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Strain represents the quantification of regional tissue deformation within a given area. Myocardial strain has demonstrated considerable utility as an indicator for the assessment of cardiac function. Notably, it exhibits greater sensitivity in detecting subtle myocardial abnormalities compared to conventional cardiac function indices, like left ventricle ejection fraction (LVEF). Nonetheless, the estimation of strain poses considerable challenges due to the necessity for precise tracking of myocardial motion throughout the complete cardiac cycle. This study introduces a novel deep learning-based pipeline, designed to automatically and accurately estimate myocardial strain from three-dimensional (3D) cine-MR images. Consequently, our investigation presents a comprehensive pipeline for the precise quantification of local and global myocardial strain. This pipeline incorporates a supervised Convolutional Neural Network (CNN) for accurate segmentation of the cardiac muscle and an unsupervised CNN for robust left ventricle motion tracking, enabling the estimation of strain in both artificial phantoms and real cine-MR images. Our investigation involved a comprehensive comparison of our findings with those obtained from two commonly utilized commercial software in this field. This analysis encompassed the examination of both intra- and inter-user variability. The proposed pipeline exhibited demonstrable reliability and reduced divergence levels when compared to alternative systems. Additionally, our approach is entirely independent of previous user data, effectively eliminating any potential user bias that could influence the strain analyses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Catharine De Vita Graves reports financial support was provided by Canon Medical Systems Corporation. Marina F. S. Rebelo reports financial support was provided by Canon Medical Systems Corporation. Ramon A. Moreno reports financial support was provided by Canon Medical Systems Corporation. Cesar H. Nomura reports financial support was provided by Canon Medical Systems Corporation. Marco A. Gutierrez reports financial support was provided by Canon Medical Systems Corporation. Catharine De Vita Graves has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Marina F. S. Rebelo has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Ramon A. Moreno has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Cesar H. Nomura has patent #BR512022001946-9 licensed to INPI - Instituto Nacional da Propriedade Industrial. Marco A. Gutierrez has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 μM) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 μM) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA 2 6.09) and L-NAME pre-treated endothelium-intact (pA 2 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 μM). In the thromboxane A 2 mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 μM) and the dopamine D 2 -receptor antagonist haloperidol (1 nM-1 μM) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D 2 -like receptor antagonist., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The role of endothelium in the electrical-field stimulation (EFS)-induced contractions of Chelonoidis carbonaria aorta was investigated. Contractions were evaluated in the presence and absence of L-NAME (100 μM), tetrodotoxin (1 μM), phentolamine (10 and 100 μM), phenoxybenzamine (1 and 10 μM), prazosin (100 μM), idazoxan (100 μM), atropine (10 μM), D-tubocurarine (10 μM) or indomethacin (10 μM). EFS-induced contraction was also carried out in endothelium-denuded rings. EFS-induced contraction was investigated by the sandwich assay. Concentration curves to endothelin-1 (0.1-100 nM) and U46619 (0.001-100 μM) were also constructed to calculate both Emax and EC 50 . EFS at 16 Hz contracted Chelonoidis aorta, which was almost abolished by the endothelium removal. The addition of L-NAME increased the EFS response (2.0 ± 0.4 and 8.3 ± 1.9 mN). In L-NAME treated aortic rings, tetrodotoxin did not change the EFS-response (5.1 ± 1.8 and 4.9 ± 1.7 mN). Indomethacin, atropine and d-tubucurarine also did not affect the EFS-response. Phentolamine at 10 μM did not change the EFS-induced contraction; however, at 100 μM, reduced it (3.9 ± 1 and 1.9 ± 0.3 mN). Prazosin and idazoxan did not change EFS-induced contractions. Phenoxybenzamine at 1 μM reduced by 76% (9.6 ± 3.4 and 2.3 ± 0.8 mN) and at 10 μM by 90% the EFS response. Immunohistochemistry identified tyrosine hydroxylase in the endothelium and brain, whereas S100 protein was found only in brain. In conclusion, endothelium modulates EFS-induced contractions in Chelonoidis aortic rings and this modulation may be due to endothelium-derived catecholamines, possibly dopamine., Competing Interests: Declaration of competing interest We declare that the content of this manuscript has not been published or submitted for publication elsewhere. We also declare that this manuscript has no conflicts of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this study the nitric oxide (NO)-soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) pathway was characterized in tortoise Chelonoidis carbonaria aorta. Concentration response curves (CCR) to ATP, ADP, AMP, adenosine and histamine were performed in the presence and absence of L-NAME in aorta pre-contracted with ACh (3 μM). CCR to SNP, BAY 41-2272 (sGC stimulator), BAY 60-2770 (sGC activator) and tadalafil (PDE-5 inhibitor) were constructed in the presence and absence of ODQ (10 μM). ATP (pEC 50 6.1 ± 0.1), ADP (pEC 50 6.0 ± 0.2), AMP (pEC 50 6.8 ± 0.1) and histamine (pEC 50 6.8 ± 0.12) relaxed Chelonoidis aorta and the addition of L-NAME reduced their efficacy (p < .05). Adenosine effects (pEC 50 6.6 ± 0.1) were not changed in the presence of L-NAME. SNP (pEC 50 7.5 ± 0.7; Emax 102.2 ± 2.5%), BAY 41-2272 (pEC 50 7.3 ± 0.2; Emax 130.3 ± 10.2%), BAY 60-2770 (pEC 50 11.4 ± 0.1; Emax 130.3 ± 6.5%) and tadalafil (pEC 50 6.7 ± 0.3; Emax 121.3 ± 15.3%) relaxed Chelonoidis aorta. The addition of ODQ reduced the SNP and tadalafil maximum response (p < .05) and promoted 63 fold right shift on BAY 41-2272 curve. In contrast, no alteration was observed on BAY 60-2770 response. Transcriptomic analysis for eNOS and sGC were found in aorta and brain libraries with high homology when compared with human transcripts. The NO-sGC-PDE-5 is functionally present in Chelonoidis aorta with a functional and genomic similarity to mammalian vessels. Unlike most of mammalian vessels, ACh did not cause endothelium-dependent relaxation in Chelonoidis carbonaria aortic rings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The combination of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg is a highly effective, monthly injectable contraceptive. For the first time, this study presents the development and validation of a sensitive method for estradiol cypionate analysis in human plasma by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Aliquots (500 μL) of plasma were extracted with ethyl ether (100%) and derivatized with dansyl chloride. Its separation was performed on a Jones Chromatography Genesis C8 column and the quantification was performed with a mass spectrometer equipped with an electrospray interface operating in negative ion mode. The run time was 6 min and the calibration curve was linear over the range of 0.005-0.15 ng/mL. The method was applied to evaluate the pharmacokinetics of estradiol cypionate in plasma collected up to 1008 h (42 days) after a single intramuscular administration of 25 mg/mL medroxyprogesterone acetate +5 mg/mL estradiol cypionate to healthy female volunteers (n = 12). The estradiol cypionate maximum plasma concentration (C max ) was 0.14 ± 0.08 ng/mL reached at 16.83 ± 21.07 h and the area under the plasma concentration versus time curve (AUC 0-last ) was 14.07 ± 6.32 ng.h/mL. Elimination half-life (t ½ ), apparent volume of distribution (Vd/F), apparent clearance (CL/F) and mean residence time (MRT) were 89.65 ± 76.04 h, 28038 ± 9636 L, 49.02 ± 10.62 L/h and 576.05 ± 238.32 h, respectively, showing that the estradiol cypionate release from the administration site was prolonged and there was no drug accumulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To examine the effects of Tityus serrulatus scorpion venom (TSV) on human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally observed in scorpion envenomation, mostly in children., Methods: HCC strips were suspended in a cascade system and superfused with aerated and warmed Krebs' solution at 5 mL/min. Noradrenaline (3 micromol/L) was infused to induce a submaximal contraction of the HCC strips. The release of cyclooxygenase products was prevented by infusing indomethacin (6 micromol/L)., Results: N(omega)-nitro-L-arginine methyl ester (10 micromol/L; n = 10) increased the tone of the preparations and significantly reduced (P <0.01) the acetylcholine (ACh) and TSV-induced relaxations. Subsequent infusion of L-arginine (300 micromol/L) partially reversed the increased tone and significantly restored the relaxations induced by TSV and ACh (P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 micromol/L; n = 8) markedly reduced (P <0.01) the relaxations induced by TSV, ACh, glyceryl trinitrate, and bradykinin. 7-Nitroindazole (10 micromol/L; n = 8) inhibited the relaxations induced by TSV by 84% (P <0.01) and also caused small, but significant, reductions in the ACh and bradykinin-induced HCC relaxations (P <0.05). Atropine (1 micromol/L; n = 6) abolished the relaxations evoked by ACh (P <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 micromol/L; n = 6) abolished the relaxations induced by TSV (P <0.01) and also reversed the established TSV-induced relaxation (n = 4)., Conclusions: Our results indicate that TSV relaxes HCC through the release of nitric oxide from nonadrenergic, noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for the TSV-induced relaxations might be useful for a better understanding of the development of priapism in cases of scorpion envenomation.