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  1 / 1937 MEDLINE  
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[PMID]:29318581
[Au] Autor:Vietto V; Franco JV; Saenz V; Cytryn D; Chas J; Ciapponi A
[Ad] Endereço:Family and Community Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
[Ti] Título:Prostanoids for critical limb ischaemia.
[So] Source:Cochrane Database Syst Rev;1:CD006544, 2018 01 10.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010. OBJECTIVES: To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials. SELECTION CRITERIA: Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author. MAIN RESULTS: For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.
[Mh] Termos MeSH primário: Isquemia/tratamento farmacológico
Perna (Membro)/irrigação sanguínea
Doenças Vasculares Periféricas/tratamento farmacológico
Prostaglandinas/uso terapêutico
[Mh] Termos MeSH secundário: Alprostadil/uso terapêutico
Amputação/estatística & dados numéricos
Epoprostenol/uso terapêutico
Seres Humanos
Iloprosta/uso terapêutico
Isquemia/mortalidade
Perna (Membro)/cirurgia
Úlcera da Perna/tratamento farmacológico
Nafronil/uso terapêutico
Ácidos Nicotínicos/uso terapêutico
Pentoxifilina/uso terapêutico
Prostaglandinas/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Nicotinic Acids); 0 (Prostaglandins); 0 (Vasodilator Agents); 42H8PQ0NMJ (Nafronyl); A99MK953KZ (Inositol Niacinate); DCR9Z582X0 (Epoprostenol); F5TD010360 (Alprostadil); JED5K35YGL (Iloprost); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006544.pub3


  2 / 1937 MEDLINE  
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[PMID]:29315006
[Au] Autor:Pountos I; Giannoudis PV
[Ad] Endereço:a Academic Department of Trauma & Orthopaedics, School of Medicine , University of Leeds , Leeds , United Kingdom.
[Ti] Título:The role of Iloprost on bone edema and osteonecrosis: Safety and clinical results.
[So] Source:Expert Opin Drug Saf;17(3):225-233, 2018 Mar.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Iloprost is a commercially available prostaglandin I (PGI ) analogue that is shown to have antithrombotic, vasodilatative and antiproliferative effects. A number of clinical studies have shown that Iloprost can be effective in the management of bone marrow oedema and the treatment of avascular necrosis. The aim of this manuscript is to present our current understanding on the effect of Iloprost on the treatment of these conditions. Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of Iloprost on bone, bone marrow oedema and avascular necrosis. Expert opinion: The available data from the clinical studies suggest that Iloprost has limited effect in advanced stages of avascular necrosis. However, literature suggests that Iloprost administration can be a viable option in the management of bone marrow oedema and early stages of osteonecrosis. Despite these promising results its effect on bone homeostasis needs further elucidation. Moreover, further data on its safety, dosage and efficiency through randomized multicenter studies are desirable in order to reach final conclusions.
[Mh] Termos MeSH primário: Doenças da Medula Óssea/tratamento farmacológico
Edema/tratamento farmacológico
Iloprosta/uso terapêutico
Osteonecrose/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Doenças da Medula Óssea/patologia
Edema/patologia
Seres Humanos
Iloprosta/efeitos adversos
Osteonecrose/patologia
Vasodilatadores/efeitos adversos
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Vasodilator Agents); JED5K35YGL (Iloprost)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2018.1424828


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[PMID]:29180182
[Au] Autor:Chiang N; Rodda OA; Sleigh J; Vasudevan T
[Ad] Endereço:Department of Vascular Surgery, Waikato Hospital, Hamilton, New Zealand.
[Ti] Título:Perioperative warming, oxygen, and Ilomedin on oxygenation and healing in infrainguinal bypass surgery.
[So] Source:J Surg Res;220:197-205, 2017 Dec.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Perioperative adjuncts are utilized across surgical specialities with the goal of improving patient outcomes. High-dose oxygen and extended warming are shown to increase wound collagen deposition during abdominal surgery. Prostacyclin is shown to improve limb salvage and patency rate in infrainguinal bypass (IIB) surgery. This study evaluated the impact of these adjuncts on healing and perfusion post IIB surgery. METHODS: This randomized controlled study allocated patients undergoing IIB surgery into three treatment arms (perioperative high-dose oxygen, extended warming, and a synthetic prostacyclin) or a control group. The primary outcome was accumulation of hydroxyproline (OHP, collagen surrogate marker) as collected in polytetrafluoroethylene implants on day 5. Secondary outcomes included levels of growth factors and cytokines, and tissue oxygenation of the wound and foot as measured by hyperspectral technology and ankle-brachial pressure index. Clinical outcomes were observed to day 30, with long-term follow-up of 12 mo. RESULTS: Seventy-one patients completed the study. Comparing treatment groups with the control at day 5, there were no differences in OHP, growth factors or cytokines levels, or improvement in tissue oxygenation at the surgical incision. However, there was more flow to the foot (HT-SUM (%) change) in the Ilomedin group compared to control (0% versus -14.6%, P = 0.045). HT-deoxy was higher at the peripheries in the oxygen and temperature groups, suggesting decreased tissue oxygenation. CONCLUSIONS: The perioperative treatments did not dramatically improve oxygenation or healing of the surgical wound in IIB surgery; however, Ilomedin may result in greater flow to the peripheries.
[Mh] Termos MeSH primário: Temperatura Alta/uso terapêutico
Iloprosta/uso terapêutico
Oxigênio/administração & dosagem
Assistência Perioperatória/métodos
Enxerto Vascular
Cicatrização
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Hidroxiprolina/análise
Perna (Membro)/irrigação sanguínea
Perna (Membro)/cirurgia
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
JED5K35YGL (Iloprost); RMB44WO89X (Hydroxyproline); S88TT14065 (Oxygen)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE


  4 / 1937 MEDLINE  
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[PMID]:28476928
[Au] Autor:Gatfield J; Menyhart K; Wanner D; Gnerre C; Monnier L; Morrison K; Hess P; Iglarz M; Clozel M; Nayler O
[Ad] Endereço:Actelion Pharmaceuticals Ltd, Allschwil, Switzerland john.gatfield@actelion.com.
[Ti] Título:Selexipag Active Metabolite ACT-333679 Displays Strong Anticontractile and Antiremodeling Effects but Low -Arrestin Recruitment and Desensitization Potential.
[So] Source:J Pharmacol Exp Ther;362(1):186-199, 2017 Jul.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostacyclin (PGI ) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation, and extracellular matrix synthesis. Selexipag (Uptravi, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}- -(methylsulfonyl)acetamide) is the first nonprostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH. In this study we show that the active metabolite of selexipag and the main contributor to clinical efficacy ACT-333679 (previously known as MRE-269) behaved as a full agonist in multiple PAH-relevant receptor-distal-or downstream-cellular assays with a maximal efficacy ( ) comparable to that of the prototypic PGI analog iloprost. In PASMC, ACT-333679 potently induced cellular relaxation (EC 4.3 nM) and inhibited cell proliferation (IC 4.0 nM) as well as extracellular matrix synthesis (IC 8.3 nM). In contrast, ACT-333679 displayed partial agonism in receptor-proximal-or upstream-cAMP accumulation assays ( 56%) when compared with iloprost and the PGI analogs beraprost and treprostinil ( ∼100%). Partial agonism of ACT-333679 also resulted in limited -arrestin recruitment ( 40%) and lack of sustained IP receptor internalization, whereas all tested PGI analogs behaved as full agonists in these desensitization-related assays. In line with these in vitro findings, selexipag, but not treprostinil, displayed sustained efficacy in rat models of pulmonary and systemic hypertension. Thus, the partial agonism of ACT-333679 allows for full efficacy in amplified receptor-distal PAH-relevant readouts while causing limited activity in desensitization-related receptor-proximal readouts.
[Mh] Termos MeSH primário: Acetamidas/farmacologia
Acetatos/farmacologia
Proteínas Contráteis/antagonistas & inibidores
Contração Muscular/efeitos dos fármacos
Pirazinas/farmacologia
beta-Arrestinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Proliferação Celular/efeitos dos fármacos
Cricetinae
Cricetulus
AMP Cíclico/metabolismo
Epoprostenol/análogos & derivados
Epoprostenol/farmacologia
Matriz Extracelular/efeitos dos fármacos
Matriz Extracelular/metabolismo
Seres Humanos
Hipertensão Pulmonar/tratamento farmacológico
Hipertensão Pulmonar/fisiopatologia
Iloprosta/farmacologia
Masculino
Relaxamento Muscular/efeitos dos fármacos
Ratos
Ratos Endogâmicos SHR
Ratos Wistar
Receptores de Epoprostenol/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid); 0 (Acetamides); 0 (Acetates); 0 (Contractile Proteins); 0 (Pyrazines); 0 (Receptors, Epoprostenol); 0 (beta-Arrestins); 5EXC0E384L (selexipag); DCR9Z582X0 (Epoprostenol); E0399OZS9N (Cyclic AMP); JED5K35YGL (Iloprost); RUM6K67ESG (treprostinil)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170507
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.116.239665


  5 / 1937 MEDLINE  
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[PMID]:28441653
[Au] Autor:Truse R; Hinterberg J; Schulz J; Herminghaus A; Weber A; Mettler-Altmann T; Bauer I; Picker O; Vollmer C
[Ad] Endereço:Department of Anesthesiology, Düsseldorf University Hospital, Düsseldorf, Germany.
[Ti] Título:Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.
[So] Source:J Vasc Res;54(2):109-121, 2017.
[Is] ISSN:1423-0135
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. METHODS: In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. RESULTS: During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. CONCLUSIONS: During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function.
[Mh] Termos MeSH primário: Absorção Gástrica/efeitos dos fármacos
Mucosa Gástrica/efeitos dos fármacos
Iloprosta/administração & dosagem
Microcirculação/efeitos dos fármacos
Nitroglicerina/administração & dosagem
Choque Hemorrágico/tratamento farmacológico
Vasodilatadores/administração & dosagem
[Mh] Termos MeSH secundário: Administração Tópica
Animais
Modelos Animais de Doenças
Cães
Feminino
Mucosa Gástrica/irrigação sanguínea
Mucosa Gástrica/metabolismo
Oxigênio/sangue
Oxiemoglobinas/metabolismo
Permeabilidade
Choque Hemorrágico/sangue
Choque Hemorrágico/fisiopatologia
Sacarose/sangue
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oxyhemoglobins); 0 (Vasodilator Agents); 57-50-1 (Sucrose); G59M7S0WS3 (Nitroglycerin); JED5K35YGL (Iloprost); S88TT14065 (Oxygen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1159/000464262


  6 / 1937 MEDLINE  
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[PMID]:28373136
[Au] Autor:Foudi N; Ozen G; Amgoud Y; Louedec L; Choqueux C; Badi A; Kotelevets L; Chastre E; Longrois D; Norel X
[Ad] Endereço:Laboratoire des maladies cardiovasculaires d'origine génétique et nutritionnelle, University Setif 1, Algeria; Department of Pharmacy, Faculty of Medicine, University Setif 1, Algeria.
[Ti] Título:Decreased vasorelaxation induced by iloprost during acute inflammation in human internal mammary artery.
[So] Source:Eur J Pharmacol;804:31-37, 2017 Jun 05.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cyclooxygenase-2 (COX-2) induction in human internal mammary arteries (IMA) under inflammatory conditions has been associated with attenuated norepinephrine (NE)-induced vasoconstriction. This effect was associated with increased prostaglandin (PG) E and prostacyclin (PGI ) releases. The present study was designed to assess the role of these PG and their receptors (EP and IP, respectively) on the vascular reactivity during acute inflammation. Isolated IMA were cultured in the absence (Control conditions) or presence (Inflammatory conditions) of both interleukin-1 beta (IL-1ß) and lipopolysaccharide (LPS). The vasorelaxation and the increased content of cyclic adenosine monophosphate (cAMP) induced by iloprost, a PGI analogue, were significantly reduced under inflammatory conditions and restored in preparations cultured with the IP antagonist (CAY10441). Decreased cAMP levels under inflammatory conditions are due to at least increased phosphodiesterase (PDE) 4B expression. On the other hand, PGE , thromboxane analogues and EP agonists-induced vasoconstrictions were not affected under inflammatory conditions. No vasorelaxation was observed with PGD , PGE or the EP2/4 agonists in pre-contracted IMA. Finally, using RT-qPCR and immunohistochemistry, the COX-2, IP receptor and PGI synthase (PGIS) were detected. A significant increase of COX-2 and moderate increase of IP mRNA expression was observed under inflammatory conditions, whereas PGIS mRNA level was not affected. This study demonstrates that PGI /IP receptor signalling and PGI -induced relaxation are impaired in human IMA during acute inflammation, whereas the responses induced by other prostanoids are not affected. These results could explain some of the mechanisms of vascular dysfunction reported in inflammatory conditions.
[Mh] Termos MeSH primário: Iloprosta/farmacologia
Artéria Torácica Interna/efeitos dos fármacos
Artéria Torácica Interna/fisiopatologia
Doenças Vasculares/fisiopatologia
Vasodilatação/efeitos dos fármacos
[Mh] Termos MeSH secundário: Doença Aguda
Idoso
AMP Cíclico/metabolismo
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Inflamação/metabolismo
Inflamação/fisiopatologia
Masculino
Artéria Torácica Interna/metabolismo
Prostaglandinas/agonistas
Receptores de Prostaglandina/metabolismo
Doenças Vasculares/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prostaglandins); 0 (Receptors, Prostaglandin); E0399OZS9N (Cyclic AMP); JED5K35YGL (Iloprost)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  7 / 1937 MEDLINE  
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[PMID]:28340234
[Au] Autor:Lüders S; Friedrich S; Ohrndorf S; Glimm AM; Burmester GR; Riemekasten G; Backhaus M
[Ad] Endereço:Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin.
[Ti] Título:Detection of severe digital vasculopathy in systemic sclerosis by colour Doppler sonography is associated with digital ulcers.
[So] Source:Rheumatology (Oxford);56(11):1865-1873, 2017 Nov 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective: Colour Doppler ultrasonography (CDUS) is very important in general vascular diagnostic procedures. Its role in determining the extent of vasculopathy in Systemic Sclerosis (SSc) needs further investigation. The aim of this study was to compare the presence of altered arteries with nailfold capillaroscopy and clinical signs of ischaemia, that is, digital ulcers or pitting scars (DU/PS). A feasible CDUS protocol is provided. Methods: Two thousand five hundred and twenty-eight arteries of the fingers, palms and wrists from 79 SSc patients (32 arteries per patient) were examined using CDUS. Furthermore, nailfold capillaroscopy, clinical and laboratory data were evaluated. Results: Narrowed or occluded lumens were seen in 39.8% of all assessable arteries (n = 2489) and 48.9% of all proper palmar digital arteries (n = 1564) but only 15.6% (P < 0.0001) of proximal arteries (n = 924). Fingerwise analyses presented significant coincidence of pathological CDUS findings and DU/PS (P = 0.0009). Pathological CDUS findings were also associated with elevated CRP concentrations, current or past smoking with ⩾20 pack-years, male gender and present or past DU/PS. Receiver operating characteristic curve analysis (area under the curve = 0.727) suggested a cut-off value of ⩾20% pathological vessels (sensitivity: 90.7%; specificity: 47.8%) for the presence of DU/PS. An examination protocol focusing on the right-hand digits II-V (proper palmar digital arteries) revealed similar results (area under the curve = 0.751; sensitivity: 93.0%; specificity: 43.5%). Conclusion: CDUS of hand and finger arteries allows measurement of the extent of SSc vasculopathy, which is associated with clinical signs of chronic malperfusion. A shortened examination protocol of CDUS (right-hand digits II-V; 15 min instead of 45 min examination time) could complement vascular diagnostics in SSc.
[Mh] Termos MeSH primário: Dedos
Doença Arterial Periférica/diagnóstico por imagem
Escleroderma Sistêmico/complicações
Úlcera Cutânea/diagnóstico por imagem
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos alfa/uso terapêutico
Adulto
Idoso
Antagonistas de Receptores de Angiotensina/uso terapêutico
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Proteína C-Reativa/metabolismo
Bloqueadores dos Canais de Cálcio/uso terapêutico
Antagonistas dos Receptores de Endotelina/uso terapêutico
Feminino
Seres Humanos
Iloprosta/uso terapêutico
Masculino
Angioscopia Microscópica
Meia-Idade
Doença Arterial Periférica/tratamento farmacológico
Doença Arterial Periférica/epidemiologia
Doença Arterial Periférica/etiologia
Inibidores da Fosfodiesterase 5/uso terapêutico
Curva ROC
Escleroderma Sistêmico/epidemiologia
Escleroderma Sistêmico/metabolismo
Sensibilidade e Especificidade
Úlcera Cutânea/etiologia
Fumar/epidemiologia
Ultrassonografia Doppler em Cores
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic alpha-Antagonists); 0 (Angiotensin Receptor Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Calcium Channel Blockers); 0 (Endothelin Receptor Antagonists); 0 (Phosphodiesterase 5 Inhibitors); 0 (Vasodilator Agents); 9007-41-4 (C-Reactive Protein); JED5K35YGL (Iloprost)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex045


  8 / 1937 MEDLINE  
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[PMID]:28218209
[Au] Autor:Xu QX; Yang YH; Geng J; Zhai ZG; Gong JN; Li JF; Tang X; Wang C
[Ad] Endereço:Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020; Department of Respiratory Medicine, Capital Medical Univ
[Ti] Título:Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension.
[So] Source:Chin Med J (Engl);130(4):382-391, 2017 02 20.
[Is] ISSN:0366-6999
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls. METHODS: We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test. RESULTS: The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381). CONCLUSIONS: The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.
[Mh] Termos MeSH primário: Hipertensão Pulmonar Primária Familiar/tratamento farmacológico
Hipertensão Pulmonar/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Adulto
Idoso
Pressão Arterial/efeitos dos fármacos
Fator Natriurético Atrial/metabolismo
Bloqueadores dos Canais de Cálcio/administração & dosagem
Bloqueadores dos Canais de Cálcio/uso terapêutico
Endarterectomia
Hipertensão Pulmonar Primária Familiar/fisiopatologia
Feminino
Hemodinâmica/efeitos dos fármacos
Seres Humanos
Hipertensão Pulmonar/fisiopatologia
Iloprosta/administração & dosagem
Iloprosta/uso terapêutico
Masculino
Meia-Idade
Precursores de Proteínas/metabolismo
Estudos Retrospectivos
Software
Vasodilatadores/administração & dosagem
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (N-terminal proatrial natriuretic peptide); 0 (Protein Precursors); 0 (Vasodilator Agents); 85637-73-6 (Atrial Natriuretic Factor); JED5K35YGL (Iloprost)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE
[do] DOI:10.4103/0366-6999.199829


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[PMID]:28119496
[Au] Autor:Han X; Zhang Y; Dong L; Fang L; Chai Y; Niu M; Yu Y; Liu L; Yang X; Qu S; Li S
[Ad] Endereço:Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
[Ti] Título:Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost.
[So] Source:Respir Care;62(4):489-496, 2017 Apr.
[Is] ISSN:1943-3654
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Monotherapy and sequential combination therapy have been widely used in the treatment of pulmonary arterial hypertension (PAH). There is limited evidence for initial combination therapy in patients with PAH, particularly those with World Health Organization (WHO) functional class III or IV. METHODS: Twenty-seven consecutive treatment-naive PAH subjects with WHO functional class III or IV PAH were randomized into 3 groups with a 1:1:1 ratio: a combination therapy group with 125 mg of bosentan twice daily plus 10 µg of iloprost 4-6 times/d; a bosentan monotherapy group with 125 mg of bosentan twice daily; and a iloprost monotherapy group with 10 µg of iloprost 4-6 times/d. Clinical and hemodynamic data were collected at baseline, 6 weeks, and 3 months. The primary end point was the change in the 6-min walk distance (6MWD) from baseline values. RESULTS: At baseline, there were no differences in demographics, WHO classification, hemodynamics, classification of PAH, or 6MWD among the 3 groups. The 6MWD significantly improved in the combination therapy group compared with the bosentan monotherapy and iloprost monotherapy groups at week 6 ( = .001) and after 3 months ( < .001), respectively. Secondary end points significantly improved in the combination therapy group for mean pulmonary artery pressure, cardiac index, and WHO functional classification after 3 months of treatment and for N-terminal pro-brain natriuretic peptide, Minnesota Living with Heart Failure questionnaire scores, and P after 6 weeks and 3 months of treatment, compared with the monotherapy groups. CONCLUSIONS: Initial combination therapy in treatment-naive PAH subjects with WHO functional class III or IV can significantly improve 6MWD, hemodynamics, and quality of life compared with monotherapy. Further studies with large samples and placebo controls are required to assess the tolerability and efficacy of initial combination therapy in patients with PAH. (ClinicalTrials.gov registration NCT01712997).
[Mh] Termos MeSH primário: Anti-Hipertensivos/administração & dosagem
Hipertensão Pulmonar/tratamento farmacológico
Iloprosta/administração & dosagem
Sulfonamidas/administração & dosagem
Vasodilatadores/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Quimioterapia Combinada
Feminino
Hemodinâmica/efeitos dos fármacos
Seres Humanos
Hipertensão Pulmonar/fisiopatologia
Masculino
Artéria Pulmonar/fisiopatologia
Qualidade de Vida
Fatores de Tempo
Resultado do Tratamento
Teste de Caminhada
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Sulfonamides); 0 (Vasodilator Agents); JED5K35YGL (Iloprost); Q326023R30 (bosentan)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.4187/respcare.05280


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[PMID]:28060719
[Au] Autor:Beck F; Geiger J; Gambaryan S; Solari FA; Dell'Aica M; Loroch S; Mattheij NJ; Mindukshev I; Pötz O; Jurk K; Burkhart JM; Fufezan C; Heemskerk JW; Walter U; Zahedi RP; Sickmann A
[Ad] Endereço:Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany.
[Ti] Título:Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition.
[So] Source:Blood;129(2):e1-e12, 2017 Jan 12.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin αIIbß3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We applied quantitative temporal phosphoproteomics to study ADP-mediated signaling at unprecedented molecular resolution. Furthermore, to mimic the antagonistic efficacy of endothelial-derived prostacyclin, we determined how Iloprost reverses ADP-mediated signaling events. We provide temporal profiles of 4797 phosphopeptides, 608 of which showed significant regulation. Regulated proteins are implicated in well-known activating functions such as degranulation and cytoskeletal reorganization, but also in less well-understood pathways, involving ubiquitin ligases and GTPase exchange factors/GTPase-activating proteins (GEF/GAP). Our data demonstrate that ADP-triggered phosphorylation occurs predominantly within the first 10 seconds, with many short rather than sustained changes. For a set of phosphorylation sites (eg, PDE3A , CALDAG-GEFI , ENSA ), we demonstrate an inverse regulation by ADP and Iloprost, suggesting that these are central modulators of platelet homeostasis. This study demonstrates an extensive spectrum of human platelet protein phosphorylation in response to ADP and Iloprost, which inversely overlap and represent major activating and inhibitory pathways.
[Mh] Termos MeSH primário: Difosfato de Adenosina/metabolismo
Plaquetas/metabolismo
Ativação Plaquetária/fisiologia
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Plaquetas/efeitos dos fármacos
Western Blotting
Seres Humanos
Iloprosta/farmacologia
Fosforilação
Ativação Plaquetária/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/farmacologia
Proteômica/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Platelet Aggregation Inhibitors); 61D2G4IYVH (Adenosine Diphosphate); JED5K35YGL (Iloprost)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-05-714048



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