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https://www.readbyqxmd.com/read/28339772/heterologous-desensitization-of-cardiac-%C3%AE-adrenergic-signal-via-hormone-induced-%C3%AE-ar-arrestin-pde4-complexes
#1
Qian Shi, Minghui Li, Delphine Mika, Qin Fu, Sungjin Kim, Jason Phan, Ao Shen, Gregoire Vandecasteele, Yang K Xiang
Aims: Cardiac β-adrenergic receptor (βAR) signaling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Methods and results: Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists...
February 21, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28335220/pde5-inhibitors-loaded-nanovesicles-physico-chemical-properties-and-in-vitro-antiproliferative-activity
#2
Roberta F De Rose, Maria Chiara Cristiano, Marilena Celano, Valentina Maggisano, Ada Vero, Giovanni Enrico Lombardo, Martina Di Francesco, Donatella Paolino, Diego Russo, Donato Cosco
Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase...
May 18, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28332240/lower-urinary-tract-symptoms-benign-prostatic-hypertrophy-and-vascular-function-role-of-the-nitric-oxide-phosphodiesterase-type-5-cyclic-guanosine-3-5-monophosphate-pathway
#3
REVIEW
Yukihito Higashi
It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy...
March 22, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28330503/caffeine-modulates-glucocorticoid-induced-expression-of-ctgf-in-lung-epithelial-cells-and-fibroblasts
#4
Markus Fehrholz, Kirsten Glaser, Christian P Speer, Silvia Seidenspinner, Barbara Ottensmeier, Steffen Kunzmann
BACKGROUND: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants...
March 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28329460/model-based-comparison-of-the-normal-and-fontan-circulatory-systems-part-iii
#5
Raymond L Watrous, Alvin J Chin
BACKGROUND: For patients with the Fontan circulatory arrangement, angiotensin-converting enzyme inhibition, guanylate cyclase activation, phosphodiesterase 5 inhibition, and endothelin receptor antagonism have so far resulted in little or no improvement in [Formula: see text] or peak cardiac index (CI), suggesting that our understanding of the factors that most impact the exercise hemodynamics is incomplete. METHODS: To facilitate comparisons with clinical reports of the exercise performance of preadolescent Fontan patients, we rescaled our previously reported computational models of a two-year-old normal child and similarly aged Fontan patient, extended our Fontan model to capture the nonlinear relationship between flow and resistance quantified from previous computational fluid dynamic analyses of the total cavopulmonary connection (TCPC), and added respiration as well as skeletal muscle contraction...
March 2017: World Journal for Pediatric & Congenital Heart Surgery
https://www.readbyqxmd.com/read/28322591/insight-into-the-structural-requirements-of-pyrimidine-based-phosphodiesterase-10a-pde10a-inhibitors-by-multiple-validated-3d-qsar-approaches
#6
A K Halder, S A Amin, T Jha, S Gayen
Schizophrenia is a complex disorder of thinking and behaviour (0.3-0.7% of the population is affected). The over-expression of phosphodiesterase 10A (PDE10A) enzyme may be a potential target for schizophrenia and Huntington's disease. Because 3D QSAR analysis is one of the most frequently used modelling techniques, in the present study, five different 3D QSAR tools, namely CoMFA, CoMSIA, kNN-MFA, Open3DQSAR and topomer CoMFA methods, were used on a dataset of pyrimidine-based PDE10A inhibitors. All developed models were validated internally and externally...
March 21, 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28321644/vinpocetine-attenuates-pathological-cardiac-remodeling-by-inhibiting-cardiac-hypertrophy-and-fibrosis
#7
Mei-Ping Wu, Yi-Shuai Zhang, Xiangbin Xu, Qian Zhou, Jian-Dong Li, Chen Yan
PURPOSE: Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II)...
March 20, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28320886/optogenetic-module-for-dichromatic-control-of-c-di-gmp-signaling
#8
Min-Hyung Ryu, Anastasia Fomicheva, Oleg V Moskvin, Mark Gomelsky
Many aspects of bacterial physiology and behavior including motility, surface attachment, and cell cycle, are controlled by the c-di-GMP-dependent signaling pathways on the scale of seconds-to-minutes. Interrogation of such processes in real time requires tools for introducing rapid and reversible changes in intracellular c-di-GMP levels. Inducing expression of genes encoding c-di-GMP synthetic (diguanylate cyclases) and degrading (c-di-GMP phosphodiesterase) enzymes by chemicals may not provide adequate temporal control...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28320185/the-antiepileptogenic-effect-of-low-frequency-stimulation-on-perforant-path-kindling-involves-changes-in-regulators-of-g-protein-signaling-in-rat
#9
Simin Namvar, Yaghoub Fathollahi, Mohammad Javan, Maryam Zeraati, Mohammad Mohammad-Zadeh, Amir Shojaei, Javad Mirnajafi-Zadeh
G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of αs- and αi-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28316997/sildenafil-can-affect-innate-and-adaptive-immune-system-in-both-experimental-animals-and-patients
#10
REVIEW
Monika Kniotek, Agnieszka Boguska
Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28306529/in-vitro-inhibition-of-phosphodiesterase-5-and-arginase-activities-from-rat-penile-tissue-by-two-nigerian-herbs-hunteria-umbellata-and-anogeissus-leiocarpus
#11
Ganiyu Oboh, Adeniyi Abiodun Adebayo, Ayokunle Olubode Ademosun, Aline August Boligon
BACKGROUND: Anogeissus leiocarpus and Hunteria umbellata have been reportedly used in traditional medicine for the management of erectile dysfunction (ED). However, the scientific basis for their use has not been well established. Therefore, this study was designed to investigate the inhibitory effects of water extractable phytochemicals of H. umbellata and A. leiocarpus on phosphodiesterase-5 (PDE-5) and arginase as well as pro-oxidants induced lipid peroxidation in rat penile tissue...
March 17, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28303689/non-healing-ischaemic-digital-ulcer-in-a-systemic-sclerosis-patient-a-challenging-clinical-case
#12
Sophie Blaise, Matthieu Roustit, Alexandra Forli, Bernard Imbert, Jean-Luc Cracowski
Ischaemic digital ulcers (DUs) are an indicator of the severity of the microangiopathy in patients with systemic sclerosis (SSc). DUs are a frequent complication, affecting about 50% of patients with SSc, and are often recurrent. In cross-sectional studies involving patients with SSc, the frequency of ischaemic DUs was 12-16% with a major impact on hand function and quality of life. Effective therapy for DUs remains elusive. Intravenous iloprost has been demonstrated to have a positive effect on healing of active DUs...
March 16, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28302926/long-term-effect-of-sildenafil-on-echocardiographic-parameters-in-dogs-with-asymptomatic-myxomatous-mitral-valve-degeneration
#13
Anusak Kijtawornrat, Siripen Komolvanich, Nakkawee Saengklub, Prapawadee Pirintr, Pakit Boonpala, Chollada Buranakarl
Sildenafil is a selective phosphodiesterase-5 inhibitor that has been demonstrated to delay ventricular remodeling in humans and experimental animals. The aim of this prospective study was to assess the chronic effects of sildenafil administration on echocardiographic indices and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in dogs with naturally occurring, asymptomatic myxomatous mitral valve degeneration. Thirty client-owned dogs with ACVIM class B1 or B2 were enrolled. Dogs were randomly assigned to treatment (sildenafil 1-3 mg/kg, PO, BID for 180 days) or control groups...
March 11, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28302718/a-unique-choanoflagellate-enzyme-rhodopsin-with-cyclic-nucleotide-phosphodiesterase-activity
#14
Kazuho Yoshida, Satoshi P Tsunoda, Leonid S Brown, Hideki Kandori
Photoactivated adenylyl cyclase (PAC) and guanylyl cyclase rhodopsin (Rh-GC) increase the concentrations of intracellular cyclic nucleotides upon illumination, serving as promising second-generation tools in optogenetics. To broaden arsenal of such tools, it is desirable to have light-activatable enzymes which can decrease cyclic nucleotide concentrations in cells. Here, we report on an unusual microbial rhodopsin which may be able to meet the demand. It is found in the choanoflagellate Salpingoeca rosetta and contains a C-terminal cyclic nucleotide phosphodiesterase (PDE) domain...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302034/co-morbid-erectile-dysfunction-ed-and-antidepressant-treatment-in-a-patient-a-management-challenge
#15
Maszaidi Zainol, Hatta Sidi, Jaya Kumar, Srijit Das, Shaiful Ismail, Muhammad Hizri Hatta, Najwa Baharudin, Arun Ravindran
Across the globe, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are commonly prescribed psychopharmacological agents for patients with co-morbid mental-health problem and sexual dysfunction (SD). The serotonergic and/or noradrenergic ADs, although is an effective agent are not without SD side-effects, especially erectile dysfunction (ED). ED is an inability to achieve, or maintain an erection for satisfactory sexual intercourse during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who are on AD...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28300440/review-of-atopic-dermatitis-and-topical-therapies
#16
Julia N Mayba, Melinda J Gooderham
Atopic dermatitis is one of the most common skin disorders in the developed world, affecting up to 20% of children and 1% to 3% of adults. This review concisely explains the pathophysiology and epidemiology of atopic dermatitis, as well as potential challenges facing its successful treatment. Furthermore, mainstay topical treatment modalities are evaluated, such as emollients, topical corticosteroids, and topical calcineurin inhibitors. The use of topical corticosteroids and topical calcineurin inhibitors in combination is discussed, as studies have indicated encouraging results...
December 1, 2016: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28299329/angiotensin-1-7-downregulates-diabetes-induced-cgmp-phosphodiesterase-activation-in-rat-corpus-cavernosum
#17
Gursev S Dhaunsi, Mariam Yousif, Batoul Makki, Saghir Akhtar, Ibrahim F Benter
Molecular mechanisms of the beneficial effects of angiotensin-(1-7), Ang-(1-7), in diabetes-related complications, including erectile dysfunction, remain unclear. We examined the effect of diabetes and/or Ang-(1-7) treatment on vascular reactivity and cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) in corpus cavernosum. Male Wistar rats were grouped as (1) control, (2) diabetic (streptozotocin, STZ, treated), (3) control + Ang-(1-7), and (4) diabetic + Ang-(1-7). Following 3 weeks of Ang-(1-7) treatment subsequent to induction of diabetes, rats were sacrificed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28298895/two-phase-modulation-of-formula-see-text-entry-and-cl-formula-see-text-exchanger-in-submandibular-glands-cells-by-dexmedetomidine
#18
Minjeong Ji, Chul-Kyu Park, Jin Woo Lee, Kook Yang Park, Kuk Hui Son, Jeong Hee Hong
Dexmedetomidine (Dex), a highly selective α2-adrenoceptor agonist, attenuates inflammatory responses induced by lipopolysaccharide (LPS) and induces sedative and analgesic effects. Administration of Dex also reduces salivary secretion in human subjects and inhibits osmotic water permeability in rat cortical collecting ducts. However, little is known about the mechanisms underlying the effects of Dex on salivary glands fluid secretion. We demonstrated the α2-adrenoceptor expression in the basolateral membrane of mouse submandibular glands (SMG)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28298439/selective-export-of-autotoxin-from-the-endoplasmic-reticulum
#19
Lin Lyu, Baolu Wang, Chaoyang Xiong, Xiaotian Zhang, Xiaoyan Zhang, Junjie Zhang
Autotaxin (ATX) or ecto-nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid (LPA) generation. The mechanism of ATX protein trafficking is largely unknown. Here we demonstrated that p23, a member of the p24 protein family, was the protein sorting receptor required for ER export of ATX. A di-phenylalanine (F838/F839) motif in human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296277/effect-of-icariin-in-combination-with-daily-sildenafil-on-penile-atrophy-and-erectile-dysfunction-in-a-rat-model-of-bilateral-cavernous-nerves-injury
#20
Y Xu, H Xin, Y Wu, R Guan, H Lei, X Fu, Z Xin, Y Yang
The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis...
March 10, 2017: Andrology
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