Normalization of organ bath contraction data for tissue specimen size: does one approach fit all?

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

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Effect of Testing Method Type and Specimen Size on Mode I Fracture Toughness of Kimachi Sandstone

Journal of MMIJ ◽

10.2473/journalofmmij.135.33 ◽

2019 ◽

Vol 135 (5) ◽

pp. 33-41 ◽

Cited By ~ 1

Author(s):

Minami KATAOKA ◽

Yuzo OBARA ◽

Leona VAVRO ◽

Kamil SOUCEK ◽

Sang-Ho CHO ◽

...

Keyword(s):

Fracture Toughness ◽

Specimen Size ◽

Mode I ◽

Mode I Fracture ◽

Mode I Fracture Toughness ◽

Testing Method

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Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90667.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. R1486-R1493 ◽

Cited By ~ 40

Author(s):

Tim Lahm ◽

Paul R. Crisostomo ◽

Troy A. Markel ◽

Meijing Wang ◽

Yue Wang ◽

...

Keyword(s):

Nitric Oxide ◽

Estrogen Receptor ◽

Pulmonary Artery ◽

Hypoxic Pulmonary Vasoconstriction ◽

Organ Bath ◽

Sprague Dawley ◽

Response Curves ◽

Vascular Effects ◽

M 10 ◽

Dependent Mechanism

Both endogenous and exogenous estrogen decrease pulmonary artery (PA) vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)-α or ER-β, and whether the contribution of ERs is stimulus-dependent, remains unknown. We hypothesized that administration of the selective ER-α agonist propylpyrazole triol (PPT) and/or the selective ER-β agonist diarylpropiolnitrile (DPN) rapidly decreases PA vasoconstriction induced by pharmacologic and hypoxic stimuli via a nitric oxide (NO)-dependent mechanism. PA rings ( n = 3–10/group) from adult male Sprague-Dawley rats were suspended in physiologic organ baths. Force displacement was measured. Vasoconstrictor responses to phenylephrine (10−8M − 10−5M) and hypoxia (Po2 35–45 mmHg) were determined. Endothelium-dependent and -independent vasorelaxation were measured by generating dose-response curves to acetylcholine (10−8M − 10−4M) and sodium nitroprusside (10−9M − 10−5M). PPT or DPN (10−9M − 5 × 10−5M) were added to the organ bath in the presence and absence of the NO-synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) (10−4M). Selective ER-α activation (PPT, 5 × 10−5M) rapidly (<20 min) decreased phenylephrine-induced vasoconstriction. This effect, as well as PPT's effects on endothelium-dependent vasorelaxation, were neutralized by l-NAME. In contrast, selective ER-β activation (DPN, 5 × 10−5M) rapidly decreased phase II of hypoxic pulmonary vasoconstriction (HPV). l-NAME eliminated this phenomenon. Lower PPT or DPN concentrations were less effective. We conclude that both ER-α and ER-β decrease PA vasoconstriction. The immediate onset of effect suggests a nongenomic mechanism. The contribution of specific ERs appears to be stimulus specific, with ER-α primarily modulating phenylephrine-induced vasoconstriction, and ER-β inhibiting HPV. NO inhibition eliminates these effects, suggesting a central role for NO in mediating the pulmonary vascular effects of both ER-α and ER-β.

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Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽

10.3390/biomedicines9060676 ◽

2021 ◽

Vol 9 (6) ◽

pp. 676

Author(s):

Kunanya Masodsai ◽

Yi-Yuan Lin ◽

Sih-Yin Lin ◽

Chia-Ting Su ◽

Shin-Da Lee ◽

...

Keyword(s):

Growth Factor ◽

Endothelial Dysfunction ◽

Spontaneously Hypertensive Rats ◽

No Production ◽

Organ Bath ◽

Insulin Like Growth Factor ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Nos Inhibitors ◽

Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

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OP0150 WHAT IS THE ROLE OF TEMPORAL ARTERY BIOPSY IN GIANT CELL ARTERITIS FAST-TRACK PATHWAYS WHEN TEMPORAL ARTERY ULTRASOUND IS NEGATIVE?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6534 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 95.3-95

Author(s):

A. Sachdev ◽

S. Dubey ◽

C. Tiivas ◽

M. George ◽

P. Mehta

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Sensitivity And Specificity ◽

Fast Track ◽

Temporal Artery ◽

Clinical Findings ◽

Specimen Size ◽

Temporal Artery Biopsy ◽

Duration Of Treatment ◽

Relevant Role

Background:A number of centres are now running fast track pathways for diagnosis and management of Giant cell arteritis with ultrasound as the first port of call for diagnosis1. Temporal artery biopsies (TABs) have become the second line of investigation, and it is unclear how useful TAB is in this setting.Objectives:This study looked at accuracy of Temporal artery biopsy (TAB) in patients with suspected Giant Cell arteritis (GCA) with negative/inconclusive ultrasound (U/S) and how duration of treatment on steroids prior to these investigations and arterial specimen size affected it.Methods:Prospective study of all patients with suspected GCA referred for TAB when U/S was negative or inconclusive, as part of the local fast-track pathway (Coventry). Database included clinical findings, serological work up, U/S and TAB results and treatment. Sensitivity and specificity of U/S and TAB was calculated and compared based on duration of treatment with steroids.Results:One hundred and nine patients were referred for TAB via Coventry fast-track-pathway. The sensitivity of U/S in this cohort of patients was 9.08% and specificity was 93.33%. After 3 days of steroid this was 0% and 100% respectively. For TAB when done within 10 days of starting steroids, this was 65% and 87.5% respectively. After 20 days of steroids this was 0 % and 100%. The sensitivity and specificity was 20% and 85% when arterial specimen size was 11-15mm and 47% and 100% when specimen size was 16 mm or more. Sensitivity and specificity of U/S of 644 suspected GCA patients was 48% and 98%.Conclusion:Our study demonstrates that TAB plays a relevant role in GCA fast-track-pathways, when U/S is negative/inconclusive. TAB was more sensitive than U/S in this cohort of patients, but overall sensitivity of U/S was higher when calculated for all patients suspected with GCA. Both remain useful tests if performed early. TAB specimen size should ideally be 16mm or more and done within 10 days of starting steroids.References:[1]Jonathan Pinnell, Carl Tiivas, Kaushik Chaudhuri, Purnima Mehta, Shirish Dubey, O38 The diagnostic performance of ultrasound Doppler in a fast-track pathway for giant cell arteritis,Rheumatology, Volume 58, Issue Supplement_3, April 2019, kez105.036,https://doi.org/10.1093/rheumatology/kez105.036Disclosure of Interests:None declared

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Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

Gynecologic and Obstetric Investigation ◽

10.1159/000513718 ◽

2021 ◽

pp. 1-8

Author(s):

Beata Modzelewska ◽

Marcin Jóźwik ◽

Tomasz Kleszczewski ◽

Stanisław Sulkowski ◽

Maciej Jóźwik

Keyword(s):

Ovarian Cancer ◽

Cervical Cancer ◽

Reference Group ◽

Ex Vivo ◽

Contractile Activity ◽

Organ Bath ◽

Human Uterus ◽

Uterine Contractility ◽

Beta Adrenoceptor ◽

Gynecological Malignancies

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

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The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22157774 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7774

Author(s):

Sevil Korkmaz-Icöz ◽

Cenk Kocer ◽

Alex A. Sayour ◽

Patricia Kraft ◽

Mona I. Benker ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Reperfusion Injury ◽

Vascular Function ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Artery Bypass ◽

Diabetic Rats ◽

Organ Bath ◽

Sodium Glucose Cotransporter

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.

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Experimental data on strength properties of mussel shell concretes and specimen size effect

Data in Brief ◽

10.1016/j.dib.2021.106954 ◽

2021 ◽

Vol 35 ◽

pp. 106954

Author(s):

Costas A. Anagnostopoulos ◽

Denis Cabja ◽

Chrysi A. Papadimitriou

Keyword(s):

Experimental Data ◽

Size Effect ◽

Strength Properties ◽

Specimen Size ◽

Mussel Shell

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From macro- to micro-experiments: Specimen-size independent identification of plasticity and fracture properties

International Journal of Mechanical Sciences ◽

10.1016/j.ijmecsci.2021.106389 ◽

2021 ◽

Vol 199 ◽

pp. 106389

Author(s):

Maysam B. Gorji ◽

Jevan Furmanski ◽

Dirk Mohr

Keyword(s):

Specimen Size ◽

Fracture Properties

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Fracture and Size Effect of PFRC Specimens Simulated by Using a Trilinear Softening Diagram: A Predictive Approach

Materials ◽

10.3390/ma14143795 ◽

2021 ◽

Vol 14 (14) ◽

pp. 3795

Author(s):

Fernando Suárez ◽

Jaime C. Gálvez ◽

Marcos G. Alberti ◽

Alejandro Enfedaque

Keyword(s):

Reinforced Concrete ◽

Size Effect ◽

A Priori ◽

Plain Concrete ◽

Specimen Size ◽

Bending Test ◽

Orientation Factor ◽

Fibre Reinforced Concrete ◽

Softening Function ◽

Three Point Bending

The size effect on plain concrete specimens is well known and can be correctly captured when performing numerical simulations by using a well characterised softening function. Nevertheless, in the case of polyolefin-fibre-reinforced concrete (PFRC), this is not directly applicable, since using only diagram cannot capture the material behaviour on elements with different sizes due to dependence of the orientation factor of the fibres with the size of the specimen. In previous works, the use of a trilinear softening diagram proved to be very convenient for reproducing fracture of polyolefin-fibre-reinforced concrete elements, but only if it is previously adapted for each specimen size. In this work, a predictive methodology is used to reproduce fracture of polyolefin-fibre-reinforced concrete specimens of different sizes under three-point bending. Fracture is reproduced by means of a well-known embedded cohesive model, with a trilinear softening function that is defined specifically for each specimen size. The fundamental points of these softening functions are defined a priori by using empirical expressions proposed in past works, based on an extensive experimental background. Therefore, the numerical results are obtained in a predictive manner and then compared with a previous experimental campaign in which PFRC notched specimens of different sizes were tested with a three-point bending test setup, showing that this approach properly captures the size effect, although some values of the fundamental points in the trilinear diagram could be defined more accurately.

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