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https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#1
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28197557/doubly-charged-trimeric-cluster-ions-effective-in-mutual-chiral-recognition-of-tadalafil-and-three-proton-pump-inhibitors
#2
Lu Wang, Yunfeng Chai, Wenquan Zhu, Yuanjiang Pan, Cuirong Sun, Su Zeng
Mutual chiral recognition of four stereoisomers of tadalafil and three pairs of enantiomers of proton pump inhibitors (PPIs) including pantoprazole, lansoprazole, and omeprazole, as well as quantitative analysis of enantiomeric excess is achieved on the basis of the competitive fragmentation of doubly charged trimeric Ni(II) cluster ions. Compared with a singly charged trimeric cluster ion, a doubly charged trimeric cluster ion was proved efficient in the recognition of chiral drugs with one or multiple chiral centers, due to its rich fragmentation ions...
February 15, 2017: Analyst
https://www.readbyqxmd.com/read/28188129/enhancement-of-fracture-healing-in-the-rat-modulated-by-compounds-that-stimulate-inducible-nitric-oxide-synthase-acceleration-of-fracture-healing-via-inducible-nitric-oxide-synthase
#3
R A Rajfer, A Kilic, A S Neviaser, L M Schulte, S M Hlaing, J Landeros, M G Ferrini, E Ebramzadeh, S-H Park
OBJECTIVES: We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. MATERIALS AND METHODS: Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail...
February 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28163808/the-protective-effect-of-l-arginine-tadalafil-and-their-combination-in-rat-testes-after-ischemia-and-reperfusion-injury
#4
Gokhun Ozmerdiven, Burhan Coskun, Onur Kaygisiz, Berna Aytac Vuruskan, Burak Asiltas, Hakan Kilicarslan
INTRODUCTION: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for prevention of the ischemia reperfusion injury after testis torsion in rats. METHODS: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion...
January 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28163539/inhibition-by-tadalafil-of-contractility-of-isolated-nonpregnant-human-myometrium
#5
Sumalya Sen, Anitha Thomas, Saibal Das, Jayanta Kumar Dey, Abraham Peedicayil, Vinotha Thomas, Jacob Peedicayil
OBJECTIVE: To investigate the inhibitory effect of tadalafil on the contractility of isolated nonpregnant human myometrium. MATERIALS AND METHODS: The ability of tadalafil (25, 40, and 63 μM) to inhibit 55 mM KCl-induced contractility of isolated nonpregnant human myometrium was studied. The ability of the ATP-sensitive potassium channel blocker glibenclamide (10 μM) and the calcium-sensitive potassium channel (BKCa) blocker iberiotoxin (100 nM) to reverse the inhibitory effect of 40 μM tadalafil on 55 mM KCl-induced myometrial contractility was also studied...
October 2016: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28162817/re-efficacy-and-safety-of-tadalafil-5mg-once-daily-in-the-treatment-of-lower-urinary-tract-symptoms-associated-with-benign-prostatic-hyperplasia-in-men-aged-%C3%A2-75-years-integrated-analyses-of-pooled-data-from-multinational-randomized-placebo-controlled-clinical
#6
https://www.readbyqxmd.com/read/28150511/investigation-of-pde5-pde6-and-pde5-pde11-selective-potent-tadalafil-like-pde5-inhibitors-using-combination-of-molecular-modeling-approaches-molecular-fingerprint-based-virtual-screening-protocols-and-structure-based-pharmacophore-development
#7
Gülru Kayık, Nurcan Ş Tüzün, Serdar Durdagi
The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3',5'-cyclic guanosine monophosphate (cGMP) and/or 3',5'-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28133708/tadalafil-improves-lean-mass-and-endothelial-function-in-nonobese-men-with-mild-ed-luts-in-vivo-and-in-vitro-characterization
#8
Antonio Aversa, Simona Fittipaldi, Davide Francomano, Viviana M Bimonte, Emanuela A Greco, Clara Crescioli, Luigi Di Luigi, Andrea Lenzi, Silvia Migliaccio
PURPOSE: Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12 skeletal muscle cells in vitro. METHODS: Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m(2)) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months...
January 30, 2017: Endocrine
https://www.readbyqxmd.com/read/28123046/pde5-inhibitor-tadalafil-and-hydroxychloroquine-co-treatment-provides-synergistic-protection-against-type-2-diabetes-and-myocardial-infarction-in-mice
#9
Rui Wang, Lei Xi, Rakesh C Kukreja
Diabetes is associated with high risk of ischemic heart disease. We previously showed that phosphodiesterase 5 inhibitor - tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug, which was reported to reduce hyperglycemia in diabetic patients. Therefore we hypothesized that combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mTOR signaling, which regulates protein synthesis and cell survival...
January 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28090299/tadalafil-therapy-for-sarcoidosis-associated-pulmonary-hypertension
#10
H J Ford, R P Baughman, R Aris, P Engel, J F Donohue
Sarcoidosis-associated pulmonary hypertension (SAPH) is estimated to occur in at least 5% or more of sarcoidosis patients, and it contributes to significant morbidity and mortality. Optimal therapy for SAPH is not well established. We performed a 24-week open-label trial of tadalafil for SAPH at 2 academic medical centers. Subjects were required to have confirmed sarcoidosis plus a right heart catheterization within 12 months of enrollment showing a mean pulmonary artery pressure ≥ 25 mmHg, a pulmonary artery wedge pressure ≤ 15 mmHg, and a calculated pulmonary vascular resistance ≥ 3 Wood units...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28074456/therapeutic-efficacy-of-tadalafil-and-eriythropoietin-in-experimental-spinal-cord-injury
#11
Çağrı Kökoğlu, Emre Delen, Ali Arslantaş, Didem Arslantaş, Burcu Kökoğlu, Zühtü Özbek, Sema Uslu, Ahmet Tolgay Akıncı
BACKGROUND: This experimental study was an investigation of the efficacy of erythropoietin and tadalafil in rats with induced spinal cord injury (SCI). METHODS: Thirty-five Sprague Dawley rats were distributed into 5 groups. First group was used for normal biochemical values. Spinal cord injury was induced in 4 remaining groups with clip compression technique after laminectomy process to T10 vertebra. Second group was designated solvent group and received 1 cc physiological serum after injury...
November 2016: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/28059578/a-bayesian-meta-analytic-approach-for-safety-signal-detection-in-randomized-clinical-trials
#12
Motoi Odani, Satoru Fukimbara, Tosiya Sato
BACKGROUND/AIM: Meta-analyses are frequently performed on adverse event data and are primarily used for improving statistical power to detect safety signals. However, in the evaluation of drug safety for New Drug Applications, simple pooling of adverse event data from multiple clinical trials is still commonly used. We sought to propose a new Bayesian hierarchical meta-analytic approach based on consideration of a hierarchical structure of reported individual adverse event data from multiple randomized clinical trials...
January 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28042309/the-link-between-vascular-dysfunction-bladder-ischemia-and-aging-bladder-dysfunction
#13
REVIEW
Karl-Erik Andersson, Donna B Boedtkjer, Axel Forman
The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome. Chronic ischemia-related bladder dysfunction may progress to bladder underactivity and it would be desirable to treat not only lower urinary tract symptoms (LUTS) induced by chronic ischemia, but also the progression of the morphological bladder changes...
January 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28039187/initial-combination-therapy-with-ambrisentan-and-tadalafil-in-connective-tissue-disease-associated-pulmonary-arterial-hypertension-ctd-pah-subgroup-analysis-from-the-ambition-trial
#14
John Gerry Coghlan, Nazzareno Galiè, Joan Albert Barberà, Adaani E Frost, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Masataka Kuwana, Vallerie V McLaughlin, Andrew J Peacock, Gérald Simonneau, Jean-Luc Vachiéry, Christiana Blair, Hunter Gillies, Karen L Miller, Julia H N Harris, Jonathan Langley, Lewis J Rubin
BACKGROUND: Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. OBJECTIVE: To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial...
December 30, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28035764/alpha-pvp-as-an-active-component-of-herbal-highs-in-poland-between-2013-2015
#15
Bogumiła Byrska, Roman Stanaszek, Dariusz Zuba
Alpha-PVP (alpha-pyrrolidinovalerophenone, α-PVP) is a synthetic derivative of cathinone. It has been one of the most frequently detected new psychoactive substances (NPS) available on the drug market in recent years in Poland. The usual routes of administration of the drug include oral, insufflation, injection. Unexpectedly, we dealt with a great number of herbal samples that turned out to contain α-PVP. A total number of 352 herbal samples from 19 cases, in which we detected synthetic cathinones, were investigated in the Institute of Forensic Research (IFR) from 2013 to 2015...
December 30, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28032371/tadalafil-for-male-lower-urinary-tract-symptoms-improves-endothelial-function
#16
Kazuhiko Fukumoto, Atsushi Nagai, Ryoei Hara, Tomohiro Fujii, Yoshiyuki Miyaji
OBJECTIVES: To investigate the effects of tadalafil on vascular endothelial function and cardiovascular risk in patients with prostatic hyperplasia. METHODS: Tadalafil 5 mg was given to 20 patients with prostatic hyperplasia for whom an α1-blocker was ineffective. Voiding symptoms and vascular endothelial function were investigated before and after 4 and 12 weeks of administration, using commercial tests for vascular function and vascular endothelial function. RESULTS: The participants had a median age of 65 years, a mean body mass index of 24...
December 29, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28004593/identification-of-a-new-tadalafil-analogue-in-commercial-dietary-supplements-isopropylnortadalafil
#17
Han Na Park, Ji Hyun Lee, Sung-Kwan Park, Jongkook Lee, Sun Young Baek
A new tadalafil analogue was found in a commercial dietary supplement for enhancing sexual performance. The compound was detected by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The analogue was isolated using semi-preparative HPLC, and its accurate mass was established by two LC-high-resolution-mass spectrometers (LC-HRMS). The structure was determined by nuclear magnetic resonance (NMR) spectroscopy. The accurate mass of the compound corresponded to a molecular formula of C24H23N3O4...
February 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/27989690/comparing-the-efficacy-of-tadalafil-versus-placebo-on-pulmonary-artery-systolic-pressure-and-right-ventricular-function-in-patients-with-beta-thalassaemia-intermedia
#18
Rozita Jalalian, Ali Akbar Moghadamnia, Ahmad Tamaddoni, Soraya Khafri, Mohammadreza Iranian
BACKGROUND: Conventional oral therapies in the management of pulmonary hypertension in people without haemoglobinopathies are of limited value in thalassaemia patients because of toxicity and poor effectiveness. This study was conducted to assess the effect of tadalafil on pulmonary artery pressure and right ventricular systolic function in patients with beta-thalassaemia intermedia. METHODS: Forty-four patients with beta-thalassaemia intermedia with pulmonary hypertension based on transthoracic echocardiography (TTE) were entered in the study...
December 2, 2016: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/27988986/efficacy-and-safety-of-tadalafil-5mg-once-daily-in-the-treatment-of-lower-urinary-tract-symptoms-associated-with-benign-prostatic-hyperplasia-luts-bph-in-men-aged-75-years-or-older-integrated-analyses-of-pooled-data-from-multinational-randomised-placebo-controlled
#19
Matthias Oelke, Adrian Wagg, Yasushi Takita, Hartwig Büttner, Lars Viktrup
OBJECTIVE: To assess efficacy and safety of tadalafil in men ≥75 years with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) and additional safety in men ≥75 years with erectile dysfunction (ED). SUBJECTS AND METHODS: Integrated analysis of 12 Phase II-III randomised, double-blind and/or open-label extension studies to evaluate short-term (12-26 weeks) efficacy and short- and longer-term (42-52 weeks) safety in men <75 vs...
December 18, 2016: BJU International
https://www.readbyqxmd.com/read/27987345/retrospective-study-of-tadalafil-for-fetal-growth-restriction-impact-on-maternal-and-perinatal-outcomes
#20
Michiko Kubo, Takashi Umekawa, Yuka Maekawa, Hiroaki Tanaka, Masafumi Nii, Nao Murabayashi, Kazuhiro Osato, Yuki Kamimoto, Tomoaki Ikeda
AIM: The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes. METHODS: We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group)...
December 17, 2016: Journal of Obstetrics and Gynaecology Research
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