Im Gegensatz zum mediterranen Ökosystem sind nur wenig Information verfügbar über VOC Emissionen aus Blättern tropischer Baumspezies. Vor diesem Hintergrund wurden sechsundzwanzig Baumspezies aus verschiedenen Ökotypen des Amazonasbeckens (Terra firme, Várzea und Igapó) wurden auf VOC Emissionen auf Blattebene mit einem Küvetten-System untersucht. Analysen von flüchtigen organischen Verbindungen wurden online mit PTR-MS und offline mittels Sammlung auf entsprechenden Adsorbern (Kartuschen) und nachfolgender GC-FID Analyse untersucht. Die höchsten Emissionen wurden für Isoprene beobachtete, gefolgt durch Monoterpene, Methanol und Aceton. Die meisten Mittelmeer Spezies emittierten eine hohe Vielfalt an Monoterpenspezies, hingegen zeigten nur fünf tropische Pflanzenspezies eine Monoterpene mit einen sehr konservativen Emissionsprofil (α-Pinen>Limonen>Sabinen >ß-Pinen). Mittelmeerpflanzen zeigten zusätzlich Emissionen von Sesquiterpenen, während bei der Pflanzen des Amazonas Beckens keine Sesquiterpenemissionen gefunden wurden. Dieser letzte Befund könnte aber auch durch eine niedrigere Sensitivität des Messsystems während der Arbeiten im Amazonasgebiet erklärt werden. Zusätzlich zu den Isoprenoidemissionen waren Methanolemissionen als Indikator für Wachtumsvorgänge sehr verbreitet in den meisten Pflanzenspezies aus tropischen und mediterranen Gebieten. Einige Pflanzenspezies beider Ökosystemen zeigten Acetonemissionen. rnrnVOC Emissionen werde durch eine große Vielfalt an biotischen und abiotischen Faktoren wie Lichtintensität, Temperatur, CO2 und Trockenheit beeinflusst. Ein anderer, öfter übersehener Faktor, der aber sehr wichtig ist für das Amazonas Becken, ist die regelmäßige Überflutung. In dieser Untersuchung wir fanden heraus, dass am Anfang einer Wurzelanoxie, die durch die Überflutung verursacht wurde, Ethanol und Acetaldehyd emittiert werden können, vor allem in Pflanzenspezies, die schlechter an eine unzureichende Sauerstoffversorgung bei Flutung adaptiert sind, wie z.B. Vatairea guianensis. Die Spezies Hevea spruceana, welche besser an Überflutung adaptiert ist, könnte möglicherweise der gebildete Ethanol sofort remetabolisieren ohne es zu emittieren. Nach einer langen Periode einer Überflutung konnte allerdings keine Emission mehr beobachtet werden, was auf eine vollständige Adaptation mit zunehmender Dauer schließen lässt. Als Reaktion auf den ausgelösten Stress können Isoprenoidemissionen ebenfalls kurzfristig nach einigen Tage an Überflutung zunehmen, fallen dann aber dann nach einer langen Periode zusammen mit der Photosynthese, Transpiration und stomatäre Leitfähigkeit deutlich ab.rnrnPflanzen Ontogenese ist anscheinend von Bedeutung für die Qualität und Quantität von VOC Emissionen. Aus diesem Grund wurden junge und erwachsene Blätter einiger gut charakterisierten Pflanzen Spezies aus dem Mittelmeerraum auf VOC Emissionen untersucht. Standard Emissionsfaktoren von Isopren waren niedriger in jungen Blättern als in erwachsene Blätter. Hingegen wurden höhere Monoterpen- und Sesquiterpenemissionen in jungen Blätter einiger Pflanzenspezies gefunden. Dieser Befund deutet auf eine potentielle Rolle dieser VOCs als Abwehrkomponenten gegen Pflanzenfresser oder Pathogene bei jungen Blätter hin. In einigen Fällen variierte auch die Zusammensetzung der Monoterpen- und Sesquiterpenspezies bei jungen und erwachsenen Blättern. Methanolemissionen waren, wie erwartet, höher in jungen Blättern als in ausgewachsenen Blättern, was mit der Demethylierung von Pectin bei der Zellwandreifung erklärt werden kann. Diese Befunde zu Änderungen der Emissionskapazität der Vegetation können für zukünftige Modellierungen herangezogen werden. rn

Sonographic transvaginal bladder wall thickness: Does the measurement discriminate between urodynamic diagnoses?

Measurement of bladder wall thickness (BWT) using transvaginal ultrasound has previously been shown to discriminate between women with confirmed detrusor overactivity and those with urodynamic stress incontinence. Aim of the current study was to determine if vaginally measured BWT correlates with urodynamic diagnoses in a female population.

How should bladder wall thickness be measured? A comparison of vaginal, perineal and abdominal ultrasound

Measurement of bladder wall thickness using transvaginal ultrasound has previously been shown to discriminate between women with diagnosed detrusor overactivity and those with urodynamic stress incontinence. So far, no comparison has been made between abdominal, perineal and vaginal route for the measurement of bladder wall thickness. The aim of this prospective study was to determine if abdominal, perineal and vaginal ultrasound measurements of bladder wall thickness are comparable with each other.

Stress and Strain Adaptation in Load-Dependent Remodeling of the Embryonic Left Ventricle

Altered pressure in the developing left ventricle (LV) results in altered morphology and tissue material properties. Mechanical stress and strain may play a role in the regulating process. This study showed that confocal microscopy, three-dimensional reconstruction, and finite element analysis can provide a detailed model of stress and strain in the trabeculated embryonic heart. The method was used to test the hypothesis that end-diastolic strains are normalized after altered loading of the LV during the stages of trabecular compaction and chamber formation. Stage-29 chick LVs subjected to pressure overload and underload at stage 21 were reconstructed with full trabecular morphology from confocal images and analyzed with finite element techniques. Measured material properties and intraventricular pressures were specified in the models. The results show volume-weighted end-diastolic von Mises stress and strain averaging 50–82% higher in the trabecular tissue than in the compact wall. The volume-weighted-average stresses for the entire LV were 115, 64, and 147Pa in control, underloaded, and overloaded models, while strains were 11, 7, and 4%; thus, neither was normalized in a volume-weighted sense. Localized epicardial strains at mid-longitudinal level were similar among the three groups and to strains measured from high-resolution ultrasound images. Sensitivity analysis showed changes in material properties are more significant than changes in geometry in the overloaded strain adaptation, although resulting stress was similar in both types of adaptation. These results emphasize the importance of appropriate metrics and the role of trabecular tissue in evaluating the evolution of stress and strain in relation to pressure-induced adaptation.

Does bladder wall thickness decrease when obstruction is resolved?

The aim of the current study was to determine if sonographic bladder wall thickness diminishes after symptomatic obstruction is resolved in female patients after stress incontinence surgery.

Stress-induced targeting of molecular chaperones in the yeast Saccharomyces cerevisiae

The eukaryotic stress response is an essential mechanism that helps protect cells from a variety of environmental stresses. Cell death can result if cells are not able to properly adapt and protect themselves against adverse stress conditions. Failure to properly deal with stress has implications in human diseases including neurodegenerative disorders and distinct cancers, emphasizing the importance of understanding the eukaryotic stress response in detail. As part of this response, expression of a battery of heat shock proteins (HSP) is induced, which act as molecular chaperones to assist in the repair or triage of unfolded proteins. The 90-kDa HSP (Hsp90) operates in the context of a multi-chaperone complex to promote the maturation of nuclear and cytoplasmic clients. I have discovered that Hsp90 and the co-chaperone Sba1 accumulate in the nucleus of quiescent Saccharomyces cerevisiae cells in a karyopherin-dependent manner. I isolated nuclear accumulation- defective HSP82 mutant alleles to probe the nature of this targeting event and identified a mutant with a single amino acid substitution (I578F) sufficient to prevent nuclear accumulation of Hsp90 in quiescent cells. Diploid hsp82-I578F cells exhibited pronounced defects in spore wall construction and maturation, resulting in catastrophic sporulation. The mislocalization and sporulation phenotypes were shared by another previously identified HSP82 mutant allele, further linking localization to Hsp90 functional status. Pharmacological inhibition of Hsp90 with macbecin in sporulating diploid cells also blocked spore formation, underscoring the importance of this chaperone in this developmental program. The yeast molecular chaperone Hsp104 is a member of the Hsp100 superfamily of AAA+ ATPases. Unlike the Hsp90 family of chaperones, Hsp104 is not restricted to a specific set of client proteins, but rather assists in reactivating stress-denatured proteins by solubilizing protein aggregates. I have discovered that Hsp104, along with the Hsp70 chaperone, Ssa1, and the sHSP Hsp26 accumulate into RNA processing bodies (P- bodies) and stress granules, sites of mRNA metabolism. I found that Hsp104 recruits both Ssa1 and Hsp26 to P-bodies and that these three chaperones are required for stress granule formation. These findings suggest a possible role for chaperones in mRNA metabolism by aiding in the assembly, disassembly or conversion of these enigmatic mRNP complexes. Taken together, the work presented in this dissertation serves to better understand the eukaryotic stress response by illustrating the importance of subcellular-chaperone localization in key biological processes.

Impact of local endothelial shear stress on neointima and plaque following stent implantation in patients with ST-elevation myocardial infarction: A subgroup-analysis of the COMFORTABLE AMI-IBIS 4 trial.

BACKGROUND Numerous studies have demonstrated an association between endothelial shear stress (ESS) and neointimal formation after stent implantation. However, the role of ESS on the composition of neointima and underlying plaque remains unclear. METHODS Patients recruited in the Comfortable AMI-IBIS 4 study implanted with bare metal stents (BMS) or biolimus eluting stents (BES) that had biplane coronary angiography at 13month follow-up were included in the analysis. The intravascular ultrasound virtual-histology (IVUS-VH) and the angiographic data were used to reconstruct the luminal surface, and the stent in the stented segments. Blood flow simulation was performed in the stent surface, which was assumed to represent the luminal surface at baseline, to assess the association between ESS and neointima thickness. The predominant ESS was estimated in 3-mm segments and was correlated with the amount of neointima, neointimal tissue composition, and with the changes in the underlying plaque burden and composition. RESULTS Forty three patients (18 implanted with BMS and 25 with BES) were studied. In both stent groups negative correlations were noted between ESS and neointima thickness in BMS (P<0.001) and BES (P=0.002). In BMS there was a negative correlation between predominant ESS and the percentage of the neointimal necrotic core component (P=0.015). In BES group, the limited neointima formation did not allow evaluation of the effect of ESS on its tissue characteristics. ESS did not affect vessel wall remodeling and the plaque burden and composition behind BMS (P>0.10) and BES (P>0.45). CONCLUSIONS ESS determines neointimal formation in both BMS and BES and affects the composition of the neointima in BMS. Conversely, ESS does not impact the plaque behind struts irrespective of stent type throughout 13months of follow-up.

Can urethrolysis resolve outlet obstruction related symptoms after Burch colposuspension for stress urinary incontinence?

OBJECTIVE Bladder outlet obstruction may occur after any incontinence surgery and may present as OAB, hesitancy and or the feeling of incomplete emptying. Aim of this study was to analyze the clinical and urodynamical outcome after urethrolysis in patients presenting with various clinical symptoms after Burch colposuspension for stress urinary incontinence. STUDY DESIGN Between January 2005 and December 2014, all patients who presented with symptoms and with bladder outlet obstruction were included. All patients had undergone Burch or Cowan colposuspension for stress urinary incontinence previously. Primary endpoint was the visual analogue scale (VAS) as measurement of patient perceived disease impact. Secondary endpoints were the various domains of the King's Health Questionnaire, urodynamic parameters as detrusor pressure at maximum flow, residual urine and sonographic bladder wall thickness before and six months after intervention. RESULTS Seventy-two female patients were included in this study whereof 42 suffered from urgency and urge incontinence, 20 from hesitancy and/or slow stream, seven from residual urine of more than 100ml and three from a combination of urgency and residual urine. VAS improved significantly (p<0.0001). Quality of life as determined by the King's Health Questionnaire improved for the domains general health, role limitations, emotions, physical limitations, personal limitations and incontinence impact significantly. Micturition pressure dropped significantly from 43cmH2O (95% CI 19-59cmH2O) to 18cmH2O (95% CI 16-23.5 H2O). Residual urine changed from 110ml (range 20-380ml) to 32ml (20-115ml). Bladder wall thickness decreased from 7mm (95% CI 6.235-7.152) to 5mm (95% CI 5.037-5.607; p<0.01). CONCLUSION Urethrolysis may resolve patients' symptoms and lower micturition pressure but irritative symptoms may persist.

Turgor Regulation via Cell Wall Adjustment in White Spruce1

Turgor regulation at reduced water contents was closely associated with changes in the elastic quality of the cell walls of individual needles and shoots of naturally drought-resistant seedlings of white spruce (Picea glauca [Moench] Voss.) and of seedlings of intermediate resistance that had been pretreated with paclobutrazol, a stress-protecting, synthetic plant-growth regulator. Paclobutrazol-treated seedlings showed marked increases in drought resistance, and pressure-volume analysis combined with Chardakov measurements confirmed observations that water stress was ameliorated during prolonged drought. Turgor was maintained in the paclobutrazol-treated and in the naturally resistant drought-stressed seedlings despite water contents near or below the turgor-loss volumes of well-watered controls. The maintenance of turgor in these seedlings was in large part a function of the dynamic process of cell wall adjustment, as reflected by marked reductions in both the saturated and turgor-loss volumes and by large increases in the elastic coefficients of the tissues. Shear and Young's moduli, calculated from pressure-volume curves and the radii and wall thicknesses of mesophyll cells, also confirmed observed changes in the elastic qualities of the cell walls. Elastic coefficients of well-watered, paclobutrazol-treated seedlings were consistently larger than those in well-watered controls and several times larger than the values in untreated plants, which succumbed rapidly to drought. In contrast, untreated seedlings that withstood prolonged drought without wilting displayed elastic coefficients similar to those in seedlings that had been treated with paclobutrazol but that had not been exposed to drought.

The Role of Iron-Deficiency Stress Responses in Stimulating Heavy-Metal Transport in Plants1

Plant accumulation of Fe and other metals can be enhanced under Fe deficiency. We investigated the influence of Fe status on heavy-metal and divalent-cation uptake in roots of pea (Pisum sativum L. cv Sparkle) seedlings using Cd2+ uptake as a model system. Radiotracer techniques were used to quantify unidirectional 109Cd influx into roots of Fe-deficient and Fe-sufficient pea seedlings. The concentration-dependent kinetics for 109Cd influx were graphically complex and nonsaturating but could be resolved into a linear component and a saturable component exhibiting Michaelis-Menten kinetics. We demonstrated that the linear component was apoplastically bound Cd2+ remaining in the root cell wall after desorption, whereas the saturable component was transporter-mediated Cd2+ influx across the root-cell plasma membrane. The Cd2+ transport system in roots of both Fe-deficient and Fe-sufficient seedlings exhibited similar Michaelis constant values, 1.5 and 0.6 μm, respectively, for saturable Cd2+ influx, whereas the maximum initial velocity for Cd2+ uptake in Fe-deficient seedlings was nearly 7-fold higher than that in Fe-grown seedlings. Investigations into the mechanistic basis for this response demonstrated that Fe-deficiency-induced stimulation of the plasma membrane H+-ATPase did not play a role in the enhanced Cd2+ uptake. Expression studies with the Fe2+ transporter cloned from Arabidopsis, IRT1, indicated that Fe deficiency induced the expression of this transporter, which might facilitate the transport of heavy-metal divalent cations such as Cd2+ and Zn2+, in addition to Fe2+.

Oxidative Burst and Hypoosmotic Stress in Tobacco Cell Suspensions

Oxidative burst constitutes an early response in plant defense reactions toward pathogens, but active oxygen production may also be induced by other stimuli. The oxidative response of suspension-cultured tobacco (Nicotiana tabacum cv Xanthi) cells to hypoosmotic and mechanical stresses was characterized. The oxidase involved in the hypoosmotic stress response showed similarities by its NADPH dependence and its inhibition by iodonium diphenyl with the neutrophil NADPH oxidase. Activation of the oxidative response by hypoosmotic stress needed protein phosphorylation and anion effluxes, as well as opening of Ca2+ channels. Inhibition of the oxidative response impaired Cl− efflux, K+ efflux, and extracellular alkalinization, suggesting that the oxidative burst may play a role in ionic flux regulation. Active oxygen species also induced the cross-linking of a cell wall protein, homologous to a soybean (Glycine max L.) extensin, that may act as part of cell volume and turgor regulation through modification of the physical properties of the cell wall.

Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress.

Early atherosclerotic lesions develop in a topographical pattern that strongly suggests involvement of hemodynamic forces in their pathogenesis. We hypothesized that certain endothelial genes, which exhibit differential responsiveness to distinct fluid mechanical stimuli, may participate in the atherogenic process by modulating, on a local level within the arterial wall, the effects of systemic risk factors. A differential display strategy using cultured human endothelial cells has identified two genes, manganese superoxide dismutase and cyclooxygenase-2, that exhibit selective and sustained up-regulation by steady laminar shear stress (LSS). Turbulent shear stress, a nonlaminar fluid mechanical stimulus, does not induce these genes. The endothelial form of nitric oxide synthase also demonstrates a similar LSS-selective pattern of induction. Thus, three genes with potential atheroprotective (antioxidant, antithrombotic, and antiadhesive) activities manifest a differential response to distinct fluid mechanical stimuli, providing a possible mechanistic link between endothelial gene expression and early events in atherogenesis. The activities of these and other LSS-responsive genes may have important implications for the pathogenesis and prevention of atherosclerosis.

Coral communities exposed to differential large amplitude internal waves cooling and a severe heat stress in 2010 in the Andaman Sea

Tropical scleractinian corals are particularly vulnerable to global warming as elevated sea surface temperatures (SST) disrupt the delicate balance between the coral host and their algal endosymbionts, leading to symbiont expulsion, mass bleaching and mortality. While satellite sensing of SST has proven a good predictor of coral bleaching at the regional scale, there are large deviations in bleaching severity and mortality on the local scale, which are only poorly understood. Here, we show that internal waves play a major role in explaining local coral bleaching and mortality patterns in the Andaman Sea. In spite of a severe region-wide SST anomaly in May 2010, frequent upslope intrusions of cold sub-pycnocline waters due to breaking large amplitude internal waves (LAIW) alleviated heating and mitigated coral bleaching and mortality in shallow LAIW-exposed waters. In LAIW-sheltered waters, by contrast, bleaching susceptible species suffered severe bleaching and total mortality. These findings suggest that LAIW, which are ubiquitous in tropical stratified waters, benefit coral reefs during thermal stress and provide local refugia for bleaching susceptible corals. The swash zones of LAIW may thus be important, so far overlooked, conservation areas for the maintainance of coral diversity in a warming climate. The consideration of LAIW can significantly improve coral bleaching predictions and can provide a valuable tool for coral reef conservation and management.

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.