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https://www.readbyqxmd.com/read/30090996/second-generation-cryoballoon-ablation-for-recurrent-atrial-fibrillation-after-an-index-cryoballoon-procedure-a-staged-strategy-with-variable-balloon-size
#1
Sjoerd W Westra, Stijn P G van Vugt, Sümeyye Sezer, Reinder Evertz, Martin E Hemels, Rypko J Beukema, Carlo de Asmundis, Marc A Brouwer, Gian-Battista Chierchia
PURPOSE: Currently, information on the optimal approach of redo procedures for paroxysmal atrial fibrillation (PAF) is limited. Radiofrequency ablation is the preferred technique, with reported success rates of 50-70% at 1-2 years, whereas only few reports exist on redo cryoballoon (CB) ablations. We describe outcomes on a systematic approach of repeat procedures with a second-generation cryoballoon (CB-2) after a successful index CB ablation. METHODS: Cohort study of 40 consecutive patients with recurrent PAF (55% male), median CHA2 DS2 -VASc score 1 (IQR 0-3)...
August 8, 2018: Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing
https://www.readbyqxmd.com/read/30055149/emerging-strategies-targeting-cb-2-cannabinoid-receptor-biased-agonism-and-allosterism
#2
REVIEW
Paula Morales, Pilar Goya, Nadine Jagerovic
During these last years, the CB2 cannabinoid receptor has emerged as a potential anti-inflammatory target in diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, ischemic stroke, autoimmune diseases, osteoporosis, and cancer. However, the development of clinically useful CB2 agonists reveals to be very challenging. Allosterism and biased-signaling mechanisms at CB2 receptor may offer new avenues for the development of improved CB2 receptor-targeted therapies. Although there has been some exploration of CB1 receptor activation by new CB1 allosteric or biased-signaling ligands, the CB2 receptor is still at initial stages in this domain...
July 25, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30033591/vce-004-3-a-cannabidiol-aminoquinone-derivative-prevents-bleomycin-induced-skin-fibrosis-and-inflammation-trough-ppar%C3%AE-and-cb-2-dependent-pathways
#3
Carmen Del Rio, Irene Cantarero, Belén Palomares, María Gómez-Cañas, Javier Fernández-Ruiz, Carolina Pavicic, Adela García-Martín, M Luz Bellido, Rafaela Ortega-Castro, Carlos Pérez-Sánchez, Chary López-Pedrera, Giovanni Appendino, Marco A Calzado, Eduardo Muñoz
BACKGROUND AND PURPOSE: The endocannabinoid system (ECS) as well as PPARγ are relevant targets for the development of novel compounds against fibrotic diseases such as Systemic Sclerosis (SSc), also called Scleroderma. The aim of this study was to characterize VCE-004.3, a novel cannabidiol derivative, and to study it anti-inflammatory and anti-fibrotic activities. EXPERIMENTAL APPROACH: CB1 , CB2 and PPARγbinding and functional activities were studied in vitro and in silico...
July 22, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29990428/identification-of-the-first-synthetic-allosteric-modulator-of-the-cb-2-receptors-and-evidence-of-its-efficacy-for-neuropathic-pain-relief
#4
Francesca Gado, Lorenzo Di Cesare Mannelli, Elena Lucarini, Simone Bertini, Elena Cappelli, Maria Digiacomo, Lesley A Stevenson, Marco Macchia, Tiziano Tuccinardi, Carla Ghelardini, Roger G Pertwee, Clementina Manera
The direct activation of cannabinoid receptors (CBRs) results in several beneficial effects; therefore several CBRs ligands have been synthesized and tested in vitro and in vivo. However, none of them reached an advanced phase of clinical development due mainly to side effects on the CNS. Medicinal chemistry approaches are now engaged to develop allosteric modulators that might offer a novel therapeutic approach to achieve potential therapeutic benefits avoiding inherent side effects of orthosteric ligands...
July 23, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29977202/cannabigerol-action-at-cannabinoid-cb-1-and-cb-2-receptors-and-at-cb-1-cb-2-heteroreceptor-complexes
#5
Gemma Navarro, Katia Varani, Irene Reyes-Resina, Verónica Sánchez de Medina, Rafael Rivas-Santisteban, Carolina Sánchez-Carnerero Callado, Fabrizio Vincenzi, Salvatore Casano, Carlos Ferreiro-Vera, Enric I Canela, Pier Andrea Borea, Xavier Nadal, Rafael Franco
Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1 R) and CB2 (CB2 R) receptors and the effects of the compound on agonist activation of those receptors and of CB1 -CB2 heteroreceptor complexes. Using [3 H]-CP-55940, CBG competed with low micromolar K i values the binding to CB1 R and CB2 R...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29967455/cb-2-receptor-antibody-signal-specificity-correlations-with-the-use-of-partial-cb-2-knockout-mice-and-anti-rat-cb-2-receptor-antibodies
#6
Hai-Ying Zhang, Hui Shen, Chloe J Jordan, Qing-Rong Liu, Eliot L Gardner, Antonello Bonci, Zheng-Xiong Xi
Cannabinoid CB1 receptors are highly expressed in the brain and functionally modulate presynaptic neurotransmitter release, while cannabinoid CB2 receptors (CB2 Rs) were initially identified in the spleen and regarded as peripheral cannabinoid receptors. Recently, growing evidence indicates the presence of functional CB2 Rs in the brain. However, this finding is disputed because of the specificity of CB2 R antibody signals. We used two strains of currently available partial CB2 -knockout (CB2 -KO) mice as controls, four anti-rat or anti-mouse CB2 R antibodies, and mRNA quantification to further address this issue...
July 2, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29906493/the-tamoxifen-derivative-ridaifen-b-is-a-high-affinity-selective-cb-2-receptor-inverse-agonist-exhibiting-anti-inflammatory-and-anti-osteoclastogenic-effects
#7
Lirit N Franks, Benjamin M Ford, Toshifumi Fujiwara, Haibo Zhao, Paul L Prather
Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors...
June 12, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29870711/molecular-and-functional-interaction-between-gpr18-and-cannabinoid-cb-2-g-protein-coupled-receptors-relevance-in-neurodegenerative-diseases
#8
Irene Reyes-Resina, Gemma Navarro, David Aguinaga, Enric I Canela, Clara T Schoeder, Michał Załuski, Katarzyna Kieć-Kononowicz, Carlos A Saura, Christa E Müller, Rafael Franco
GPR18, still considered an orphan receptor, may respond to endocannabinoids, whose canonical receptors are CB1 and CB2 . GPR18 and CB2 receptors share a role in peripheral immune response regulation and are co-expressed in microglia, which are immunocompetent cells in the central nervous system (CNS). We aimed at identifying heteroreceptor complexes formed by GPR18 and CB1 R or CB2 R in resting and activated microglia. Receptor-receptor interaction was assessed using energy-transfer approaches, and receptor function by determining cAMP levels and ERK1/2 phosphorylation in heterologous cells and primary cultures of microglia...
June 2, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29793509/cannabinoid-cb-2-receptors-in-the-mouse-brain-relevance-for-alzheimer-s-disease
#9
Alicia López, Noelia Aparicio, M Ruth Pazos, M Teresa Grande, M Asunción Barreda-Manso, Irene Benito-Cuesta, Carmen Vázquez, Mario Amores, Gonzalo Ruiz-Pérez, Elena García-García, Margaret Beatka, Rosa M Tolón, Bonnie N Dittel, Cecilia J Hillard, Julián Romero
BACKGROUND: Because of their low levels of expression and the inadequacy of current research tools, CB2 cannabinoid receptors (CB2 R) have been difficult to study, particularly in the brain. This receptor is especially relevant in the context of neuroinflammation, so novel tools are needed to unveil its pathophysiological role(s). METHODS: We have generated a transgenic mouse model in which the expression of enhanced green fluorescent protein (EGFP) is under the control of the cnr2 gene promoter through the insertion of an Internal Ribosomal Entry Site followed by the EGFP coding region immediately 3' of the cnr2 gene and crossed these mice with mice expressing five familial Alzheimer's disease (AD) mutations (5xFAD)...
May 24, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29792186/involvement-of-the-cb-2-cannabinoid-receptor-in-cell-growth-inhibition-and-g0-g1-cell-cycle-arrest-via-the-cannabinoid-agonist-win-55-212-2-in-renal-cell-carcinoma
#10
Mohammed I Khan, Anna A Sobocińska, Klaudia K Brodaczewska, Katarzyna Zielniok, Malgorzata Gajewska, Claudine Kieda, Anna M Czarnecka, Cezary Szczylik
BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2 ), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29791076/effects-of-endurance-training-on-hippocampus-dj-1-cannabinoid-receptor-type-2-and-blood-glucose-concentration-in-diabetic-rats
#11
Mohammad Kurd, Vahid Valipour Dehnou, Seyed A Tavakoli, Daniel E Gahreman
AIMS/INTRODUCTION: To investigate the effect of endurance training on hippocampus DJ-1 and cannabinoid receptor type 2 (CB2 ) protein and blood glucose concentration in diabetic rats. MATERIALS AND METHODS: A total of 32 rats were randomly divided into diabetic (D), diabetic and exercise (DE), exercise (E) and control (C) groups. The endurance training was carried out five times per week for 6 weeks. The hippocampus DJ-1 and CB2 were measured using an enzyme-linked immunosorbent assay method...
May 23, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29574689/targeting-glial-cannabinoid-cb-2-receptors-to-delay-the-progression-of-the-pathological-phenotype-in-tdp-43-a315t-transgenic-mice-a-model-of-amyotrophic-lateral-sclerosis
#12
Francisco Espejo-Porras, Laura García-Toscano, Carmen Rodríguez-Cueto, Irene Santos-García, Eva de Lago, Javier Fernandez-Ruiz
BACKGROUND AND PURPOSE: Cannabinoid CB2 receptors are up-regulated in reactive microglia in the spinal cord of TDP-43 (A315T) transgenic mice, an experimental model of amyotrophic lateral sclerosis. To determine whether this up-regulation can be exploited pharmacologically, we investigated the effects of different treatments that affect CB2 receptor function. EXPERIMENTAL APPROACH: We treated TDP-43 (A315T) transgenic mice with the non-selective agonist WIN55,212-2, alone or combined with selective CB1 or CB2 antagonists, as well as with the selective CB2 agonist HU-308, and evaluated their effects on the pathological phenotype...
March 25, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29574067/structure-kinetic-relationship-studies-of-cannabinoid-cb-2-receptor-agonists-reveal-substituent-specific-lipophilic-effects-on-residence-time
#13
Marjolein Soethoudt, Mark W H Hoorens, Ward Doelman, Andrea Martella, Mario van der Stelt, Laura H Heitman
A decade ago, the drug-target residence time model has been (re-)introduced, which describes the importance of binding kinetics of ligands on their protein targets. Since then, it has been applied successfully for multiple protein targets, including GPCRs, for the development of lead compounds with slow dissociation kinetics (i.e. long target residence time) to increase in vivo efficacy or with short residence time to prevent on-target associated side effects. To date, this model has not been applied in the design and pharmacological evaluation of novel selective ligands for the cannabinoid CB2 receptor (CB2 R), a GPCR with therapeutic potential in the treatment of tissue injury and inflammatory diseases...
June 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29450258/the-cannabinoids-%C3%AE-8-thc-cbd-and-hu-308-act-via-distinct-receptors-to-reduce-corneal-pain-and-inflammation
#14
Dinesh Thapa, Elizabeth A Cairns, Anna-Maria Szczesniak, James T Toguri, Meggie D Caldwell, Melanie E M Kelly
Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1 R) and cannabinoid 2 (CB2 R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia (increased pain response) was generated using chemical cauterization of the corneal epithelium in wild-type (WT) and CB2 R knockout (CB2 R-/- ) mice...
2018: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29276070/a-piecewise-mass-spring-damper-model-of-the-human-breast
#15
Yiqing Cai, Lihua Chen, Winnie Yu, Jie Zhou, Frances Wan, Minyoung Suh, Daniel Hung-Kay Chow
Previous models to predict breast movement whilst performing physical activities have, erroneously, assumed uniform elasticity within the breast. Consequently, the predicted displacements have not yet been satisfactorily validated. In this study, real time motion capture of the natural vibrations of a breast that followed, after raising and allowing it to fall freely, revealed an obvious difference in the vibration characteristics above and below the static equilibrium position. This implied that the elastic and viscous damping properties of a breast could vary under extension or compression...
January 23, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29235702/in-vitro-evaluation-of-resilient-liner-after-brushing-with-conventional-and-experimental-ricinus-communis-based-dentifrices
#16
Maurício Malheiros Badaró, Talita Pereira Prates, Vanessa Maria Fagundes Leite-Fernandes, Viviane de Cássia Oliveira, Helena de Freitas Oliveira Paranhos, Cláudia Helena Silva-Lovato
PURPOSE: To evaluate the effect of experimental (Ricinus communis) and commercial dentifrices used for denture cleaning on abrasiveness (gravimetric method; roughness), hardness, and color stability of a resilient relining material. MATERIALS AND METHODS: Sixty circular (15 × 3 mm) specimens were distributed into four groups: C (control; brushing with water); CO (brushing with Colgate - for natural teeth); CB (brushing with Corega Brite - for complete dentures); RC (brushing with experimental dentifrice)...
December 13, 2017: Journal of Prosthodontics: Official Journal of the American College of Prosthodontists
https://www.readbyqxmd.com/read/29163400/prevalence-and-antibiotic-resistance-of-non-typhoidal-salmonella-isolated-from-raw-chicken-carcasses-of-commercial-broilers-and-spent-hens-in-tai-an-china
#17
Song Li, Yufa Zhou, Zengmin Miao
The present study was aimed to determine the prevalence and characteristics of Salmonella isolated from meat samples of commercial broilers (CB) and spent hens (SH). Between March and June 2016, 200 retail raw chicken carcasses (100 from CB and 100 from SH) were obtained from local supermarkets in Tai'an city of China, and Salmonella isolates were then analyzed for antibiotic resistance, serotype, β-lactamase genes, and the presence of class 1 integron. Forty Salmonella strains were obtained in this study (CB: 21/100, 21%; SH: 19/100, 19%)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29156899/modulating-the-endocannabinoid-pathway-as-treatment-for-peripheral-neuropathic-pain-a-selected-review-of-preclinical-studies
#18
Shannon O'Hearn, Patrick Diaz, Bo Angela Wan, Carlo DeAngelis, Nicholas Lao, Leila Malek, Edward Chow, Alexia Blake
Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon...
December 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/28982142/optimal-timing-of-blastocyst-vitrification-after-trophectoderm-biopsy-for-preimplantation-genetic-screening
#19
Hsiu-Hui Chen, Chun-Chia Huang, En-Hui Cheng, Tsung-Hsien Lee, Lee-Feng Chien, Maw-Sheng Lee
Is the timing of vitrification after trophectoderm (TE) biopsy associated with successful implantation and pregnancy after the embryo transfer of blastocysts subjected to preimplantation genetic screening (PGS)? In this retrospective cohort study, 1329 blastocysts from 223 patients were subjected to TE biopsy for performing array comparative genomic hybridization (CGH) tests. The PGS and frozen blastocyst transfer (FET) cycles were performed from December 2012 to May 2015. Only the good quality and expanded blastocysts on day 5 or 6 were selected for biopsy...
2017: PloS One
https://www.readbyqxmd.com/read/28958871/two-year-clinical-outcome-after-a-single-cryoballoon-ablation-procedure-a-comparison-of-first-and-second-generation-cryoballoons
#20
Alexandre Zhao, Fabien Squara, Eloi Marijon, Olivier Thomas
BACKGROUND: The ablation of paroxysmal atrial fibrillation (PAF) by cryoballoon has increased dramatically in recent years. However, there are few data comparing first- and second-generation cryoballoons. AIM: To compare safety and mid-term (2-year) efficacy of first- and second-generation cryoballoons in PAF ablation, using cryoballoon size tailored to pulmonary vein anatomy. METHODS: In this single-centre study, we included the last 50 consecutive PAF patients who underwent cryoballoon-based pulmonary vein isolation using the first-generation cryoballoon (CB-1) and the first 50 patients using the second-generation cryoballoon (CB-2)...
October 2017: Archives of Cardiovascular Diseases
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