scholarly journals β-Adrenoceptor-Mediated Relaxation of Carbachol-Pre-Contracted Mouse Detrusor

2015 ◽  
Vol 95 (1) ◽  
pp. 92-98 ◽  
Author(s):  
Stefan Propping ◽  
Manja Newe ◽  
Kristina Lorenz ◽  
Manfred P. Wirth ◽  
Ursula Ravens

Aims: To study the β-adrenoceptor subtypes involved in the relaxation responses to (-)-isoprenaline in carbachol-pre-contracted (CCh) mouse detrusor muscle with intact and denuded mucosa. Methods: Isolated muscle strips from the urinary bladder of male C57BL6 mice or β2-adrenoceptor knockout mice were pre-contracted with CCh, 1 µM and relaxed with increasing concentrations of the β-adrenoceptor (β-AR) agonist (-)-isoprenaline and forskolin. For estimating the β-AR subtypes involved, subtype-selective receptor blockers were used, that is, CGP 20712A (β1-ARs), ICI 118,551 (β2-ARs), and L748,337 (β3-ARs). Results: Unlike in KCl-pre-contracted muscle, the mucosa did not affect the sensitivity of the relaxation response to (-)-isoprenaline in CCh-pre-contracted murine detrusor strips. Increasing concentrations of (-)-isoprenaline produced a biphasic concentration-relaxation response without any difference both during the presence and absence of mucosa. The relaxation fraction produced by low (-)-isoprenaline concentrations was mediated by β2-AR as evidenced by a shift of the concentration-response curve to higher concentrations with ICI 118,551, but not with CGP 20712A and L748,337, and by the absence of this fraction in β2-AR-KO mice. The relaxation response with low sensitivity to (-)-isoprenaline was not affected by any of the β-AR subtype-selective blockers and was the only response detected in detrusor strips from β2-AR-KO mice. Conclusions: In CCh-pre-contracted mouse detrusor, β2-ARs are responsible for the relaxation component with high sensitivity to (-)-isoprenaline as indicated by the conversion of a biphasic into a monophasic CRC with ICI 118,551 or by its absence in β2-AR KO mice. The mucosa does not impair relaxation under these conditions.

2001 ◽  
Vol 280 (5) ◽  
pp. H2380-H2389 ◽  
Author(s):  
Andrea K. Hinschen ◽  
Roselyn B. Rose'Meyer ◽  
John P. Headrick

We tested whether adenosine mediates nitric oxide (NO)-dependent and NO-independent dilation in coronary and aortic smooth muscle and whether age selectively impairs NO-dependent adenosine relaxation. Responses to adenosine and the relatively nonselective analog 5 ′-N-ethylcarboxamidoadenosine (NECA) were studied in coronary vessels and aortas from immature (1–2 mo), mature (3–4 mo), and moderately aged (12–18 mo) Wistar and Sprague-Dawley rats. Adenosine and NECA induced biphasic concentration-dependent coronary vasodilation, with data supporting high-sensitivity (pEC50 = 5.2–5.8) and low-sensitivity (pEC50 = 2.3–2.4) adenosine sites. Although sensitivity to adenosine and NECA was unaltered by age, response magnitude declined significantly. Treatment with 50 μM N G-nitro-l-arginine methyl ester (l-NAME) markedly inhibited the high-sensitivity site, although response magnitude still declined with age. Aortic sensitivity to adenosine declined with age (pEC50 = 4.7 ± 0.2, 3.5 ± 0.2, and 2.9 ± 0.1 in immature, mature, and moderately aged aortas, respectively), and the adenosine receptor transduction maximum also decreased (16.1 ± 0.8, 12.9 ± 0.7, and 9.6 ± 0.7 mN/mm2 in immature, mature, and moderately aged aortas, respectively). l-NAME decreased aortic sensitivity to adenosine in immature and mature tissues but was ineffective in the moderately aged aorta. Data collectively indicate that 1) adenosine mediates NO-dependent and NO-independent coronary and aortic relaxation, 2) maturation and aging reduce NO-independent and NO-dependent adenosine responses, and 3) the age-related decline in aortic response also involves a reduction in the adenosine receptor transduction maximum.


2016 ◽  
Vol 72 (7) ◽  
pp. 849-859
Author(s):  
Ximeng Y. Dow ◽  
Christopher M. Dettmar ◽  
Emma L. DeWalt ◽  
Justin A. Newman ◽  
Alexander R. Dow ◽  
...  

Second harmonic generation correlation spectroscopy (SHG-CS) is demonstrated as a new approach to protein nanocrystal characterization. A novel line-scanning approach was performed to enable autocorrelation analysis without sample damage from the intense incident beam. An analytical model for autocorrelation was developed, which includes a correction for the optical scattering forces arising when focusing intense, infrared beams. SHG-CS was applied to the analysis of BaTiO3nanoparticles ranging from 200 to ∼500 nm and of photosystem I nanocrystals. A size distribution was recovered for each sample and compared with the size histogram measured by scanning electron microscopy (SEM). Good agreement was observed between the two independent measurements. The intrinsic selectivity of the second-order nonlinear optical process provides SHG-CS with the ability to distinguish well ordered nanocrystals from conglomerates and amorphous aggregates. Combining the recovered distribution of particle diameters with the histogram of measured SHG intensities provides the inherent hyperpolarizability per unit volume of the SHG-active nanoparticles. Simulations suggest that the SHG activity per unit volume is likely to exhibit relatively low sensitivity to the subtle distortions within the lattice that contribute to resolution loss in X-ray diffraction, but high sensitivity to the presence of multi-domain crystals.


2003 ◽  
Vol 98 (1) ◽  
pp. 104-113 ◽  
Author(s):  
Ju-Tae Sohn ◽  
Paul A. Murray

Background The authors recently demonstrated that etomidate and ketamine attenuated endothelium-dependent pulmonary vasorelaxation mediated by nitric oxide and Ca -activated K + channels. In the current study, they tested the hypothesis that these intravenous anesthetics inhibit pulmonary vasorelaxation mediated by adenosine triphosphate-sensitive potassium (K + ATP ) channel activation. Methods Endothelium intact and denuded pulmonary arterial rings were suspended in organ chambers for isometric tension recording. The effects of etomidate (5 x 10(-6) and 5 x 10(-5) m) and ketamine (5 x 10(-5) and 10(-4) m) on vasorelaxation responses to lemakalim (K + ATP channel activator), prostacyclin, and papaverine were assessed in phenylephrine-precontracted rings. The effect of cyclooxygenase inhibition with indomethacin was assessed in some protocols. Results Etomidate (5 x 10(-6) m) only inhibited the vasorelaxant response to lemakalim in endothelium intact rings, whereas a higher concentration of etomidate (5 x 10(-5) m) inhibited relaxation in both intact and endothelium-denuded rings. Pretreatment with indomethacin abolished the endothelium-dependent attenuation of lemakalim-induced relaxation caused by etomidate. Ketamine (5 x 10(-5) and 10(-5) m) inhibited the relaxation response to lemakalim to the same extent in both endothelium-intact and -denuded rings, and this effect was not prevented by indomethacin pretreatment. Etomidate and ketamine had no effect on the relaxation responses to prostacyclin or papaverine. Conclusions These results indicate that etomidate, but not ketamine, attenuates the endothelium-dependent component of lemakalim-induced pulmonary vasorelaxation an inhibitory effect on the cyclooxygenase pathway. Both anesthetics inhibit K + ATP -mediated pulmonary vasorelaxation a direct effect on pulmonary vascular smooth muscle.


2021 ◽  
pp. 143-165
Author(s):  
V.G. Maralov ◽  
◽  
V.A. Sitarov ◽  

The relevance of the problem is due to the importance of identifying factors that determine the propensity of students to coercion or nonviolence, creating psychological and pedagogical conditions for the formation of the socionomic sphere of nonviolent competencies for future specialists at universities. The theoretical basis of the study was the position of nonviolence as a daily practice of interaction, by which we understand the ability of a person to choose from a number of possible alternatives that carry the least charge of coercion. The aim of the work was to study the influence of irrational beliefs and sensitivity to a person (interest, empathy, understanding and assistance) on the students’ tendency to coercion, manipulation, non-violence and non-interference in the processes of interaction with people. The hypothesis was tested that the tendency of students to coercion, manipulation, and noninterference will be due to expressed irrational beliefs and low level of sensitivity to a person and the tendency to non-violence will be explained by the absence of irrational beliefs and a high level of sensitivity to a person. The study involved 125 students of pedagogical and psychological faculties of the Moscow Humanitarian and Cherepovets State universities. The authors used questionnaires to identify the positions of interaction among students and sensitivity to a person, as well as a list of irrational beliefs proposed by A. Beck and A. Freeman. It is established that the tendency to both coercion and manipulation are determined by the beliefs of anti-social type and low sensitivity to the person. The tendency to manipulate the narcissistic beliefs, high interest in people and understanding them, at the same time the tendency to non-violence and non-interference are determined by beliefs of avoidant and dependent types with a low level of understanding people. And a tendency to non-interference is determined by beliefs of dependent type with unexpressed orientation on helping. The tendency to nonviolence is determined by the high sensitivity to a person and the absence of irrational beliefs of antisocial, passive-aggressive and narcissistic types. As a result, the conclusion is made about the need to form purposefully the ability to nonviolent interaction among students, which should include the work on awareness and overcoming irrational beliefs and the development of sensitivity to a person. The obtained results can be used in practical work with students on the formation of their nonviolent competencies.


2020 ◽  
Author(s):  
Ganlu Ouyang ◽  
Xibiao Yang ◽  
Xiangbing Deng ◽  
Wenjian Meng ◽  
Yongyang Yu ◽  
...  

Abstract Purpose: To investigate the potential value of magnetic resonance imaging (MRI) in predicting response relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer.Methods: We analyzed MRI of 71 patients underwent TNT from 2015 to 2017 retrospectively. We categorized the response of TNT as CR (complete response) and non-CR, and high, moderate and low sensitivity. Logistic regression analysis was used to identify the best predictors of response. Diagnostic performance was assessed using receiver - operating characteristic curve analysis.Results: Post–ICT (induction chemotherapy) ∆TL (tumor length), post-CRT (concurrent chemoradiotherapy) ∆LNN (the numbers of lymph node metastases), post–CCT (consolidation chemotherapy) ∆SDWI (maximum cross-sectional area of tumor on diffusion-weighted imaging), post-CCT ADCT (the mean apparent diffusion coefficient values of tumor) and post-CCT ∆LNV (volume of lymph node) were the best CR predictors. Post-CRT EMVI (extramural vascular invasion) and post-CCT ∆ST2 (S on T2-weight) were the best significant factors for high sensitivity. Conclusions: Post-ICT ∆TL and post-CRT EMVI may an early predictor of CR and high sensitivity to TNT, respectively. The grouping scheme of CR and non–CR was more suitable for predicting response by MRI parameters than high, moderate and low sensitivity.Trial registration: retrospectively registered


2018 ◽  
Author(s):  
Grace E. Shupe ◽  
Arran Wilson ◽  
Curtis R. Luckett

AbstractMastication behavior is a notable source of interindividual variation in texture perception and could be linked to oral sensitivity. As oral sensitivity declines so does the amount of tactile feedback relayed to the brain, resulting in less effective manipulation or food and a reduced ability to discriminate differences. To address these hypotheses, we measured masticatory behavior and related this to texture discrimination and oral sensitivity. The study was performed on 41 participants in two groups, with high (n = 20) or low (n=21) sensitivity. Oral sensitivity was measured using a battery of tests that included: oral stereognosis, lingual tactile acuity, and bite force sensitivity. Sensitivity to texture changes was measured using a series of triangle tests with confectionaries of different hardness, with masticatory patterns and behaviors being video recorded and analyzed using jaw tracking software. Overall, there was no significant difference between high and low sensitivity participants and their ability to distinguish texture changes. But, there were significantly different trends found between the groups based on their masticatory behaviors including chewing pattern and overall number of chews. But, it was found that multiple masticatory behaviors were being modulated by oral sensitivity, including overall chewing cycles used (p < 0.0001). More, specifically those in the high sensitivity group used more stochastic chewing movements, while those in the low sensitivity group were found to use crescent-shaped chewing cycles. It was also noted that in the high sensitivity group the jaw moved further distances (p < 0.0001) in all phases and moved at a higher velocity when opening (p < 0.0001) but not when closing, when compared to the low sensitivity group. These results help bolster evidence that mastication and oral sensitivity are related.


BJPsych Open ◽  
2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Andrea C. King ◽  
Dingcai Cao ◽  
Harriet deWit ◽  
Sean J. O'Connor ◽  
Deborah S. Hasin

Summary Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol (‘low-level response’) imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.


1985 ◽  
Vol 112 ◽  
pp. 397-403
Author(s):  
Michael J. Klein ◽  
Samuel Gulkis

NASA's microwave observing program for SETI is presented. This strategy is composed of a high sensitivity, narrow frequency coverage, Target Search and a low sensitivity, broad frequency coverage, Sky Survey. The complementary nature of this dual mode search strategy is discussed. An overview is given of ongoing work in the development of the search strategy for the Sky Survey.


Author(s):  
Yutaka Kondo ◽  
Toru Hifumi ◽  
Junya Shimazaki ◽  
Yasutaka Oda ◽  
Shin-ichiro Shiraishi ◽  
...  

Background: This study aims to compare the Bouchama heatstroke (B-HS) and Japanese Association for Acute Medicine heatstroke (JAAM-HS) criteria with regard to the diagnosis and prediction of mortality and neurological status of heatstroke patients. Methods: This multicenter observational study recruited eligible patients from the emergency departments of 110 major hospitals in Japan from 1 July to 30 September, 2014. Results: A total of 317 patients (median age, 65 years; interquartile range, 39–80 years) were included and divided into the B-HS, JAAM-HS, and non-HS groups, with each group consisting of 97, 302, and 15 patients, respectively. The JAAM-HS (1.0; 95% confidence interval [CI], 0.87–1.0) and B-HS (0.29; 95% CI, 0.14–0.49) criteria showed high and low sensitivity to mortality, respectively. Similarly, the JAAM-HS (1.0; 95% CI, 0.93–1.0) and B-HS (0.35; 95% CI, 0.23–0.49) criteria showed high and low sensitivity to poor neurological status, respectively. Meanwhile, the sequential organ failure assessment (SOFA) scores demonstrated good accuracy in predicting mortality among heat-related illness (HRI) patients. However, both JAAM-HS and B-HS criteria could not predict in-hospital mortality. The AUC of the SOFA score for mortality was 0.83 (day 3) among the HRI patients. The patients’ neurological status was difficult to predict using the JAAM-HS and B-HS criteria. Concurrently, the total bilirubin level could relatively predict the central nervous system function at discharge. Conclusions: The JAAM-HS criteria showed high sensitivity to mortality and could include all HRI patients who died. The JAAM-HS criterion was considered a useful tool for judgement of admission at ED. Further investigations are necessary to determine the accuracy of both B-HS and JAAM-HS criteria in predicting mortality and neurological status at discharge.


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