Relaxation Response Research Articles

Chronic anemia is associated with systemic endothelial dysfunction.

In acute myocardial infarction and heart failure, anemia is associated with adverse clinical outcomes. Endothelial dysfunction (ED) is characterized by attenuated nitric oxide (NO)-mediated relaxation responses which is poorly studied in chronic anemia (CA). We hypothesized that CA is associated with ED due to increased oxidative stress in the endothelium. CA was induced by repeated blood withdrawal in male C57BL/6J mice. Flow-Mediated Dilation (FMD) responses were assessed in CA mice using ultrasound-guided femoral transient ischemia model. Tissue organ bath was used to assess vascular responsiveness of aortic rings from CA mice, and in aortic rings incubated with red blood cells (RBCs) from anemic patients. In the aortic rings from anemic mice, the role of arginases was assessed using either an arginase inhibitor (Nor-NOHA) or genetic ablation of arginase 1 in the endothelium. Inflammatory changes in plasma of CA mice were examined by ELISA. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), myeloperoxidase (MPO), 3-Nitrotyrosine levels, and 4-Hydroxynonenal (4-HNE) were assessed either by Western blotting or immunohistochemistry. The role of reactive oxygen species (ROS) in ED was assessed in the anemic mice either supplemented with N-Acetyl cysteine (NAC) or by in vitro pharmacological inhibition of MPO. The FMD responses were diminished with a correlation to the duration of anemia. Aortic rings from CA mice showed reduced NO-dependent relaxation compared to non-anemic mice. RBCs from anemic patients attenuated NO-dependent relaxation responses in murine aortic rings compared to non-anemic controls. CA results in increased plasma VCAM-1, ICAM-1 levels, and an increased iNOS expression in aortic vascular smooth muscle cells. Arginases inhibition or arginase1 deletion did not improve ED in anemic mice. Increased expression of MPO and 4-HNE observed in endothelial cells of aortic sections from CA mice. NAC supplementation or inhibition of MPO improved relaxation responses in CA mice. Chronic anemia is associated with progressive endothelial dysfunction evidenced by activation of the endothelium mediated by systemic inflammation, increased iNOS activity, and ROS production in the arterial wall. ROS scavenger (NAC) supplementation or MPO inhibition are potential therapeutic options to reverse the devastating endothelial dysfunction in chronic anemia.

Vasorelaxant property of 2-phenyl ethyl alcohol isolated from the spent floral distillate of damask rose (Rosa damascena Mill.) and its possible mechanism

Ethnobotanical relevanceRosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits. Aim of the studyThis study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil. Materials and methodsThe freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored. ResultsThe SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BKCa channel was found to be the major target for PEA-induced relaxation response in these blood vessels. ConclusionsThe spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension.

Intravenous administration of apeling-13 induces a depressor response by releasing an unidentified substance

Apelin and APJ receptor play an important role in the regulating cardiovascular function; however, conflicting results have been reported regarding the effect of apelin on cardiovascular regulation. In this study, blood pressure and heart rate were measured by femoral arterial catheterization; and cardiac contractility was recorded by left ventricular catheterization through the right carotid artery in rats before and after intravenous administration of [pyr1]-apelin-13. The results show that intravenous administration of apelin-13 caused a dramatic reduction in BP but did not significantly alter heart rate and contractility. To study the mechanism of the apelin-induced depressor response, isometric tension was measured in isolated mesenteric arteries using a myograph approach. Surprisingly, treatment of the arteries with [pyr1]-apelin-13 did not cause relaxation of mesenteric arteries preconstricted with norepinephrine; however, treatment with plasma collected from rats that received intravenous administration of [pyr1]-apelin-13 caused pronounced relaxation of isolated arteries. Incubation with the guanylyl cyclase inhibitor, ODQ, blocked NO-induced relaxation, but did not significantly alter the relaxation response to the plasma from apelin-treated rats. Taken together, these findings demonstrate that intravenous injection of apelin causes a significant depressor response that is mediated by a NO-independent mechanism involving an unidentified substance released into the bloodstream leading to vasodilation.

Phosphodiesterase type 9 opposes relaxation of mouse pulmonary artery but does not influence chronic hypoxia-induced pulmonary hypertension in mouse

PDE9 is a phosphodiesterase which has recently emerged as a regulator of cGMP in cardiac and vascular myocytes. Its contribution in vasculature is, however, unclear. We sought to investigate PDE9 expression and function in mouse pulmonary artery by comparing wild type (WT) and PDE9-deficient, Pde9a(-/-), mice. We also addressed the hypothesis that PDE9 could represent a new therapeutic target to treat pulmonary arterial hypertension, a severe, deadly disease. PDE9 expression was examined in mouse tissues and human pulmonary artery from subjects with or without pulmonary arterial hypertension using RT-PCR and immunoblots. Relaxant responses were studied in mouse pulmonary arteries mounted on a myograph and contracted with phenylephrine. A challenge with 21-day, 10% O2-hypoxia was used as a model of pulmonary hypertension in mice and was compared to normoxia. Right ventricle and pulmonary artery morphology and function were determined by echocardiography, right ventricle catheterization and gravimetric analysis. PDE9 protein and Pde9a transcript were detected in human and mouse pulmonary arteries, respectively. Pulmonary arteries from Pde9a(-/-) mice displayed more potent relaxant responses to acetylcholine, to the NO donor diethylamine NONOate and to atrial natriuretic peptide than vessels from WT animals. Following hypoxia, Pde9a expression was increased in lung and right ventricle from WT mice. PDE9 deficiency failed to ameliorate pulmonary hypertension hemodynamic criteria, namely higher right ventricular systolic pressure and lower echocardiographic pulmonary arterial acceleration time. Right ventricle hypertrophy, reflected by increased Fulton index, right ventricle thickness and fetal genes expression, were also similar in Pde9a(-/-) and WT groups. PDE9 is expressed in pulmonary artery and takes part in the relaxant responses mediated by the cGMP pathway. The ablation of Pde9a in mouse, however, does not prevent the development of pulmonary hypertension in a 21-day hypoxia model, nor does it attenuate right ventricle deleterious remodeling.

Experimental Study on the Time-Dependent Oedometric Compression Behavior of Calcareous Sand

A series of compression tests were carried out on two types of calcareous sand to study the time-dependent behavior of calcareous sand under oedometric conditions. Consolidation, creep, stress relaxation, and constant strain/stress rate tests were conducted. At the same time, the effects of input energy and grain shape on particle breakage were investigated. The test results show that a large amount of particle breakage occurs in the calcareous soils under different modes of loading, leading to a significant time effect on the oedometric compression responses. Under the same level of vertical stress, the large-grain calcareous sand has a higher creep or relaxation rate. Over-consolidated sand has a much smaller creep or relaxation response than normally consolidated sand, and the response decreases with an increase in the overconsolidation ratio. Loading rate has an influence on the compressibility of calcareous sand, especially when the particle breakage is significant. In addition, it is also shown that a unique relationship exists between the relative breakage and the input energy for the same kind of calcareous sand, which is independent of the loading mode.

Combined levothyroxine and testosterone treatment for restoring erectile dysfunction in propylthiouracil-induced hypothyroid rats.

Sexual dysfunction may indicate severe endocrine diseases. Recent research has suggested a link between hypothyroidism, low testosterone (T) levels, and erectile dysfunction (ED); however, the exact cause is unknown. We sought to investigate possible beneficial effects of levothyroxine and T alone or in combination on ED in propylthiouracil (PTU)-induced hypothyroid rats. Adult Wistar rats (n = 35) were divided into 5 groups: control, PTU-induced hypothyroidism, PTU + levothyroxine, PTU + Sustanon (a mixture of 4 types of T: propionate, phenylpropionate, isocaproate, and decanoate) and PTU + levothyroxine + Sustanon. PTU was given in drinking water for 6 weeks. Four weeks after PTU administration, levothyroxine (20μg microgram kg/day, oral) and Sustanon (10mg/kg/week, intramuscular) were given for 2weeks. Serum levels of total T, triiodothyronine (T3), and thyroxine (T4) were determined. In vivo erectile response and in vitro relaxant responses were measured. Localization of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and phosphodiesterase type 5 (PDE5) were determined using immunohistochemical analysis. The relative area of smooth muscle to collagen was measured using Masson trichrome staining. Outcome variables included in vivo erectile function, in vitro relaxant and contractile responses of corpus cavernosum (CC) strips; protein localization of eNOS, nNOS, and PDE5; and smooth muscle content in penile tissue. The rat model of hypothyroidism showed a significant decline in serum levels of total T, T3, and T4. Levothyroxine increased T3 and T4 levels, whereas Sustanon normalized only total T levels. Combined treatment enhanced all hormone levels. Rats with hypothyroidism displayed the lowest erectile response (P < 0.001 vs controls). Combined treatment returned reduced responses, while partial amelioration was observed after levothyroxine and Sustanon treatment alone. Acetylcholine (P < 0.01 vs controls), electrical field stimulation (P < 0.001 vs controls), and sildenafil-induced relaxant responses (P < 0.05 vs controls) were decreased in the CC strips from hypothyroid rats. The combined treatment increased the reduction in relaxation responses. Levothyroxine and Sustanon restored decreases in eNOS and nNOS expression in the hypothyroid group. There was no significant difference in PDE5 expression among groups. Monotreatment partially enhanced reduced smooth muscle mass, while combined therapy completely recovered. The combination of thyroid hormones and T is likely to be a therapeutic approach for treatment of hypothyroidism-induced ED in men. Beneficial effects of levothyroxine and Sustanon treatment were shown in vitro and in vivo in PTU-induced hypothyroid rats. The main limitation of the study was the lack of measurement of androgen-sensitive organ weights and luteinizing hormone, follicle-stimulating hormone, and prolactin levels. These findings demonstrate that neurogenic and endothelium-dependent relaxation responses are reduced by hypothyroidism, which is detrimental to T levels and erectile responses. Levothyroxine and Sustanon combination medication was able to counteract this effect.

Serum from Men with the Severe Form of COVID-19 Impairs the Nitric Oxide Signaling Pathway in Isolated Corpus Cavernosum from Mice: An In Vitro Study

Introduction. Erectile dysfunction (ED) is characterized by the inability to achieve and/or maintain an erection during sexual activity. Vascular-related diseases such as obesity, diabetes, aging, and hypertension are known risk factors that increase the prevalence of ED. The viral infection caused by SARS-CoV-2, the etiological agent of COVID-19, can evolve into mild to severe forms. Patients with comorbidities such as diabetes and obesity present a more severe state of the disease. The cytokine storm and reactive oxygen species associated with COVID-19 can lead to progressive systemic inflammation and vascular dysfunction. This study is aimed at assessing the in vitro effects of serum obtained from unvaccinated men who had the severe form of COVID-19 in isolated corpus cavernosum (CC) from healthy mice. Methods. Concentration-response curves to endothelium-dependent and endothelium-independent substances were carried out in isolated CC from mice after being incubated (3 hours) with serum obtained from patients with and without (control group) the severe form of COVID-19. qRT-PCR and western blotting were also carried out. Results. The relaxing responses induced by acetylcholine (ACh), a nitric oxide donor (sodium nitroprusside), soluble guanylate cyclase (sGC) stimulator (BAY 63-2521), and phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) were significantly reduced in CC incubated with COVID-19 serum when compared with CC incubated with the control serum. Nonetheless, the relaxation induced by the sGC activator BAY 58-2667 was unaffected in CC stimulated with the COVID-19 serum. The coincubation of control or COVID-19 serum with a free radical scavenger (PEG-SOD; 150 UI/mL, 3 hours) significantly improved the relaxation induced by ACh. On the other hand, catalase did not improve ACh-induced relaxation in CC incubated with the sera. The gene expression for PDE5 and NADPH oxidase type 4 was increased in CC stimulated with COVID-19 serum in comparison to tissues stimulated with the control serum. The protein expression for sGC subunits was similar in both groups. Conclusion. Serum obtained from unvaccinated men who presented the severe form of COVID-19 impaired the relaxation induced by cyclic guanosine monophosphate-accumulating substances in CC from mice.

Photosynthetic response dynamics in the invasive species Tithonia diversifolia and two co-occurring native shrub species under fluctuating light conditions

To determine the invasiveness of invasive plants, many studies have compared photosynthetic traits or strategies between invasive and native species. However, few studies have compared the photosynthetic dynamics between invasive and native species during light fluctuations. We compared photosynthetic induction, relaxation dynamics and leaf traits between the invasive species, Tithonia diversifolia and two native species, Clerodendrum bungei and Blumea balsamifera, in full-sun and shady habitats. The photosynthetic dynamics and leaf traits differed among species. T. diversifolia showed a slower induction speed and stomatal opening response but had higher average intrinsic water-use efficiency than the two native species in full-sun habitats. Thus, the slow induction response may be attributed to the longer stomatal length in T. diversifolia. Habitat had a significant effect on photosynthetic dynamics in T. diversifolia and B. balsamifera but not in C. bungei. In shady habitat, T. diversifolia had a faster photosynthetic induction response than in full-sun habitat, leading to a higher average stomatal conductance during photosynthetic induction in T. diversifolia than in the two native species. In contrast, B. balsamifera had a larger stomatal length and slower photosynthetic induction and relaxation response in shady habitat than in full-sun habitat, resulting in higher carbon gain during photosynthetic relaxation. Nevertheless, in both habitats, T. diversifolia had an overall higher carbon gain during light fluctuations than the two native species. Our results indicated that T. diversifolia can adopt more effective response strategies under fluctuating light environments to maximize carbon gain, which may contribute to its successful invasion.

Effect of Copper Segregation at Low-Angle Grain Boundaries on the Mechanisms of Plastic Relaxation in Nanocrystalline Aluminum: An Atomistic Study.

The paper studies the mechanisms of plastic relaxation and mechanical response depending on the concentration of Cu atoms at grain boundaries (GBs) in nanocrystalline aluminum with molecular dynamics simulations. A nonmonotonic dependence of the critical resolved shear stress on the Cu content at GBs is shown. This nonmonotonic dependence is related to the change in plastic relaxation mechanisms at GBs. At a low Cu content, GBs slip as dislocation walls, whereas an increase in Cu content involves a dislocation emission from GBs and grain rotation with GB sliding.

Designing Viscoelastic Gelatin-PEG Macroporous Hybrid Hydrogel with Anisotropic Morphology and Mechanical Properties for Tissue Engineering Application

The mechanical properties of scaffolds play a vital role in regulating key cellular processes in tissue development and regeneration in the field of tissue engineering. Recently, scaffolding material design strategies leverage viscoelasticity to guide stem cells toward specific tissue regeneration. Herein, we designed and developed a viscoelastic Gel-PEG hybrid hydrogel with anisotropic morphology and mechanical properties using a gelatin and functionalized PEG (as a crosslinker) under a benign condition for tissue engineering application. The chemical crosslinking/grafting reaction was mainly involved between epoxide groups of PEG and available functional groups of gelatin. FTIR spectra revealed the hybrid nature of Gel-PEG hydrogel. The hybrid hydrogel showed good swelling behavior (water content &gt; 600%), high porosity and pore interconnectivity suitable for tissue engineering application. Simple unidirectional freezing followed by a freeze-drying technique allowed the creation of structurally stable 3D anisotropic macroporous architecture that showed tissue-like elasticity and was capable of withstanding high deformation (50% strain) without being damaged. The tensile and compressive modulus of Gel-PEG hybrid hydrogel were found to be 0.863 MPa and 0.330 MPa, respectively, which are within the range of normal human articular cartilage. In-depth mechanical characterizations showed that the Gel-PEG hybrid hydrogel possessed natural-tissue-like mechanics such as non-linear and J-shaped stress-strain curves, stress softening effect, high fatigue resistance and stress relaxation response. A month-long hydrolytic degradation test revealed that the hydrogel gradually degraded in a homogeneous manner over time but maintained its structural stability and anisotropic mechanics. Overall, all these interesting features provide a potential opportunity for Gel-PEG hybrid hydrogel as a scaffold in a wide range of tissue engineering applications.

Nafion-Pt IPMC electroactive behavior changes in response to environmental nonequilibrium conditions

Electroactive polymers (EAPs) continue to gain attention for their potential to offer unique and versatile solutions in the soft robotic and flexible electronic industries. Ionic polymer-metal composites (IPMCs) are a class of ionic-type EAPs which can be configured as capacitor actuators with very low voltage requirements (⩽5 V AC or DC). Their compact, portable, and lightweight properties, coupled with a biomimetic bending actuation response make them ideal for human-machine integrated technologies such as medical implants, active skins, and artificial muscles. This work tested the IPMC’s actuation and electrical response in varying saturation conditions (70% RH, 85% RH, 95% RH, and DI water liquid immersion) and voltage application schemes (direct current voltage (DCV) cycled, continuously applied, and relaxation responses upon voltage removal). This information was then used to establish actuation and back-relaxation response patterns through repetitive testing for statistical certainty. These demonstrated maximized actuation in water vapor conditions where the IPMC’s dielectric permittivity is maximized (), and the dissipation factor is minimized (). The response trends in vapor conditions are gradual but yield larger actuation ranges with increasing hydration. Liquid immersion restricts the IPMC’s range of motion but produces a sharper response pattern. These trends were validated against previously published IPMC actuator models. All of this creates a more pragmatic perspective on the potential of this technology which aids in the advancement of this material’s evolution towards viable real-world application configurations which capitalize on the material’s natural responses.

MP27-06 BROMELAIN INDUCES RELAXATION OF HUMAN CORPUS CAVERNOSUM TISSUE IN VITRO INDEPENDENT NITRIC OXIDE-CGMP PATHWAY: POSSIBLE SIGNIFICANCE FOR ERECTILE DYSFUNCTION

You have accessJournal of UrologyCME1 Apr 2023MP27-06 BROMELAIN INDUCES RELAXATION OF HUMAN CORPUS CAVERNOSUM TISSUE IN VITRO INDEPENDENT NITRIC OXIDE-CGMP PATHWAY: POSSIBLE SIGNIFICANCE FOR ERECTILE DYSFUNCTION Serap Gur, Suresh C. Sikka, Asim B. Abdel-Mageed, Didem Yilmaz-Oral, Sudha Talwar, and Wayne J.G. Hellstrom Serap GurSerap Gur More articles by this author , Suresh C. SikkaSuresh C. Sikka More articles by this author , Asim B. Abdel-MageedAsim B. Abdel-Mageed More articles by this author , Didem Yilmaz-OralDidem Yilmaz-Oral More articles by this author , Sudha TalwarSudha Talwar More articles by this author , and Wayne J.G. HellstromWayne J.G. Hellstrom More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bromelain (BRM) is a mixture of proteolytic enzymes found in several parts of the pineapple (Ananas comosus) plant. BRM is widely administered for its well-recognized properties, mainly anti-inflammatory, antithrombotic and fibrinolytic, anticancer, and immunomodulatory. BRM gained universal acceptance as a phytotherapeutic agent due to its extensive dietary usage and lack of side effects; however, the complete molecular mechanism of action of BRM has not been completely identified. This exploratory study focuses on the erectile responses of human cavernosal strips on isometric tension measurements. In this study, we aimed to evaluate the effectiveness of (a) pure BRM (from pineapple stem, Sigma-Aldrich, St Louis, MO), (b) BRM dietary supplement (BG, Natural Brand Bromelain 500mg tablet, GNC, Pittsburgh, PA) and (c) fresh pineapple juice (PAJ) on human corpus cavernosum (HCC). METHODS: HCC tissues were obtained from men undergoing penile prosthesis implantation (n =8-10) and prepared for organ bath experiments as per our published procedures. BRM-induced relaxation response (10-8-10-3 M) was performed in vitro using HCC strips in an organ bath. The effects of inhibitors [NG-nitro-L-arginine methyl ester (L-NAME, 100µM), 1H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10one (ODQ, 30µM), and tetraethylammonium (TEA, 100 µM, blocker Ca2+ - activated K+channels)] on BRM-mediated relaxation responses were evaluated. The relaxation effects of BRM, BG, and PAJ on phenylephrine (Phe)-induced contraction were also compared. The protein expression of endothelial (e) and neuronal (n) nitric oxide synthase (NOS) and vascular endothelium growh factor (VEGF) were determined using Western blotting and immunohistochemistry. RESULTS: BRM inhibited Phe-evoked contractions in a dose-dependent manner. All agents induced relaxation of HCC (maximum response: BRM- 62.87 ± 6.23%, BG - 61.95 ± 4.17%, PAJ -55.68 ± 5.52%) after Phe-contraction. Inhibitors of nitric oxide (L-NAME) and soluble guanylate cyclase (ODQ) as well as TEA failed to affect the BRM-induced HCC relaxations. The relaxant responses of HCC strips were observed in the presence or the absence of BRM products. Furthermore, eNOS and nNOS protein levels were decreased and were not restored after BRM, while VEGF levels remained unaltered. CONCLUSIONS: These data suggest that BRM have the capacity to exert in vitro penile relaxations. The underlying mechanism of BRM is likely independent of the nitric oxide-cyclic guanosine monophosphate pathway. Overall, these in vitro studies suggested that consumption of BRM and its supplements may represent a novel strategy to prevent and treat erectile dysfunction in men, especially due to inflammatory issues. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e364 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Serap Gur More articles by this author Suresh C. Sikka More articles by this author Asim B. Abdel-Mageed More articles by this author Didem Yilmaz-Oral More articles by this author Sudha Talwar More articles by this author Wayne J.G. Hellstrom More articles by this author Expand All Advertisement PDF downloadLoading ...

The Effect of Blending Natural Rubber‐graft‐poly(methyl methacrylate) on the Dielectric Relaxation of Poly(ethylene oxide)

AbstractThis study focuses on the dielectric relaxation of the immiscible PEO/NR‐g‐PMMA blends. Due to the heterogeneous morphologies of the blends, the molecular mobility in the polymer chains displays various relaxation responses. The dielectric relaxation of the blends is analyzed in terms of complex impedance, complex permittivity, tangent loss spectra, and complex modulus. The molten neat PEO promotes a long‐range conduction mechanism. On the other hand, NR‐g‐PMMA displays the relaxation of short‐range motion only at temperatures above the glass transition temperature of PMMA‐graft. As for the blends, the relaxation of the dipoles proceeds slower and broader dispersion of relaxation times occurs when NR‐g‐PMMA is added to PEO. In the molten state, only blends with an excess of PEO display the dominance of the long‐range motion of the dipolar entities. The short‐range motion of the dipolar entities becomes dominant when NR‐g‐PMMA is in excess. This suggests that the high restriction of dipole motions in NR‐g‐PMMA affects the dielectric relaxation behavior of PEO/NR‐g‐PMMA blends.

Theophylline-Induced Relaxation Is Enhanced after Testosterone Treatment via Increased KV1.2 and KV1.5 Protein Expression in Guinea Pig Tracheal Smooth Muscle.

Theophylline is a drug commonly used to treat asthma due to its anti-inflammatory and bronchodilatory properties. Testosterone (TES) has been suggested to reduce the severity of asthma symptoms. This condition affects boys more than girls in childhood, and this ratio reverses at puberty. We reported that guinea pig tracheal tissue chronic exposure to TES increases the expression of β2-adrenoreceptors and enhances salbutamol-induced K+ currents (IK+). Herein, we investigated whether the upregulation of K+ channels can enhance the relaxation response to methylxanthines, including theophylline. Chronic incubation of guinea pig tracheas with TES (40 nM, 48 h) enhanced the relaxation induced by caffeine, isobutylmethylxanthine, and theophylline, an effect that was abolished by tetraethylammonium. In tracheal myocytes, chronic incubation with TES increased theophylline-induced IK+; flutamide reversed this effect. The increase in IK+ was blocked by 4-aminopyridine by ~82%, whereas iberiotoxin reduced IK+ by ~17%. Immunofluorescence studies showed that chronic TES exposure increased the expression of KV1.2 and KV1.5 in airway smooth muscle (ASM). In conclusion, chronic exposure to TES in guinea pig ASM promotes upregulation of KV1.2 and KV1.5 and enhances theophylline relaxation response. Therefore, gender should be considered when prescribing methylxanthines, as teenage boys and males are likely to respond better than females.

Effect Effect of Foot Massage Therapy on Patient’s Non-Invasive Hemodynamic Status in The Intensive Care Unit

Intensive care is a care service for critical, acute, and life-threatening patients with hemodynamic instability. The use of a ventilator can make discomfort to the patients and then affect the patient's hemodynamics. Foot massage can be applied to intensive patients. This study aims to determine the effect of foot massage on non-invasive hemodynamic status patients in the ICU of the Sanglah General Public Hospital. The quasi-experimental design with a time series approach used, involve 12 patients using a purposive sampling technique. A foot massage was carried out for 30 minutes and hemodynamic measurements were taken 30 minutes later. The research data were analyzed using the Friedman test then continued with the post-hoc Wilcoxon Sign Rank test analysis. Foot massage therapy was given a significant effect on non-invasive hemodynamic status in patients in ICU, including decreasing respiratory frequency (p=0.002), decreasing MAP (p=0.002), decreasing heart rate (p=0.002), and increasing oxygen saturation (p=0.002). It provides a relaxation response that stimulates the sympathetic nervous system to decrease its activity and increase the work of the parasympathetic nerves which influence decreasing heart rate and blood pressure so that there is a balance between oxygen and carbon dioxide in the tissues then reduce the respiratory rate to become normal.

Evaluation of coronary function in female rats with severe type 1 diabetes: Effects of combined treatment with insulin and pyridoxamine.

This study aimed to evaluate the coronary function, myocardium, and epicardial adipose tissue (EAT) in female rats with severe type 1 diabetes and the effects of combined treatment with insulin and pyridoxamine (AGEs inhibitor). Female Wistar rats were divided into groups: control (CTR, n=13), type 1 diabetes (DM1, n=12), type 1 diabetes treated with insulin (DM1+INS, n=11), and type 1 diabetes treated with insulin and pyridoxamine (DM1+INS+PDX, n=14). The vascular responsiveness was performed in the septal coronary artery and the protein expressions of AGE, RAGE, GPER, NF-kB was evaluated in the left ventricle (LV), as well as the reactive oxygen species (ROS) was measured in LV and in EAT. We analyzed plasma levels of glucose, estradiol, Nε-carboxymethylisine (CML), thiobarbituric acid reactive substances (TBARS), catalase (CAT), and superoxide dismutase (SOD). The maximal responses to ACh were reduced in the DM1 compared with the CTR group, accompanied by an increase in circulating glucose, CML, and TBARS. Additionally, the expression of NF-kB in LV and generation of ROS in the presence of MnTMPyP (SOD mimetic) were increased in the DM1 group compared with CTR. Only the combined treatment was effective for fully re-establish ACh relaxation response, NF-kB protein expression, ROS generation, and increased SOD activity in the DM1+INS+PDX group. The reduction of the endothelium-dependent relaxation response in the septal coronary artery of female rats with severe type 1 diabetes was normalized with the combined treatment with insulin and pyridoxamine, associated with reduced inflammation and oxidative stress in the myocardium and increased circulating antioxidant activity.

The microstructure and dielectric properties of Yb2O3 doped 0.92BaTiO3 - 0.08(Na0.5Bi0.5)TiO3 relaxor ceramics

The dielectric properties and mechanism of xYb2O3 doped 0.92BaTiO3 - 0.08(Na0.5Bi0.5)TiO3 ceramics with x = 0.005–0.025 have been investigated. The addition of 0.015 mol Yb2O3 improves the permittivity and enhance diffuseness of temperature dependent permittivity for 0.92BaTiO3 - 0.08(Na0.5Bi0.5)TiO3, which gives an εr′ variation within ±10 % in 20–170 °C. Core-shell microstructures observed in the grains of samples, which is responsible for the dielectric diffuseness and permittivity of xYb2O3 doped 0.92BaTiO3 - 0.08(Na0.5Bi0.5)TiO3 ceramics. Three different relaxation responses are identified by the impedance analysis as grain boundary, grain shell and grain core responses from the low to high frequency. The Yb2O3 shows neglectable effect to the grain boundary but affects the grain shell and grain core obviously. The Yb3+ are mainly in grain shells as x < 0.015 and distributed both in the grain shell and core region as x ≥ 0.015.

Size- and position-dependent cytoplasm viscoelasticity through hydrodynamic interactions with the cell surface

Many studies of cytoplasm rheology have focused on small components in the submicrometer scale. However, the cytoplasm also baths large organelles like nuclei, microtubule asters, or spindles that often take significant portions of cells and move across the cytoplasm to regulate cell division or polarization. Here, we translated passive components of sizes ranging from few up to ~50 percents of the cell diameter, through the vast cytoplasm of live sea urchin eggs, with calibrated magnetic forces. Creep and relaxation responses indicate that for objects larger than the micron size, the cytoplasm behaves as a Jeffreys material, viscoelastic at short timescales, and fluidizing at longer times. However, as component size approached that of cells, cytoplasm viscoelastic resistance increased in a nonmonotonic manner. Flow analysis and simulations suggest that this size-dependent viscoelasticity emerges from hydrodynamic interactions between the moving object and the static cell surface. This effect also yields to position-dependent viscoelasticity with objects initially closer to the cell surface being harder to displace. These findings suggest that the cytoplasm hydrodynamically couples large organelles to the cell surface to restrain their motion, with important implications for cell shape sensing and cellular organization.

Magnesium ions improve vasomotor function in exhausted rats.

To observe the effect of magnesium ion on vascular function in rats after long-term exhaustive exercise. Forty male SD rats were divided into two groups, the control group (CON group, n = 20) and the exhaustive exercise group (EEE group, n = 20). Exhausted rats performed 1W adaptive swimming exercise (6 times/W, 15min/time), and then followed by 3W formal exhaustive exercise intervention. Hematoxylin and eosin (HE) staining was used to detect the morphological changes of rat thoracic aorta. The contents of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and endothelin 1 (ET-1) in serum of rats were determined by biochemical kit. Vascular ring test detects vascular function. Compared with the CON group, the smooth muscle layer of the EEE group became thicker, the cell arrangement was disordered, and the integrity of endothelial cells was destroyed; the serum Mg2+ in EEE group was decreased; the serum levels of IL-1β, TNF-α, MDA and ROS in EEE group were significantly higher than those in the CON group (P are all less than 0.05); the serum NO content in EEE group was significantly decreased, and the ratio of NO/ET-1 was significantly decreased. In the exhaustion group, the vasoconstriction response to KCl was increased, and the relaxation response to Ach was weakened, while 4.8mM Mg2+ could significantly improve this phenomenon (P are all less than 0.01). The damage of vascular morphology and function in rats after exhaustion exercise may be related to the significant increase of serum IL-1β, TNF-α, ROS, MDA and ET-1/NO ratio in rats after exhaustion exercise, while Mg2+ can significantly improve the vasomotor function of rats after exhaustion exercise.

Phosphodiesterases type 2, 3 and 4 promote vascular tone in mesenteric arteries from rats with heart failure

Phosphodiesterases (PDE) type 3 and 4 promote vasoconstriction by hydrolysing cAMP. In experimental heart failure (HF), PDE3 makes PDE4 redundant in aorta, but it is not known if this occurs in resistance vessels, such as mesenteric artery. As PDE2 is increased in the failing myocardium, its possible role in the vasculature also needs to be addressed. Here, the function of PDE2, PDE3 and PDE4 in rat mesenteric arteries was characterized in experimental HF.Mesenteric arteries were isolated from rats sacrificed 22 weeks after surgical stenosis of the ascending aorta (HF), or Sham surgery. PDE inhibitors were used to probe isoenzyme contributions in enzymatic and isometric tension assays. PDE2 and PDE4 activities, but not PDE3 activity, facilitate contraction produced by the thromboxane analogue U46619 in Sham arteries, while in HF all three isoenzymes contribute to this response. NO synthase inhibition by L-NAME abolished the action of the PDE2 inhibitor. L-NAME eliminated the contribution of PDE4 in HF, but unmasked a contribution for PDE3 in Sham. PDE3 and PDE4 activities attenuated relaxant response to β-adrenergic stimulation in Sham and HF. PDE2 did not participate in cAMP or cGMP-mediated relaxant responses. PDE3 and PDE4 cAMP-hydrolysing activities were smaller in HF mesenteric arteries, while PDE2 activity was scarce in both groups. Endothelial cells and arterial myocytes displayed PDE2 immunolabelling.We highlight that, by contrast with previous observations in aorta, PDE4 participates equally as PDE3 in contracting mesenteric artery in HF. PDE2 activity emerges as a promoter of contractile response that is preserved in HF.