Increase In Vessel Diameter Research Articles

Effect of Elevated CO2 and Drought on Biomass, Gas Exchange and Wood Structure of Eucalyptus grandis

Juvenile Eucalyptus grandis were exposed to drought and elevated CO2 to evaluate the independent and interactive effects on growth, gas exchange and wood structure. Trees were grown in a greenhouse at ambient and elevated CO2 (aCO2, 410 ppm; eCO2, 950 ppm), in combination with daily irrigation and cyclic drought during one growing season. The results demonstrated that drought stress limited intercellular CO2 concentration, photosynthesis, stomatal conductance, and transpiration, which correlated with a lower increment in height, stem diameter and biomass. Drought also induced formation of frequent and narrow vessels accompanied by a reduction in vessel lumen area. Conversely, elevated CO2 increased intercellular CO2 concentration as well as photosynthesis, and partially closed stomata, leading to a more efficient water use, especially under drought. There was a clear trend towards greater biomass accumulation at eCO2, although the results did not show statistical significance for this parameter. We observed an increase in vessel diameter and vessel lumen area at eCO2, and, contrarily, the vessel frequency decreased. Thus, we conclude that eCO2 delayed the effects of drought and potentialized growth. However, results on vessel anatomy suggest that increasing vulnerability to cavitation due to formation of larger vessels may counteract the beneficial effects of eCO2 under severe drought.

The Endothelial Glycocalyx and Retinal Hemodynamics.

Previous studies suggest that the endothelial glycocalyx adds to vascular resistance, inhibits thrombosis, and is critical for regulating homogeneous blood flow and ensuring uniform red blood cell (RBC) distribution. However, these functions and consequences of the glycocalyx have not been examined in the retina. We hypothesize that the endothelial glycocalyx is a critical regulator of retinal hemodynamics and perfusion and decreases the propensity for retinal thrombus formation. Hyaluronidase and heparinase, which are endothelial glycocalyx-degrading enzymes, were infused into mice. Fluorescein isothiocyanate-dextran (2000 kDa) was injected to measure lumen diameter, while RBC velocity and distribution were measured using fluorescently labeled RBCs. The diameters and velocities were used to calculate retinal blood flow and shear rates. Mean circulation time was calculated by measuring the difference between arteriolar and venular mean transit times. Rose Bengal dye was infused, followed by illumination with a green light to induce thrombosis. The acute infusion of hyaluronidase and heparinase led to significant increases in both arteriolar (7%) and venular (16%) diameters in the retina, with a tendency towards increased arteriolar velocity. In addition, the degradation caused a significant decrease in the venular shear rate (14%). The enzyme infusion resulted in substantial increases in total retinal blood flow (26%) and retinal microhematocrit but no changes in the mean circulation time through the retina. We also observed an enhanced propensity for retinal thrombus formation with the removal of the glycocalyx. Our data suggest that acute degradation of the glycocalyx can cause significant changes in retinal hemodynamics, with increases in vessel diameter, blood flow, microhematocrit, pro-thrombotic conditions, and decreases in venular shear rate.

Three‐dimensional study on morphological changes of arterioles in Cerebral Amyloid Angiopathy

AbstractBackgroundThe accumulation of β‐amyloid plaques in the brain is a hallmark of Alzheimer’s disease. Vascular involvement is also common in the form of cerebral amyloid angiopathy (CAA), a vasculopathy that is produced when the β‐amyloid forms toxic deposits on vessels wall. The accumulation of β‐amyloid makes blood vessels stiff and increases the thickness of the vessel wall, reducing the blood flow and energy supply for the tissue. This predisposes to hemorrhage and contribute to cognitive decline and stroke.MethodWe used the CLARITY method to analyze tissue samples from patients with CAA to characterize changes to vessel morphology associated with vascular degeneration. The blood vessels were stained with isolectin, β‐amyloid with thiazine red, and proteins with primary antibodies associated with the vascular structure. We conducted 3D microscopy using a light sheet microscope and performed surface volume reconstruction to assess the morphology of rupturing vessel. We also measured arteriolar stiffness of vessels damaged using atomic force microscopy (AFM). Finally, we assessed cerebral blood flow and autoregulation in vivo in a novel mouse model of CAA using laser speckle flowetry.ResultVessels with CAA demonstrate an organized ring‐shaped deposits β‐amyloid. At sites, these rings are shattered and the vessel diameter increase. Degenerating vessels also demonstrate depletion of vascular smooth muscle, circumferential luminal dilation, and thickening of the vessel wall. Lysyl oxidase levels and markers of fibrosis are increased in vessels with degenerating features. We found that the arteriolar wall was more than 400% stiffer in CAA than in arterioles without CAA in the mice model. Finally, in a novel mouse model of CAA we are terming the VASC‐FAD model, resting cerebral blood flow and vasoreactivity are both reduced.ConclusionCombining the CLARITY technique associated with surface volume rendering and AFM we have a better overview of microhemorrhages to understand the vascular fragility and morphological changes, and accumulation of myofibroblast markers caused by the β‐amyloid deposition and stiffness. These features combine to alter the physiology of cerebral blood flow. Defining mechanism of microvascular degeneration in AD and CAA may lead to novel treatment targets to restore the ECM and vascular network integrity.

Direct current stimulation increases blood flow and permeability of cortical microvasculature in vivo.

Transcranial direct current stimulation (DCS) structurally and functionally modulates neuronal networks and microglia dynamics. Neurovascular coupling adapts regional cerebral blood flow to neuronal activity and metabolic demands. In this study, we examined effects of anodal DCS on vessel morphology, blood flow parameters, permeability of cortical microvasculature, and perivascular microglia motility by time-lapse two-photon microscopy in anaesthetized mice. Low-intensity DCS significantly increased vessel diameter and blood flow parameters. These effects were transient and dependent on the spontaneous vasomotion characteristics of the individual vessel. Vessel leakage increased significantly after DCS at 1.1 and was more pronounced at 2.2A/m2 , indicating a dose-dependent increase in vascular permeability. Perivascular microglia exhibited increased soma motility post-DCS at both intensities, potentially triggered by the extravasation of intravascular substrates. Our findings demonstrate that DCS affected only vessels with spontaneous vasomotion. This rapid vascular response may occur as an adaptation of regional blood supply to neuronal excitability altered by DCS or as a direct effect on the vessel wall. In contrast to these immediate effects during stimulation, increases in cortical vessel permeability and perivascular microglia motility appeared after the stimulation had ended.

Intravital Microscopy of the Native Thymus

Hematopoietic Cell Transplantation (HCT) is a common treatment for patients suffering from a variety of malignant or benign diseases, reconstituting the hematopoietic system after preconditioning treatment. In patients undergoing HCT, the capacity for the thymus to produce functional T cells is inhibited due to damage from the cytotoxic preconditioning. Endogenous thymus regeneration depends on the complex relationship between thymus stromal cells (including vascular endothelial cells (EC)) and the recruitment of de novo "seeding" thymic progenitor cells (TPCs) from the regenerated bone marrow (BM). It has been demonstrated that ECs are radio-resistant, however in the context of HCT, it is not clear which type of EC (arterial, venous, or capillary) can survive following injury. Moreover, ECs are critical cells in endogenous thymic regeneration and are involved in recruiting TPCs from the BM, but functional damage to the vascular network may alter the hemodynamics and negatively impact TPC homing and thymus regeneration. Flow cytometry, immunohistochemistry, and ex vivo imaging techniques have been applied to study the thymus in preclinical mouse models since direct visualization of the native thymus in live mice was deemed impossible. Teleost fish are an alternative model organism for direct thymus observation in vivo but redundant cytokine pathways are present which do not exist in humans and mice. Unlike fish models, in mammals T cell development critically depends on the IL-7 cytokine signaling pathway. Therefore, tools to directly visualize the mouse thymus are needed in order to study functional changes to the vascular system after cytotoxic preconditioning in an immunologically relevant preclinical animal model. We hypothesize that cytotoxic preconditioning causes functional and anatomical changes in blood vessel architecture, especially cortical vasculature, that negatively impacts TPC homing and leads to long-term changes in the thymus microenvironment. In this project, we developed intravital imaging techniques to visualize the native thymus in live mice. Using our methodology, we were able to quantify the changes to the blood vessel network after sublethal irradiation (4.5 Gy). Our results showed an increase in blood vessel diameter in mice one day after receiving irradiation. We validated this result using tissue clearing and ex vivo imaging. In addition, most cortical blood flow velocity is <500 µm/s in both control and one day after sublethal irradiation, although no significant changes were observed in blood flow velocity and shear rate between the groups at this timepoint. Taken together, our study suggests that native intravital thymus imaging is a powerful technique enabling functional and anatomical characterization of the thymus vascular network. We believe, further work will help clarify the changes to the vascular system at later timepoints and in the context of higher irradiation doses. This method enables a whole new paradigm for studying thymus biology not previously possible.

Diosmin and its glycocalyx restorative and anti-inflammatory effects on injured blood vessels.

The endothelium, a crucial homeostatic organ, regulates vascular permeability and tone. Under physiological conditions, endothelial stimulation induces vasodilator endothelial nitric oxide (eNO) release and prevents adhesion molecule accessibility and leukocyte adhesion and migration into vessel walls. Endothelium dysfunction is a principal event in cardiovascular disorders, including atherosclerosis. Minimal attention is given to an important endothelial cell structure, the endothelial glycocalyx (GCX), a negatively charged heterogeneous polysaccharide that serves as a protective covering for endothelial cells and enables endothelial cells to transduce mechanical stimuli into various biological and chemical activities. Endothelial GCX shedding thus plays a role in endothelial dysfunction, for example by increasing vascular permeability and decreasing vessel tone. Consequently, there is increasing interest in developing therapies that focus on GCX repair to limit downstream endothelium dysfunction and prevent further downstream cardiovascular events. Here, we present diosmin (3',5,7-trihydroxy-4'-methoxyflavone-7-rhamnoglucoside), a flavone glycoside of diosmetin, which downregulates adhesive molecule expression, decreases inflammation and capillary permeability, and upregulates eNO expression. Due to these pleiotropic effects of diosmin on the vasculature, a possible unidentified mechanism of action is through GCX restoration. We hypothesize that diosmin positively affects GCX integrity along with GCX-related endothelial functions. Our hypothesis was tested in a partial ligation left carotid artery (LCA) mouse model, where the right carotid artery was the control for each mouse. Diosmin (50 mg/kg) was administered daily for 7 days, 72h after ligation. Within the ligated mice LCAs, diosmin treatment elevated the activated eNO synthase level, inhibited inflammatory cell uptake, decreased vessel wall thickness, increased vessel diameter, and increased GCX coverage of the vessel wall. ELISA showed a decrease in hyaluronan concentration in plasma samples of diosmin-treated mice, signifying reduced GCX shedding. In summary, diosmin supported endothelial GCX integrity, to which we attribute diosmin's preservation of endothelial function as indicated by attenuated expression of inflammatory factors and restored vascular tone.

Balloon angioplasty and stent implantation within 30 days postcongenital heart surgery (CHS) in children.

This study aims to assess balloon angioplasty (BAP) and stent implantation (SI) procedures early after congenital heart surgery (CHS) in children. These interventions are considered potential high-risk procedures and often avoided or postponed. This is a retrospective, single centre study of all BAP and SI procedures within 30 days after CHS (01/2001 until 01/2021). A total of 127 (96 SI, 31 BAP) procedures were performed in 104 patients at median 6.5 days (interquartile range: 1-15) after CHS. Balloon-to-stenosis ratio and balloon-to-reference vessel ratio were significantly smaller compared to stent-to-stenosis ratio and stent-to-reference vessel ratio (p < .001 and p = .005). There was a greater rise in absolute vessel diameter, greater rise in vessel diameter in relation to the stenosis and vessel diameter in relation to the reference vessel with SI (p < .001, p = .01, and p < .001). Up to 94% SIs fulfilled both success criteria (increase of vessel diameter ≥50% of minimal vessel diameter or achievement ≥75% of the reference vessel diameter). Major adverse events were more frequent in the BAP group (p = .05). Intraprocedural complications were 5/31 (16%) in the BAP group and 13/96 (13%) in the SI group (p = .77). BAP and SI procedures within 30 days post-CHS can be performed safely, with a greater stent-to-stenosis ratio and a greater rise in vessel diameter with stent implantation.

Preserved Endothelium-independent Function With Aging: Evidence From The Peripheral And Cerebral Vasculature

There is growing evidence that vascular endothelial dysfunction is not only antecedent to cardiovascular disease, but also cognitive dysfunction and Alzheimer’s disease. Vascular smooth muscle cells (VSMCs) translate the endothelial-derived signal to vasodilate into action. PURPOSE: However, in the peripheral, and especially the cerebral, vasculature, the impact of aging on the functional capacity of VSMCs, and any functional link between these vascular beds, is not well understood. METHODS: Therefore, endothelium-independent dilation, elicited by sublingual nitroglycerin (NTG, 2 tabs, 0.4 mg Nitrostat each), compared to sham-delivery (control), was assessed using Doppler ultrasound in both the popliteal and middle cerebral (MCA) arteries of 12 young (22 ± 4 yrs, 6 male/6 female) and 11 old (67 ± 3 yrs, 6 male/5 female) healthy adults. RESULTS: In the popliteal artery, when compared to control (∆ young: 0.00 ± 0.03 mm, ∆ old: 0.02 ± 0.05 mm), NTG resulted in significant increases in vessel diameter (∆ young: 0.32 ± 0.13 mm, ∆ old: 0.37 ± 0.13 mm) with no differences between age or sex. Similarly, in the MCA, when compared to control (∆ young: 0.07 ± 0.11 mm, ∆ old: 0.02 ± 0.20 mm), NTG resulted in significant increases in vessel diameter (∆ young: 1.01 ± 0.30 mm, ∆ old: 1.00 ± 0.38 mm) with no differences between age or sex. Interestingly, there was no evidence of a relationship between the peripheral and cerebral vascular responses to NTG in terms of either age, sex, or all subjects as a whole. CONCLUSION: Thus, the known age-related vascular dysfunction, in the peripheral and cerebral circulations, does not appear to be the consequence of dysfunctional VSMCs, and there is no evidence of a link between VSMC function in these two vascular beds.

Functional trade-offs in volume allocation to xylem cell types in 75 species from the Brazilian savanna Cerrado.

Xylem is a crucial tissue for plant survival, performing the functions of water transport, mechanical support and storage. Functional trade-offs are a result of the different assemblages of xylem cell types within a certain wood volume. We assessed how the volume allocated to different xylem cell types can be associated with wood functional trade-offs (hydraulics, mechanical and storage) in species from the Cerrado, the Brazilian savanna. We also assessed the xylem anatomical characters linked to wood density across species. We analysed cross-sections of branches collected from 75 woody species belonging to 42 angiosperm families from the Cerrado. We estimated the wood volume fraction allocated to different cell types and performed measurements of vessel diameter and wood density. The largest volume of wood is allocated to fibres (0.47), followed by parenchyma (0.33) and vessels (0.20). Wood density is positively correlated to cell wall (fibre and vessel wall), and negatively to the fractions of fibre lumen and gelatinous fibres. We observed a trade-off between hydraulics (vessel diameter) and mechanics (cell wall fraction), and between mechanics and storage (parenchyma fraction). The expected positive functional relationships between hydraulics (vessel diameter) and water and carbohydrate storage (parenchyma and fibre lumen fractions) were not detected, though larger vessels are linked to a larger wood volume allocated to gelatinous fibres. Woody species from the Cerrado show evidence of functional trade-offs between water transport, mechanical support and storage. Gelatinous fibres might be potentially linked to water storage and release by their positive relationship to increased vessel diameter, thus replacing the functional role of parenchyma and fibre lumen cells. Species can profit from the increased mechanical strength under tension provided by the presence of gelatinous fibres, avoiding expensive investments in high wood density.

Alterungsbedingte Gefäßveränderungen am Beispiel der Arteria carotis

Einer der Hauptrisikofaktoren für das Vorliegen einer Karotisstenose und des karotisbedingten Schlaganfalls ist das Lebensalter. Ziel dieses Übersichtsartikels ist die Darstellung des aktuellen Wissensstands über altersbedingte Veränderungen der Gefäße am Beispiel der Karotisstenose.Die Gefäßalterung (vaskuläre Seneszenz) als Abnahme struktureller und funktioneller Eigenschaften der Gefäßwand spielt sich auf verschiedenen Ebenen ab. Auf multizellulärer Ebene kommt es mit zunehmendem Alter hauptsächlich aufgrund von atherosklerotischen Veränderungen der Gefäßwand zu einer Zunahme von Gefäßvolumen und -durchmesser sowie der Intima-Media-Dicke. Auf zellulärer und extrazellulärer Ebene kommt es zur Abnahme von Elastinfasern, glatten Muskelzellen und der Gesamtzellularität sowie zur Zunahme der Lipid‑, Cholesterin- und Kalziumphosphatablagerungen und der Neovaskularisierung. Ursachen der Gefäßalterung auf molekularer Ebene sind insbesondere oxidativer Stress, chronische Entzündungsreaktion, mitochondriale Dysfunktion, epigenetische Veränderungen, Dysregulation der Expression nicht kodierender RNAs (ncRNAs) und die Zunahme der Seneszenz. Der altersbedingte Verlust der Heilungs- und Reparaturfähigkeit des Gewebes macht die Plaques vulnerabler und im Falle der A. carotis anfälliger für ischämische Schlaganfälle.Zunehmende Erkenntnisse über den Einfluss des Alterns auf die Epigenetik und der ncRNAs in atherosklerotischen Plaques kann zukünftig das individuelle Risiko von Patienten genauer quantifizieren und zur Entwicklung zielgerichteter Therapiestrategien beitragen. Weitere Studien sind auf diesem Gebiet jedoch notwendig, um das gesamte Ausmaß der Gefäßalterung und den damit einhergehenden Erkrankungen zu verstehen, damit diesen dann gezielt entgegenwirkt werden kann.

Mathematical Modeling of Vessel Geometry and Circumference in Microvascular Surgery.

Microvascular anastomosis has traditionally been executed with a perpendicular transection through the vessel at the widest diameter to increase circumference and thus increase blood flow while decreasing resistance. In Chen's 2015 article, it was suggested that an "open Y" would improve vessel size match, and Wei and Mardini discuss angled transections of the vessels. This project aims to explore the geometric configurations feasible at the anastomotic transection and mathematically model the resulting hypothetical increases in circumference. The mathematical models were theoretically developed by our team. The formulas model increases in circumference of the transection at different distances in relation to the bifurcation of a blood vessel, as well as changes in circumference at different transection angulations. An in vitro exploration as to the anastomotic feasibility of each geometric cut was completed on ten poultry tissue specimens. The mathematical models demonstrated the change in vessel circumference, with multiple geometric designs calculated, best shown through diagrams. For example, if the vessel width is 1mm, the distance from the increasing vessel diameter to the final bifurcation is 1mm, and the bifurcation angle is 45°, the circumference of the transected vessel increases by 82.8%. Models of transections at different angulations, for instance 30°, 45°, and 60°, yield an increase in elliptical circumference of 8.0%, 22.5%, and 58.1%, respectively. Additional derivations calculate the elliptical circumference at any angle in a single vessel, and at any angle in a bifurcating vessel. The theoretical and clinical aim of this project is to increase awareness of the anastomotic creativity and mathematically demonstrate the optimal anastomotic geometry, which has not been objectively explored to our knowledge. An in vivo study would further support clinical improvements, with the aim to map postoperative fluid dynamics through the geometric anastomoses.

PATENCY RATE OF BRACHIOCEPHALIC VS RADIOCEPHALIC AVF IN CHRONIC KIDNEY DISEASE PATIENTS IN POPULATION OF D.I.KHAN DIVISION, PAKISTAN

Background: All patients with chronic renal failure need vascular access for hemodialysis that is possible with CVP line but it can be retained for only 02-03weeks due to infection. The most suitable and effective vascular access on long term basis is the creation of arteriovenous fistula (AVF). The objective of this study was to compare the patency rate of Radiocephalic vs Brachiocephalic AVFs in population of D.I.Khan division, Pakistan. Materials &amp; Methods: This randomized controlled trail was conducted in the surgical unit at District Headquarter Teaching Hospital D.I.Khan, Pakistan from January 2017 to January 2020. Two hundred and sixty six patients were randomly allocated by toss method into two groups, one for Brachiocephalic AVF (BCAVF) and second for Radiocephalic AVF (RCAVF). Sex &amp; patency rates were our nominal while age grouping was our ordinal variable. The data for the sample was described by count &amp; percentages &amp; was analyzed for the population as confidence interval at 80% confidence level. McNemar chi-square test was used to test hypothesis to compare the patency rate of Brachiocephalic AVF vs. Radiocephalic AVF at alpha 0.05 with Yates continuity correction using online statistical calculator. Results: The patency was present in 129 (97%, 80% CI 94.45-98.39%) cases &amp; absent in 4 (3%, 80% CI 1.61-5.55%) cases in Brachiocephalic AVF group while it was present in 107 (80.5%, 80% CI 76.04-84.86%) cases &amp; absent in 26 (19.5%, 80% CI 15.52-24.32%) cases in Radiocephalic AVF group. McNemar chi-square test showed p-value of &lt;.0001 (less than alpha). So, the null hypothesis was rejected, showing significant difference between two groups. Conclusion: Brachiocephalic AVF creation is more ideal in terms of patency and maturation as compare to Radiocephalic AVF because of increased vessel diameter and increased arterial pressure at proximal site below elbow joint.

Comparative anatomy of leaf petioles in temperate trees and shrubs: the role of plant size, environment and phylogeny.

Petioles are important plant organs connecting stems with leaf blades and affecting light-harvesting ability of the leaf as well as transport of water, nutrients and biochemical signals. Despite the high diversity in petiole size, shape and anatomy, little information is available regarding their structural adaptations across evolutionary lineages and environmental conditions. To fill this knowledge gap, we investigated the variation of petiole morphology and anatomy of mainly European woody species to better understand the drivers of internal and external constraints in an evolutionary context. We studied how petiole anatomical features differed according to whole-plant size, leaf traits, thermal and hydrological conditions, and taxonomic origin in 95 shrubs and trees using phylogenetic distance-based generalized least squares models. Two major axes of variation were related to leaf area and plant size. Larger and softer leaves are found in taller trees of more productive habitats. Their petioles are longer, with a circular outline and are anatomically characterized by the predominance of sclerenchyma, larger vessels, interfascicular areas with fibres and indistinct phloem rays. In contrast, smaller and tougher leaves are found in shorter trees and shrubs of colder or drier habitats. Their petioles have a terete outline, phloem composed of small cells and radially arranged vessels, fibreless xylem and lamellar collenchyma. Individual anatomical traits were linked to different internal and external drivers. Petiole length and vessel diameter increase with increasing leaf blade area. Collenchyma becomes absent with increasing temperature, and petiole outline becomes polygonal with increasing precipitation. We conclude that species' temperature and precipitation optima, plant height, and leaf area and thickness exerted a significant control on petiole anatomical and morphological structures not confounded by phylogenetic inertia. Species with different evolutionary histories but similar thermal and hydrological requirements have converged to similar petiole anatomical structures.

Effect of hyperoxia and hypoxia on retinal vascular parameters assessed with optical coherence tomography angiography.

To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT-A) and retinal vessel analyzer. Twenty-four healthy volunteers participated in this randomized, double-masked, cross-over study. For each subject, two study days were scheduled: on one study day, hyperoxia was induced by breathing 100% oxygen whereas on the other study day, hypoxia was induced by breathing a mixture of 88% nitrogen and 12% oxygen. Perfusion density was calculated in the superficial vascular plexus (SVP) and the deep capillary plexus (DCP), using OCT-A before (normal breathing) and during breathing of the gas mixtures. Retinal vessel calibres in major retinal vessels were measured using a dynamic vessel analyzer. During 100% oxygen breathing, a significant decrease in DCP perfusion density from 41.7 ± 2.4 a.u to 35.6 ± 3.1 a.u. (p < 0.001) was observed, which was accompanied by a significant decrease in vessel diameters in major retinal arteries and veins (p < 0.001 each). No significant change in perfusion density in the SVP occurred (p = 0.33). In contrast, during hypoxia, perfusion density in the SVP significantly increased from 34.4 ± 3.0 a.u. to 37.1 ± 2.2 a.u. (p < 0.001), while it remained stable in the DCP (p = 0.25). A significant increase in retinal vessel diameters was found (p < 0.01). Systemic oxygen saturation correlated negatively with perfusion density in the SVP and the DCP and retinal vessel diameters (p < 0.005 each). Our results show that systemic hyperoxia induces a significant decrease in vessel density in the DCP, while hypoxia leads to increased vessel density limited to the SVP. These results indicate that the retinal circulation shows the ability to adapt its blood flow to metabolic changes with high local resolution dependent on the capillary plexus.

A Peptide/MicroRNA-31 nanomedicine within an electrospun biomaterial designed to regenerate wounds in vivo

microRNA-31 (miR-31) has been identified to be downregulated in pathologies associated with delayed wound repair. Thus, it was proposed that the delivery of a plasmid encoding miR-31 (pmiR-31) to the skin could hold potential in promoting wound healing. Effective delivery of pmiR-31 was potentiated by encapsulation with the CHAT peptide to form nanocomplexes, this improved cellular entry and elicited a potent increase in miR-31 expression in vitro in both skin human keratinocyte cell line (HaCaT) and human microvascular endothelial cell line (HMEC-1). Transfection efficiencies with CHAT/pEFGP-N1 were significant at 15.2 ± 8.1% in HMEC-1 cells and >40% in HaCaT cells. In this study, the CHAT/pmiR-31 nanocomplexes at a N:P ratio of 10 had an average particle size of 74.2 nm with a cationic zeta potential of 9.7 mV. Delivery of CHAT/pmiR-31 to HaCaT and HMEC-1 cells resulted in significant improvements in cell migration capacity and increased angiogenesis. In vivo studies were conducted in C57BL/6 J mice were CHAT/pmiR-31 was delivered via electrospun PVA nanofibres, demonstrating a significant increase in epidermal (increase of ∼38.2 µm) and stratum corneum (increase of 8.2 µm) layers compared to controls. Furthermore, treatment in vivo with CHAT/pmiR-31 increased angiogenesis in wounds compared to controls, with a significant increase in vessel diameter by ∼20.4 µm compared against a commercial dressing control (Durafiber™). Together, these data demonstrate that the delivery of CHAT/pmiR-31 nanocomplexes from electrospun PVA nanofibres represent an innovative therapy for wound repair, eliciting a positive therapeutic response across both stromal and epithelial tissue compartments of the skin. Statement of significanceThis study advances research regarding the development of our unique electrospun nanofibre patch to deliver genetic nanoparticles into wounds in vivo to promote healing. The genetic nanoparticles are comprised of: (a) plasmid micro-RNA31 that has been shown to be downregulated in pathologies with delayed wound repair and (b) a 15 amino acid linear peptide termed CHAT. The CHAT facilitates complexation of miR-31 and cellular uptake. Herein, we report for the first time on the use of CHAT to deliver a therapeutic cargo pmiR-31 for wound healing applications from a nanofibre patch. Application of the nanofibre patch resulted in the controlled delivery of the CHAT/pmiR-31 nanoparticles with a significant increase in both epidermal and stratum corneum layers compared to untreated and commercial controls.

Levosimendan-induced venodilation is mediated by opening of potassium channels.

Unique vascular responses adhere to the cardiovascular efficacy of the inodilator levosimendan. In particular, selective venodilation appears to explain its clinical benefit during pulmonary hypertension complicated by heart failure with preserved ejection fraction. Vasodilators increase vessel diameter in various parts of the vascular system to different degrees and thereby influence blood pressure, its distribution, and organ perfusion depending on their mechanisms of action. Levosimendan and its long‐lived active metabolite OR‐1896 mobilize a set of vasodilatory mechanisms, that is, the opening of the ATP‐sensitive K+ channels and other K+ channels on top of a highly selective inhibition of the phosphodiesterase III enzyme. A vessel‐specific combination of the above vasodilator mechanisms—in concert with cardiac effects and cardiovascular reflex regulations—illustrates the pharmacological profile of levosimendan in various cardiovascular disorders. While levosimendan has been known to be an inotrope, its properties as an activator of ATP‐sensitive K+ channels have gone largely ignored with respect to clinical applications. Here, we provide a summary of what is known about the ATP‐sensitive K+ channel properties in preclinical studies and now for the first time, its ATP‐sensitive K+ channel properties in a clinical trial.

The Effect of Very Low Concentrations of Ethanol on Microvascular Artery and Vein Anastomosis: An Experimental Study

Objectives This study investigated the effect of very low concentrations of ethanol on artery and vein anastomosis. Also, it was aimed to determine the appropriate ethanol concentration to be used in vasospasm. Methods Rats were divided into five groups of eight rats, each group, as follows: Group i: saline; Group ii: 2.5% ethanol; Group iii: 5% ethanol; Group IV: 7.5% ethanol; and Group V: 10% ethanol. During the femoral artery and vein anastomosis, 1ml of the agent was used for irrigation in each group. Vessel diameters were measured before the anastomosis, at the fifth and 15th minutes, and the third week after the anastomosis. Histopathological samples were taken in the third week. Results In Groups ii and iii, the mean vessel diameters were found to increase 15th minute. Also observed was an increase in mean vessel diameter that continued in the third week. Although acute vasodilation was detected in Groups IV and V, arterial and venous thrombosis was observed in the third week. Intima and media thickness decreased in Group ii, while it increased in Group iii. Perivascular inflammation and fibrosis increased as the ethanol concentration increased. Conclusion 2.5% ethanol causes acute and prolonged vasodilation and does not cause endothelial cell damage, perivascular inflammation, and fibrosis. 2.5% ethanol will be a powerful alternative use in many situations that occur with vasospasm.

Comparison of the Effect of High-Intensity Laser Therapy (HILT) on Skin Surface Temperature and Vein Diameter in Pigmented and Non-Pigmented Skin in Healthy Racehorses.

Simple SummaryHigh-intensity laser therapy (HILT) is used in the treatment of horses, but little is known about the differences in the impact of HILT performed on pigmented and non-pigmented skin. The aim of this study was to assess differences in the influence of HILT on skin surface temperature and vein diameter in a group of healthy racehorses with pigmented and non-pigmented skin in the treatment area. The hypothesis was that HILT would cause a greater increase in skin surface temperature and vein diameter in horses with pigmented skin compared to non-pigmented skin. Ten Thoroughbreds with pigmented skin and ten Thoroughbreds with non-pigmented skin in the treatment area received HILT. Changes in the vein diameter and skin surface temperature of the irradiated area were measured before and after HILT. The HILT treatment caused an increase in the pigmented skin surface temperature and a decrease in the non-pigmented skin surface temperature, while the vein diameter increased in both groups. In conclusion, melanin content in the epidermis plays an important role in light energy absorption and photothermal effects. Determining the physiological and clinical effects of HILT performed on pigmented and non-pigmented skin will help clinicians choose appropriate HILT parameters.The aim of the study was to assess differences in the influence of high-intensity laser therapy (HILT) on the skin surface temperature and vein diameter of the lateral fetlock joint region in a group of racehorses with pigmented and non-pigmented skin in the treatment area. Twenty Thoroughbreds were divided into two equal groups: pigmented and non-pigmented skin groups. Each horse received the same HILT treatment. Just before and immediately after HILT, thermographic examination was performed to measure the skin surface temperature and ultrasonographic examination assessed the lateral digital palmar vein diameter. After HILT, the pigmented skin surface temperature increased, while the non-pigmented skin surface temperature decreased, and the difference between both groups was significant (p < 0.001). The vein diameter increased after HILT in horses with pigmented and non-pigmented skin, but the difference between both groups was not significant (p = 0.14). In conclusion, melanin content in the epidermis plays an important role in light energy absorption and photothermal effects. The vein diameter changes after HILT application indicated that the increase in vessel diameter may partly depend on photothermal mechanisms occurring in irradiated tissue. Further research is necessary to describe the physiological and clinical effects of HILT performed on pigmented and non-pigmented skin.

ANATOMICAL RADIAL VARIATION AND DENSITY IN WOOD OF RUBBER TREE [Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.] CLONES

The anatomical structure and physical properties of wood change signifcantly among trees of the same species and even among different parts of the same tree. However, studies that characterize radial variation of anatomical characteristics and wood density among clones are scarce, specifcally for the rubber tree [Hevea brasiliensis (Will. ex Adr. De Juss.) Muell]. Thus, the objective of the research was evaluating the anatomical radial variation and density in wood of Hevea brasiliensis clones. For this study, 30 trees, three of each progeny from 10 clones were used. For most clones, we noticed an increase in fber length and vessel diameter towards the bark. For vessel frequency, ray height, width and frequency, we observed a decrease towards the bark. Fiber wall thickness was the most distinctive anatomical characteristic, compared to the others, presenting a trend of thicker walls in the middle position, consequently infuencing basic density clones.

Pulmonary Arterial Remodeling Is Related to the Risk Stratification and Right Ventricular-Pulmonary Arterial Coupling in Patients With Pulmonary Arterial Hypertension.

BackgroundPulmonary arterial (PA) stiffness has an essential contribution to the right ventricular (RV) failure pathogenesis. A comprehensive and multiparameter risk assessment allows predicting mortality and guiding treatment decisions in PA hypertension (PAH). We characterize PA remodeling with intravascular ultrasound (IVUS) in prevalent and stable patients with PAH according to the ESC/ERS risk table and analyze the RV-PA coupling consequences.MethodsTen control subjects and 20 prevalent PAH adult patients underwent right heart catheterization (RHC) with simultaneous IVUS study. We estimated cardiac index (CI), pulmonary vascular resistance, and compliance (PVR, PAC) by standard formulas. From IVUS and RHC data, PA diameter, wall thickness/luminal diameter ratio, and indexes of stiffness (pulsatility, compliance, distensibility, incremental elastic modulus - Einc-, and the stiffness index β) were measured. We evaluated RV-PA coupling by the ratio of tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (TAPSE/sPAP). The individual average risk was calculated by assigning a score of 1 (low-risk -LR-), 2 (intermediate-risk -IR-), and 3 (high-risk -HR-) for each of seven variables (functional class, six-minute walking test, brain natriuretic peptide, right atrial area and pressure, CI, and PA oxygen saturation) and rounding the average value to the nearest integer.ResultsAll PA segments interrogated showed increased vessel diameter, wall cross-sectional area (WCSA), and stiffness in patients with PAH compared to control subjects. 45% corresponded to LR, and 55% corresponded to IR PAH patients. The different measurements of PA stiffness showed significant correlations with TAPSE/sPAP (r = 0.6 to 0.76) in PAH patients. The IR group had higher PA stiffness and lower relative WCSA than LR patients (P < 0.05), and it is associated with a lower PAC and TAPSE/sPAP (P < 0.05).ConclusionIn prevalent PAH patients, the severity of proximal PA remodeling is related to the risk stratification and associated with PAC and RV-PA coupling impairment beyond the indirect effect of the mean PA pressure. The concomitant assessment of IVUS and hemodynamic parameters at diagnosis and follow-up of PAH patients could be a feasible and safe tool for risk stratification and treatment response of the PA vasculopathy during serial hemodynamic measurements.