Redox stress defines the small artery vasculopathy of hypertension: how do we bridge the bench-to-bedside gap?

Although convincing experimental evidence demonstrates the importance of vascular reactive oxygen and nitrogen species (RONS), oxidative stress, and perturbed redox signaling as causative processes in the vasculopathy of hypertension, this has not translated to the clinic. We discuss this bench-to-bedside disparity and the urgency to progress vascular redox pathobiology from experimental models to patients by studying disease-relevant human tissues. It is only through such approaches that the unambiguous role of vascular redox stress will be defined so that mechanism-based therapies in a personalized and precise manner can be developed to prevent, slow, or reverse progression of small-vessel disorders and consequent hypertension

Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics/Fluid-Structure Interaction Pilot Study to Detect Early Vascular Changes in Pediatric Patients with Type 1 Diabetes

We hypothesized that pediatric patients with type 1 diabetes have cardiac magnetic resonance (CMR) detectable differences in thoracic aortic wall properties and hemodynamics leading to significant local differences in indices of wall shear stress, when compared with age-matched control subjects without diabetes. Pediatric patients with type 1 diabetes were recruited from Children’s Hospital of Wisconsin and compared with controls. All underwent morning CMR scanning, 4-limb blood pressure, brachial artery reactivity testing, and venipuncture. Patient-specific computational fluid dynamics modeling with fluid–structure interaction, based on CMR data, determined regional time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 diabetic subjects, median age 15.8 years (11.6–18.4) and 8 controls 15.4 years (10.3–18.2) were similar except for higher glucose, hemoglobin A1c, and triglycerides for type 1 diabetic subjects. Lower flow-mediated dilation was seen for those with type 1 diabetes (6.5) versus controls (7.8), p = 0.036. For type 1 diabetic subjects, the aorta had more regions with high TAWSS when compared to controls. OSI maps appeared similar. Flow-mediated dilation positively correlated with age at diabetes diagnosis (r = 0.468, p = 0.038) and hemoglobin A1c (r = 0.472, p = 0.036), but did not correlate with aortic distensibility, TAWSS, or OSI. TAWSS did not correlate with any clinical parameter for either group. CMR shows regional differences in aortic wall properties for young diabetic patients. Some local differences in wall shear stress indices were also observed, but a longitudinal study is now warranted

A dynamical framework for the origin of the diagonal South Pacific and South Atlantic convergence zones

The South Pacific Convergence Zone (SPCZ) and South Atlantic Convergence Zone (SACZ) are diagonal bands of precipitation that extend from the equator southeastward into the Southern Hemisphere over the western Pacific and Atlantic Oceans, respectively. With mean precipitation rates over 5 mm day−1, they are a major component of the tropical and global climate in austral summer. However, their basic formation mechanism is not fully understood. Here, a conceptual framework for the diagonal convergence zones is developed, based on calculations of the vorticity budget from reanalysis and Rossby wave theory. Wave trains propagate eastward along the Southern Hemisphere subtropical jet, with initially quasi-circular vorticity centres. In the zonally sheared environment on the equatorward flank of the jet, these vorticity centres become elongated and develop a northwest-southeast tilt. Ray tracing diagnostics in a non-divergent, barotropic Rossby wave framework then explain the observed equatorward propagation of these diagonal vorticity structures toward the westerly ducts over the equatorial Pacific and Atlantic. The baroclinic component of these circulations leads to destabilisation and ascent ahead of the cyclonic vorticity anomaly in the wave, triggering deep convection because of the high sea surface temperatures in this region. Latent heat release then forces additional ascent and strong upper-tropospheric divergence, with an associated anticyclonic vorticity tendency. A vorticity budget shows that this cancels out the advective cyclonic vorticity tendency in the wave train over the SPCZ, and dissipates the wave within a day. The mean SPCZ is consequently comprised of the sum of these pulses of diagonal bands of precipitation. Similar mechanisms also operate in the SACZ. However, the vorticity anomalies in the wave trains are stronger, and the precipitation and negative feedback from the divergence and anticyclonic vorticity tendency are weaker, resulting in continued propagation of the wave and a more diffuse diagonal convergence zone

Why the South Pacific Convergence Zone is diagonal

During austral summer, the majority of precipitation over the Pacific Ocean is concentrated in the South Pacific Convergence Zone (SPCZ). The surface boundary conditions required to support the diagonally (northwest-southeast) oriented SPCZ are determined through a series of experiments with an atmospheric general circulation model. Continental configuration and orography do not have a significant influence on SPCZ orientation and strength. The key necessary boundary condition is the zonally asymmetric component of the sea surface temperature (SST) distribution. This leads to a strong subtropical anticyclone over the southeast Pacific that, on its western flank, transports warm moist air from the equator into the SPCZ region. This moisture then intensifies (diagonal) bands of convection that are initiated by regions of ascent and reduced static stability ahead of the cyclonic vorticity in Rossby waves that are refracted toward the westerly duct over the equatorial Pacific. The climatological SPCZ is comprised of the superposition of these diagonal bands of convection. When the zonally asymmetric SST component is reduced or removed, the subtropical anticyclone and its associated moisture source is weakened. Despite the presence of Rossby waves, significant moist convection is no longer triggered; the SPCZ disappears. The diagonal SPCZ is robust to large changes (up to +/-6 degC) in absolute SST (i.e. where the SST asymmetry is preserved). Extreme cooling (change less than -6 degC) results in a weaker and more zonal SPCZ, due to decreasing atmospheric temperature, moisture content and convective available potential energy

The Southwest Pacific Ocean circulation and climate experiment (SPICE) : report to CLIVAR SSG

The Southwest Pacific Ocean Circulation and Climate Experiment (SPICE) is an international research program under the auspices of CLIVAR. The key objectives are to understand the Southwest Pacific Ocean circulation and the South Pacific Convergence Zone (SPCZ) dynamics, as well as their influence on regional and basin-scale climate patterns. South Pacific thermocline waters are transported in the westward flowing South Equatorial Current (SEC) toward Australia and Papua-New Guinea. On its way, the SEC encounters the numerous islands and straits of the Southwest Pacific and forms boundary currents and jets that eventually redistribute water to the equator and high latitudes. The transit in the Coral, Solomon, and Tasman Seas is of great importance to the climate system because changes in either the temperature or the amount of water arriving at the equator have the capability to modulate the El Nino-Southern Oscillation, while the southward transports influence the climate and biodiversity in the Tasman Sea. After 7 years of substantial in situ oceanic observational and modeling efforts, our understanding of the region has much improved. We have a refined description of the SPCZ behavior, boundary currents, pathways, and water mass transformation, including the previously undocumented Solomon Sea. The transports are large and vary substantially in a counter-intuitive way, with asymmetries and gating effects that depend on time scales. This paper provides a review of recent advancements and discusses our current knowledge gaps and important emerging research directions

Tea Consumption Enhances Endothelial-Dependent Vasodilation; a Meta-Analysis

Background: Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association. Objective: We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk. Methods: Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical Abstracts and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity. Results: In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6 % of the arterial diameter (95 % CI: 1.8-3.3%; P-value,0.001) for a median daily dose of 500 mL of tea (2–3 cups). This is a relative increase of approximately 40 % compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value,0.001) tha

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background. Flow-mediated dilation (FMD) and carotid intima-medial thickness (CIMT), measured by ultrasound, are widely used to test the efficacy of cardioprotective interventions. Although assessment methods vary, automated edge-detecting image analysis software is routinely used to measure changes in FMD and CIMT. We aimed to quantify the effect that commonly adjusted ultrasound settings have on arterial lumen and wall thickness measurements made with CIMT measurement software. Methods. We constructed phantom arteries from a tissue-mimicking agar compound and scanned them in a water bath with a 10 MHz multi-frequency linear-array probe attached to a high-resolution ultrasound machine. B-mode images of the phantoms were recorded with dynamic range (DR) and gain set at five decibel (dB) increments from 40 dB to 60 dB and -10 dB to +10 dB respectively. Lumen diameter and wall-thickness were measured off-line using CIMT measurement software. Results. Lumen measurements: there was a strong linear relationship between DR and gain and measured lumen diameter. For a given gain level, a 5 dB increase in DR reduced the measured lumen diameter by 0.02 ± 0.004 mm (p \u3c 0.001). For a given DR level, a 5 dB increase in gain reduced measured lumen diameter by 0.04 ± 0.004 mm (p \u3c 0.001). A 5 mm increase in distance between the ultrasound probe and the artery reduced measured lumen diameter by 0.04 ± 0.03 mm (p \u3c 0.001). CIMT measurements: For a fixed gain level, a 5 dB increase in DR increased measured wall thickness by 0.003 ± 0.002 mm (p \u3c 0.001). The effects of increasing gain were not consistent and appeared to vary depending on the distance between the artery and the ultrasound probe and the thickness of the artery wall. Conclusion. DR, gain and probe distance significantly alter lumen diameter and CIMT measurements made using image analysis software. When CIMT and FMD are used to test the efficacy of cardioprotective interventions, the DR, gain and probe position used to record baseline scans should be documented and replicated in post-treatment scans in individual trial subjects. If more than one sonographer or imaging centre is used to collect data, the study protocol should document specific DR and gain settings to be used in all subjects

The effects of tea extracts on proinflammatory signaling

BACKGROUND: Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea. METHODS: Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNFα and PGE(2 )release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays. RESULTS: Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation CONCLUSION: Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate