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D Valenzuela, F Moya, M Luco, J L Tapia
50 years ago, Northway described Broncopulmonary Dysplasia (BPD) in preterm infants exposed to mechanical ventilation. Since then, their survival has increased, nevertheless a "new BPD" has appeared and its incidence has not diminished. One of the characteristics of this pathology is the the abnormal vascular remodeling, which in its most severe expression is known as Pulmonary Hyper tension (PH); with an incidence of 17% in patients with BPD, which is proportional to the severity of the disease (33% in severe BPD), and as mortality factor (up to 48% 2-year mortality in PH-BPD)...
December 2017: Revista Chilena de Pediatría
Yi-Lin Zhang, Peng-Xiao Chen, Wei-Jie Guan, Hong-Mei Guo, Zhuo-Er Qiu, Jia-Wen Xu, Yu-Li Luo, Chong-Feng Lan, Jian-Bang Xu, Yuan Hao, Ya-Xia Tan, Ke-Nan Ye, Zhao-Rong Lun, Lei Zhao, Yun-Xin Zhu, Jiehong Huang, Wing-Hung Ko, Wei-De Zhong, Wen-Liang Zhou, Nan-Shan Zhong
Airway epithelial cells harbor the capacity of active Cl- transepithelial transport and play critical roles in modulating innate immunity. However, whether intracellular Cl- accumulation contributes to relentless airway inflammation remains largely unclear. This study showed that, in airway epithelial cells, intracellular Cl- concentration ([Cl- ]i ) was increased after Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulation via nuclear factor-κB (NF-κB)-phosphodiesterase 4D (PDE4D)-cAMP signaling pathways...
March 15, 2018: Mucosal Immunology
Taishi Nakamura, Guangshuo Zhu, Mark J Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E Kim, Kenichi Tsujita, David A Kass
BACKGROUND: Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation...
March 2018: Circulation. Heart Failure
Brijesh Kumar, John L Sorensen, Silvia T Cardona
Burkholderia cenocepacia is an opportunistic bacterium that can thrive in different environments, including the amino acid-rich mucus of the cystic fibrosis (CF) lung. B. cenocepacia responds to the nutritional conditions that mimic the CF sputum by increasing flagellin expression and swimming motility. Individual amino acids also induce swimming but not flagellin expression. Here, we show that modulation of the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) levels by the PAS-containing c-di-GMP phosphodiesterase, BCAL1069 (CdpA), regulates the swimming motility of B...
2018: Frontiers in Cellular and Infection Microbiology
Christian Viniol, Claus F Vogelmeier
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Yong-Soon Cho, Yook-Hwan Noh, Hyeong-Seok Lim, Sang-Heon Cho, Jong-Lyul Ghim, Sangmin Choe, Soon-Bae Kim, Jung-Sik Park, Sang-Koo Lee, Won-Seok Yang, Jai-Won Chang, Mi-Young Bahng, Kyun-Seop Bae
Udenafil is a phosphodiesterase-5 inhibitor used to treat erectile dysfunction. Although udenafil is not predominantly eliminated by the kidney, renal impairment can alter its secretion/transport pathways. Drug pharmacokinetics and safety must therefore be assessed in subjects with a renal impairment. We investigated the effects of impaired renal function on the pharmacokinetics and safety of a single 100-mg oral dose of udenafil in a single-dose, open-label, parallel-group study of 31 subjects. Cockcroft-Gault creatinine clearance was used to stratify these subjects into healthy controls (>80 mL·min-1 ) and individuals with mild (50 to ≤80 mL·min-1 ), moderate (30 to ≤50 mL·min-1 ), and severe (<30 mL·min-1 ) renal impairment...
March 14, 2018: Journal of Clinical Pharmacology
L V Tat'yanenko, N A Sanina, O V Dobrokhotova, A I Kotelnikov, N S Goryachev, I I Pihteleva, G I Kozub, T A Kondrateva
The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe2 (L)2 (NO)4 ] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca2+ -ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca2+ - ATPase, thus disturbing the balance of Ca2+ ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries...
January 2018: Doklady. Biochemistry and Biophysics
Justyna Niderla-Bielińska, Krzysztof Bartkowiak, Bogdan Ciszek, Eric Czajkowski, Ewa Jankowska-Steifer, Alicja Krejner, Anna Ratajska
Pentoxifylline (PTX), a non-specific inhibitor of cAMP phosphodiesterases, is commonly used for treatment of peripheral vascular disorders although its direct action on endothelial cells is not well described. The aim of this study was to determine the influence of PTX on tubule formation and mRNA expression for angiogenesis-related proteins in endothelial cell line C166 and mouse proepicardial explants cultured on collagen. C166 cells and explants were stimulated with proangiogenic cocktail containing bFGF/VEGF-A120 /VEGF-A164 and with proangiogenic cocktail enriched with PTX...
March 10, 2018: European Journal of Pharmacology
T Deng, X Duan, B Liu, Y Lan, C Cai, T Zhang, W Zhu, Z Mai, W Wu, G Zeng
This meta-analysis aimed to clarify the actual association between the phosphodiesterase type 5 inhibitors (PDE5-Is) use and the risk of melanoma in erectile dysfunction (ED) patients. A systematic literature search was conducted in online databases in October, 2016 to identify studies focusing on the association between PDE5-Is use and the risk of melanoma. Summarized multivariate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess the strength of associations. A total of six clinical trials containing more than one million participants were included...
2018: Neoplasma
M Wolf, M Ao, M B Chavez, T N Kolli, V Thumbigere-Math, K Becker, E Y Chu, A Jäger, M J Somerman, B L Foster
Previous studies revealed that cementum formation is tightly regulated by inorganic pyrophosphate (PPi ), a mineralization inhibitor. Local PPi concentrations are determined by regulators, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which increases PPi concentrations by adenosine triphosphate hydrolysis. Orthodontic forces stimulate alveolar bone remodelling, leading to orthodontic tooth movement (OTM). To better understand how disturbed mineral metabolism and the resulting altered periodontal structures affect OTM, we employed Enpp1 mutant mice that feature reduced PPi and increased cervical cementum in a model of OTM induced by a stretched closed-coil spring ligated between the maxillary left first molar and maxillary incisors...
March 1, 2018: Journal of Dental Research
Kilmer S McCully
The indoleamine hormone melatonin is synthesized by the pineal gland, controls circadian rhythm, and is dependent upon adenosyl methionine for enzymatic synthesis of melatonin from N-acetyl serotonin. Pineal melatonin secretion declines dramatically with aging and dementia. Elevated plasma homocysteine is a risk factor for atherosclerosis and Alzheimer's disease, and the marked decline in adenosyl methionine with aging leads to dysregulation of methionine metabolism and hyperhomocysteinemia. Thioretinaco ozonide is a disulfonium complex formed from thioretinamide, cobalamin, and ozone, which binds the alpha and gamma-phosphate groups of adenosine triphosphate (ATP) and oxygen in the process of oxidative phosphorylation within mitochondria...
January 2018: Annals of Clinical and Laboratory Science
Rui-Dong Duan
Alkaline sphingomyelinase cleaves phosphocholine from sphingomyelin, platelet-activating factor, lysophosphatidylcholine, and less effectively phosphatidylcholine. The enzyme shares no structure similarities with acid or neutral sphingomyelinase but belongs to ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) family and therefore is also called NPP7 nowadays. The enzyme is expressed in the intestinal mucosa in many species and additionally in human liver. The enzyme in the intestinal tract has been extensively studied but not that in human liver...
February 27, 2018: World Journal of Hepatology
Xin Zhao, Jinyu Liu, Shijun Yang, Dandan Song, Chen Wang, Chen Chen, Chengcheng Wang, Feifei Pu, Runmei Yang, Xiaoya Li, Qiuting Wang, Shasha Ge, Yulin Lin, Xiuhua Liu, Dayong Cai
Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke. The neurovascular coupling (NVC) dysfunction involves in its pathogenesis. VaD lacks suitable animal models for developing preventive therapies. This study aimed to confirm a model for preventing VaD via maintaing NVC sensitivity in rats. The model was replicated with autologous microthrombi against the background of hypercholesterolemia. A phosphodiesterase inhibitor (pentoxyfylline) was preventively administrated to confirm the role of NVC sensitivity...
March 8, 2018: European Journal of Pharmacology
Nahla Reda Sarhan, Nesreen Moustafa Omar
Tadalafil (Cialis) is one of the most commonly used phosphodiesterase type5 (PDE5) inhibitors. This work aimed to analyze the histological and ultrastructural changes provoked by chronic tadalafil administration in the rat retina, correlate between such changes and PDE5 immunoexpression and to evaluate the possible reversibility of these changes. Thirty Sprague Dawley male rats were randomly distributed into 3 groups. Control group; given 1 ml distilled water daily for 6 weeks. Tadalafil group; given tadalafil in a daily dose of 2...
March 8, 2018: Acta Histochemica
Raffaele Pesavento, Paolo Prandoni
Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon and late complication of pulmonary embolism resulting from misguided remodelling of residual pulmonary thromboembolic material and small-vessel arteriopathy. CTEPH is the only form of pulmonary hypertension (PH) potentially curable by pulmonary endarterectomy (PEA). Unfortunately, several patients have either an unacceptable risk-benefit ratio for undergoing the surgical intervention or develop persistent PH after PEA. Novel medical and endovascular therapies can be considered for them...
March 2, 2018: Thrombosis Research
Takuji Sugiyama, Yuji Narukawa, Shunsuke Shibata, Ryo Masui, Fumiyuki Kiuchi
Agarwood (jinkoh in Japanese) is a resinous wood from Aquilaria species of the family Thymelaeaceae and has been used as incense and in traditional medicines. Characteristic chromone derivatives such as agarotetrol have been isolated from agarwood. In previous study, we isolated two new 2-(2-phenylethyl)chromones together with six known compounds from MeOH extract of agarwood. Further chemical investigation of the MeOH extract led to isolation of eighteen 2-(2-phenylethyl)chromones, including three new 5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromones with stereochemistry enantiomeric to agarotetrol-type, viz...
March 10, 2018: Journal of Natural Medicines
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Alberto Ramírez Mata, César Millán Pacheco, José F Cruz Pérez, Martha Minjárez Sáenz, Beatriz E Baca
BACKGROUND: The cyclic-di-GMP (c-di-GMP) second messenger exemplifies a signaling system that regulates many bacterial behaviors of key importance; among them, c-di-GMP controls the transition between motile and sessile life-styles in bacteria. Cellular c-di-GMP levels in bacteria are regulated by the opposite enzymatic activities of diguanylate cyclases and phosphodiesterases, which are proteins that have GGDEF and EAL domains, respectively. Azospirillum is a genus of plant-growth-promoting bacteria, and members of this genus have beneficial effects in many agronomically and ecologically essential plants...
March 9, 2018: BMC Microbiology
Agnieszka Zagorska, Anna Partyka, Adam Bucki, Alicja Gawalska, Anna Czopek, Maciej Pawlowski
BACKGROUND: The phosphodiesterase 10 (PDE10) family, identified in 1999, is mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons, nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually rational subject for medicinal chemistry with potential use in the treatment of psychiatric and neurodegenerative diseases. OBJECTIVE: This review is based on peer-reviewed published articles, and summarizes the cellular and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative drug discovery...
March 8, 2018: Current Medicinal Chemistry
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