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1.
Angiol Sosud Khir ; 25(4): 35-39, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31855199

RESUMO

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.


Assuntos
Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/cirurgia , Grau de Desobstrução Vascular/efeitos dos fármacos , Varfarina/uso terapêutico , Anticoagulantes/farmacologia , Artérias/efeitos dos fármacos , Artérias/cirurgia , Implante de Prótese Vascular , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/cirurgia , Humanos , Extremidade Inferior/irrigação sanguínea , Artéria Poplítea/efeitos dos fármacos , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Rivaroxabana/farmacologia , Artérias da Tíbia/efeitos dos fármacos , Artérias da Tíbia/cirurgia , Resultado do Tratamento , Varfarina/farmacologia
2.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547271

RESUMO

Diosmin is a natural compound with a wide range of biological activity, e.g., it improves lymphatic drainage, supports microcirculation, and increases venous tone, and venous elasticity, hence, it is applied in the pharmacotherapy of chronic venous disorders (CVD). The aim of this study was to assess the correlation between diosmin administration (2 × 600 mg daily) in patients suffering from CVD and the levels of selected factors influencing angiogenesis, which are involved in CVD pathophysiology. Thirty-five CVD patients were examined. Levels of plasma tumor necrosis factor alpha (TNF alpha), vascular endothelial growth factor (VEGF-A and VEGF-C); angiostatin, interleukin 6 (IL-6), fibroblast growth factor 2 (FGF2); and plasminogen (PLG) were measured with an Elisa assay before and after three months of diosmin administration. The clinical symptoms of CVD were monitored using ultrasound images, echo Doppler assay, visual analogue scale (VAS), and measurement of the leg circumference. The average content of TNF alpha, VEGF-C, VEGF-A IL-6, and FGF2 decreased after the therapy with diosmin in a significant manner; with p < 0.001, p < 0.05, p < 0.05, p < 0.01, and p < 0.01, respectively, and a significant (p < 0.05) increase in the plasma angiostatin level after the three-month treatment was found. A significant (p < 0.05) decrease in edema and the average leg circumference of the patients was observed after the therapy. Diosmin influences the angiogenic and inflammatory mechanisms involved in the pathophysiology of edema presented in patients with a different class of CVD.


Assuntos
Diosmina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Doenças Vasculares/tratamento farmacológico , Adulto , Angiostatinas/sangue , Doença Crônica , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/fisiologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Ultrassonografia Doppler , Varizes/diagnóstico por imagem , Varizes/tratamento farmacológico , Varizes/fisiopatologia , Doenças Vasculares/sangue , Doenças Vasculares/diagnóstico por imagem , Fator A de Crescimento do Endotélio Vascular/sangue , Fator C de Crescimento do Endotélio Vascular/sangue , Veias/diagnóstico por imagem , Veias/fisiopatologia
3.
Arch Pharm Res ; 42(10): 848-861, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420777

RESUMO

Vascular endothelial cells are located on the surface of the blood vessels. It has been recognized as an important barrier to the regulation of vascular homeostasis by regulating the blood flow of micro- or macrovascular vessels. Indeed, endothelial dysfunction is an initial stage of vascular diseases and is an important prognostic indicator of cardiovascular and metabolic diseases such as atherosclerosis, hypertension, heart failure, or diabetes. Therefore, in order to develop therapeutic targets for vascular diseases, it is important to understand the key factors involved in maintaining endothelial function and the signaling pathways affecting endothelial dysfunction. The purpose of this review is to describe the function and underlying signaling pathway of oxidative stress, inflammatory factors, shear stress, and epigenetic factors in endothelial dysfunction, and introduce recent therapeutic targets for the treatment of cardiovascular diseases.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Doenças Vasculares/tratamento farmacológico , Animais , Endotélio Vascular/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doenças Vasculares/metabolismo
4.
PLoS One ; 14(6): e0217723, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166961

RESUMO

BACKGROUND AND PURPOSE: The ticlopidine/Ginkgo biloba ext. combination drug (Yuclid) is used as an antiplatelet agent for prevention of vascular events since its approval in 2008. The purpose of this study is to explore the safety of ticlopidine/Ginkgo biloba combination, mainly regarding the incidence of neutropenia, through a post-marketing surveillance study. METHODS: From March 2009 to October 2015, a total of 4839 subjects had been enrolled in this study. The enrollments were conducted by 152 doctors of 89 hospitals according to the regulations for post-marketing surveillance programs in Korea. If a subject was administered the drug once, he/she was included in the safety analysis set for any adverse events and bleedings, and the primary safety evaluation regarding neutropenia was conducted in subjects who completed 3-month blood test follow-up. We predefined that 1% reduction in neutropenia incidence by ticlopidine/Ginkgo biloba ext. combination from the previously reported incidence of ticlopidine of 2.3% was clinically meaningful. RESULTS: Among the safety analysis set of 4831 patients (99.8% of the enrolled subjects), 3150 (65.1%) completed evaluation for neutropenia at 3 months which is the primary safety endpoint. The major causes of dropout were no follow-up visit at 3 months (n = 1016) and violation of the follow-up period (n = 503). Nine patients experienced neutropenia (Absolute neutrophil count [ANC] ≤ 1200mm3) and the estimated cumulative incidence at 3 months is 0.29% (95% confidence interval, 0.13%- 0.54%). Severe neutropenia (ANC ≤ 450mm3) did not occur in any patients. CONCLUSIONS: The incidence of neutropenia with addition of Ginkgo biloba ext. to ticlopidine may be lower than the previously reported incidence of neutropenia with ticlopidine, which needs to be confirmed in randomized controlled trials.


Assuntos
Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Vigilância de Produtos Comercializados , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Idoso , Estudos de Coortes , Combinação de Medicamentos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Metanálise como Assunto , República da Coreia/epidemiologia
5.
Vet Radiol Ultrasound ; 60(6): 613-632, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31243852

RESUMO

Advances in interventional radiology and surgical techniques now allow complex abdominal diseases to be more successfully treated in small animals. Abdominal vascular alterations, acquired as individual process or as complication of other lesions such as neoplasia, can be life-threatening or at least greatly limit curative interventions of underlying diseases. Computed tomography (CT) and high-definition ultrasonography are now readily available in veterinary referral centers. Yet, there is little information currently available on the use of these modalities for the diagnosis and characterization of these vascular alterations. The purpose of this article is to review the CT and ultrasonographic findings of acquired vascular diseases in the abdomen of dogs and cats, using both the veterinary and human medicine literature as references, and highlighting essential concepts through figures.


Assuntos
Doenças do Gato/diagnóstico por imagem , Doenças do Cão/diagnóstico por imagem , Circulação Esplâncnica , Doenças Vasculares/veterinária , Abdome/diagnóstico por imagem , Animais , Gatos , Cães , Trombose/diagnóstico por imagem , Trombose/veterinária , Tomografia Computadorizada por Raios X/veterinária , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/veterinária , Ultrassonografia/veterinária , Doenças Vasculares/tratamento farmacológico
6.
Arterioscler Thromb Vasc Biol ; 39(7): 1448-1457, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31043077

RESUMO

Objective- Inflammation-driven endothelial dysfunction initiates and contributes to the progression of atherosclerosis, and MPO (myeloperoxidase) has been implicated as a potential culprit. On release by circulating phagocytes, MPO is thought to contribute to endothelial dysfunction by limiting NO bioavailability via formation of reactive oxidants including hypochlorous acid. However, it remains largely untested whether specific pharmacological inhibition of MPO attenuates endothelial dysfunction. We, therefore, tested the ability of a mechanism-based MPO inhibitor, AZM198, to inhibit endothelial dysfunction in models of vascular inflammation. Approach and Results- Three models of inflammation were used: femoral cuff, the tandem stenosis model of plaque rupture in Apoe-/- mice, and C57BL/6J mice fed a high-fat, high-carbohydrate diet as a model of insulin resistance. Endothelial dysfunction was observed in all 3 models, and oral administration of AZM198 significantly improved endothelial function in the femoral cuff and tandem stenosis models only. Improvement in endothelial function was associated with decreased arterial MPO activity, determined by the in vivo conversion of hydroethidine to 2-chloroethidium, without affecting circulating inflammatory cytokines or arterial MPO content. Mechanistic studies in Mpo-/- mice confirmed the contribution of MPO to endothelial dysfunction and revealed oxidation of sGC (soluble guanylyl cyclase) as the underlying cause of the observed limited NO bioavailability. Conclusions- Pharmacological inhibition of MPO is a potential strategy to limit endothelial dysfunction in vascular inflammation. Visual Overview- An online visual overview is available for this article.


Assuntos
Aterosclerose/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Peroxidase/antagonistas & inibidores , Doenças Vasculares/tratamento farmacológico , Animais , Apolipoproteínas E/fisiologia , Aterosclerose/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Inibidores Enzimáticos/farmacologia , Inflamação/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/fisiologia , Doenças Vasculares/fisiopatologia
7.
Int Angiol ; 38(2): 83-89, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31056892

RESUMO

BACKGROUND: To show the efficacy of micronized purified flavonoid fraction (MPFF) 1000 mg in the mild cases of chronic venous disorders (CVD), i.e. in C0s-C1 patients according to the CEAP classification. METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic C0s to C4 patients according to the Clinical Etiological Anatomic Pathophysiologic (CEAP) were treated for 8 weeks by either MPFF 1000 mg once daily or MPFF 500 mg twice daily. The present post-hoc analysis is focused on the efficacy of MPFF at the daily doses of 1000 mg in the population of mild cases of the CVD (C0s-C1 patients) on lower limb discomfort, leg pain and leg heaviness using a 10-cm Visual Analog Scale (VAS), and on quality of life (QoL) using CIVIQ-20. RESULTS: In the 256 patients of the C0s-C1 subset of the study patients, lower limb discomfort improvement measured on VAS was clinically and statistically significant: -2.87±2.38 cm in the MPFF 1000 mg group and -3.30±2.36 cm in the MPFF 500 mg group (P<0.001 in both groups). Leg pain and leg heaviness VAS improved similarly: -2.77±2.58 cm in the MPFF 1000 mg group and -3.45±2.38 cm in the MPFF 500 mg group (P<0.001 in both groups), and -2.91±2.47 cm in the MPFF 1000 mg group and -3.47±2.33 cm in the MPFF 500 mg group (P<0.001 in both groups). The quality of life assessed by the CIVIQ-20 questionnaire improved significantly in both treatment groups from baseline to W8 with a mean changes of global index score of -16.53±14.18 in the MPFF 1000 mg group and -18.78±18.14 in the MPFF 500 mg group (P<0.001). CONCLUSIONS: MPFF at the daily dose of 1000 mg was shown to have a similar efficacy in mild CVD cases (C0s-C1 patients) as in the whole spectrum of patients from the main study, with a very good safety profile. These result further illustrates the interest of MPFF in the management of the mild cases of the disease at a daily dose of 1000 mg.


Assuntos
Flavonoides/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares/tratamento farmacológico , Adulto , Idoso , Doença Crônica , Método Duplo-Cego , Feminino , Flavonoides/efeitos adversos , Humanos , Internacionalidade , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários , Doenças Vasculares/fisiopatologia , Escala Visual Analógica , Adulto Jovem
8.
Int Angiol ; 38(3): 211-218, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31112025

RESUMO

The recently published European Venous Forum (EVF) Guidelines 2018 update on the management of chronic venous disorders of the lower limbs has focused on several new aspects: a new place for early symptoms, new data on microcirculation alterations, and a re-evaluation of veno-active drugs (VADs), based on new criteria. The symposium "Chronic Venous Disease (CVD): From Symptoms to Microcirculation", held at the annual meeting of the EVF on 28 June 2018 in Athens, Greece, highlighted this perspective by answering three questions: What do symptoms mean and how do they influence our choice of investigations? Is there a link between symptoms and microcirculation alterations? How to choose the right VAD for the right patient based on the updated EVF guidelines? The answers given led the speakers to three conclusions: early symptoms reveal the initial stage of CVD and patients with C0S disease should be properly diagnosed, investigated, and treated; damage to the microcirculation is likely to be the first evidence of the onset of venous disease; Ruscus+HMC+VitC has proven efficacy in randomized controlled trials, and has been given a strong recommendation (Grade 1A) by the 2018 EVF guidelines for treatment of pain, heaviness, feeling of swelling, paresthesia, and edema, and should be considered as one of the preferred treatments to relieve these symptoms in CVD patients.


Assuntos
Ácido Ascórbico/uso terapêutico , Edema/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Ruscus/química , Doenças Vasculares/tratamento farmacológico , Doença Crônica , Congressos como Assunto , Grécia , Humanos , Microcirculação , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Veias/efeitos dos fármacos
9.
Biomed Pharmacother ; 116: 108994, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112872

RESUMO

BACKGROUND & AIMS: Numerous references made clear that Triphala is revered as a multiuse therapeutic and perhaps even panacea historically. Nevertheless, the protective mechanism of Triphala on cardio-cerebral vascular diseases (CCVDs) remains not comprehensive understanding. Hence, a network pharmacology-based method was suggested in this study to address this problem. METHODS: This study was based on network pharmacology and bioinformatics analysis. Information on compounds in herbal medicines of Triphala formula was acquired from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of Triphala, candidate targets of each component and known therapeutic targets of CCVDs were collected. Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources. In addition, key targets and pathway enrichment were analyzed by STRING database and DAVID database. Moreover, we verified three of the key targets (PTGS2, MMP9 and IL6) predicted by using western blot analysis. RESULTS: Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening, and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs. And 10 compounds, which actually linked to more than three genes, are determined as crucial chemicals. Core genes in this network were IL6, TNF, VEGFA, PTGS2, CXCL8, TP53, CCL2, IL10, MMP9 and SERPINE1. And pathways in cancer, TNF signaling pathway, neuroactive ligand-receptor interaction, etc. related to CCVDs were identified. In vitro experiments, the results indicated that compared with the control group (no treatment), PTGS2, MMP9 and IL6 were up-regulated by treatment of 10 ng/mL TNF-α, while pretreatment with 20-80 µg/mL Triphala could significantly inhibit the expression of PTGS2, MMP9 and IL6. With increasing Triphala concentration, the expression of PTGS2, MMP9 and IL6 decreased. CONCLUSIONS: This study revealed the complex components and pharmacological mechanism of Triphala, and obtained some potential therapeutic targets of CCVDs, which could provide theoretical basis for the research and development of new drugs for treating CCVDs.


Assuntos
Redes Reguladoras de Genes , Extratos Vegetais/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/genética , Ciclo-Oxigenase 2/metabolismo , Ontologia Genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Metaloproteinases da Matriz/metabolismo , Extratos Vegetais/farmacocinética , Mapas de Interação de Proteínas/genética
10.
Inflammopharmacology ; 27(4): 713-722, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119443

RESUMO

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Fenilbutiratos/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo , Doenças Vasculares/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Doenças Vasculares/metabolismo
11.
Khirurgiia (Mosk) ; (3): 135-140, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30938369

RESUMO

The issues of absorption, bacterial intestinal metabolism and hepatic metabolism of diosmin are described. The main metabolites of the drug and the ways of their elimination are indicated. The article describes the main therapeutic targets and mechanisms of influence on the course of disease including effect on the venous wall tone and permeability, lymphatic drainage, inflammation and oxidative stress.


Assuntos
Diosmina/farmacologia , Flavonoides/farmacologia , Veias/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Diosmina/farmacocinética , Flavonoides/farmacocinética , Humanos , Inflamação/tratamento farmacológico , Doenças Linfáticas/tratamento farmacológico , Doenças Linfáticas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/fisiopatologia , Veias/fisiopatologia
12.
Biochem Pharmacol ; 164: 188-204, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30905657

RESUMO

A Disintegrin and Metalloproteinase (ADAM) is a family of proteolytic enzymes that possess sheddase function and regulate shedding of membrane-bound proteins, growth factors, cytokines, ligands and receptors. Typically, ADAMs have a pro-domain, and a metalloproteinase, disintegrin, cysteine-rich and a characteristic transmembrane domain. Most ADAMs are activated by proprotein convertases, but can also be regulated by G-protein coupled receptor agonists, Ca2+ ionophores and protein kinase C activators. A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) is a family of secreted enzymes closely related to ADAMs. Like ADAMs, ADAMTS members have a pro-domain, and a metalloproteinase, disintegrin, and cysteine-rich domain, but they lack a transmembrane domain and instead have characteristic thrombospondin motifs. Activated ADAMs perform several functions and participate in multiple cardiovascular processes including vascular smooth muscle cell proliferation and migration, angiogenesis, vascular cell apoptosis, cell survival, tissue repair, and wound healing. ADAMs may also be involved in pathological conditions and cardiovascular diseases such as atherosclerosis, hypertension, aneurysm, coronary artery disease, myocardial infarction and heart failure. Like ADAMs, ADAMTS have a wide-spectrum role in vascular biology and cardiovascular pathophysiology. ADAMs and ADAMTS activity is naturally controlled by endogenous inhibitors such as tissue inhibitors of metalloproteinases (TIMPs), and their activity can also be suppressed by synthetic small molecule inhibitors. ADAMs and ADAMTS can serve as important diagnostic biomarkers and potential therapeutic targets for cardiovascular disorders. Natural and synthetic inhibitors of ADAMs and ADAMTS could be potential therapeutic tools for the management of cardiovascular diseases.


Assuntos
Proteínas ADAM/metabolismo , Desintegrinas/metabolismo , Endotélio Vascular/metabolismo , Trombospondinas/metabolismo , Doenças Vasculares/metabolismo , Proteínas ADAM/antagonistas & inibidores , Motivos de Aminoácidos/efeitos dos fármacos , Motivos de Aminoácidos/fisiologia , Animais , Desintegrinas/antagonistas & inibidores , Endotélio Vascular/efeitos dos fármacos , Humanos , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Trombospondinas/antagonistas & inibidores , Doenças Vasculares/tratamento farmacológico
13.
A A Pract ; 13(3): 99-101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907753

RESUMO

Spontaneous coronary artery disease is an uncommon and likely underdiagnosed cause of sudden cardiac death affecting typically young and middle-aged women. We report a case of spontaneous coronary artery disease in the postoperative period in a female patient who developed an acute coronary event after gynecologic surgery. The patient was clinically asymptomatic except for mild hemodynamic instability and ST-segment-elevation myocardial infarction seen on electrocardiogram. Spontaneous coronary artery disease was diagnosed with coronary angiography, and a pharmacological therapy was instituted with favorable results.


Assuntos
Anomalias dos Vasos Coronários/diagnóstico , Doenças Vasculares/congênito , Adulto , Aspirina/uso terapêutico , Bisoprolol/uso terapêutico , Clopidogrel/uso terapêutico , Angiografia Coronária , Anomalias dos Vasos Coronários/tratamento farmacológico , Feminino , Heparina/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Histerectomia Vaginal , Período Pós-Operatório , Doenças Vasculares/diagnóstico , Doenças Vasculares/tratamento farmacológico
14.
Autoimmun Rev ; 18(5): 501-509, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844558

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is burdened by a significant increase in cardiovascular disease (CVD) risk. Amongst CVD risk factors, endothelial dysfunction and arterial stiffness represent powerful predictors of atherosclerosis and cardiovascular events in the general population and in RA patients. METHODS: A systematic review of the literature was performed to identify the available data on the effect of non-TNF-targeted biologics licensed for the treatment of RA on endothelial function, arterial stiffness or subclinical atherosclerosis. MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science (WOS) databases were searched using a predefined strategy to identify relevant articles. RESULTS: The search strategy initially retrieved 389 records. After screening titles and abstracts, a total of 362 studies were excluded. Amongst the remaining 27 studies selected for final examination, 16 articles were included in the systematic literature review. Included studies demonstrated a significant effect of abatacept, anakinra, rituximab and tocilizumab in improving endothelial dysfunction associated with RA; the effect on arterial stiffness was less consistent and deserves further investigation. No significant effect of non-TNF-targeted biologics was observed for measures of subclinical atherosclerosis. CONCLUSION: Non-TNF-targeted biologics have been associated with favorable effects on endothelial dysfunction as already demonstrated for TNF inhibitors. Future studies are needed to ascertain the impact of this mediations on arterial stiffness in RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/complicações , Fatores Biológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Rituximab/uso terapêutico , Doenças Vasculares/etiologia
15.
Am J Hematol ; 94(6): 689-696, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30916794

RESUMO

Vaso-occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four-hundred charts of children age 3-21 years with SCA/VOE receiving parenteral opioids at 20 high-volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin-SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation-to-ED-disposition was smaller in the NSB group (2.2 vs 3.0, P = .03), while admission rates were higher (71% vs 59%, P = .01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to >50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality.


Assuntos
Anemia Falciforme/tratamento farmacológico , Serviço Hospitalar de Emergência , Manejo da Dor , Dor/tratamento farmacológico , Solução Salina/administração & dosagem , Doenças Vasculares/tratamento farmacológico , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Dor/etiologia , Dor/fisiopatologia , Estudos Retrospectivos , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia
16.
J Endocrinol Invest ; 42(9): 1117-1124, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30877658

RESUMO

BACKGROUND: Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids. OBJECTIVE: To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics. SUBJECTS AND METHODS: Single-blind randomized case-control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC-MS/MS. RESULTS: HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism. CONCLUSIONS: A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.


Assuntos
Insuficiência Adrenal/patologia , Calcinose/tratamento farmacológico , Glucocorticoides/efeitos adversos , Sistema Hipotálamo-Hipofisário/patologia , Artropatias/tratamento farmacológico , Sistema Hipófise-Suprarrenal/patologia , Articulação do Ombro/patologia , Tendinopatia/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Insuficiência Adrenal/induzido quimicamente , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Prognóstico , Método Simples-Cego
18.
Life Sci ; 221: 348-353, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30769115

RESUMO

Micro-vascular diseases and its associated complications continue to be a significant health problem worldwide. Vascular lesions from microvascular involvement lead to impaired blood flow and contribute to damage and dysfunction of one or more target organs, that is, the heart, kidneys, eyes, and nervous system. Calcium Dobesilate Drug (CAD) is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. CAD has been widely used as an antioxidant and a vascular protective agent. At present, the application of Calcium Dobesilate is mainly related to Micro-vascular damage-related diseases, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and it is found to significantly improve the related symptoms. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of these diseases. Scholars at home and abroad have studied the effectiveness, safety, and mechanisms of the related diseases, furthermore, the subjects involved patients and animal models, they have found some new clinical effects of this medicine. This paper makes a brief summary of a research progress of clinical application about Vascular injury related diseases and other aspects.


Assuntos
Dobesilato de Cálcio/metabolismo , Dobesilato de Cálcio/farmacologia , Microvasos/efeitos dos fármacos , Animais , Antioxidantes , Nefropatias Diabéticas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Humanos , Estresse Oxidativo , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo
19.
Pharm Biol ; 57(1): 38-48, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30702358

RESUMO

CONTEXT: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders. OBJECTIVES: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats. MATERIALS AND METHODS: Wistar Male rats (180-220 g) were divided (n = 10/group) as control fed a standard diet (STD), STD + C. aronia (200 mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20 mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8 weeks, and all other treatments were administered for 4 weeks. RESULTS: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90 ± 5 vs. 160 ± 11.3 µm) and adventitia (54.3 ± 3.8 vs. 93.6 ± 9.4 µm). It also lowered protein levels of TNF-α (0.51 ± 0.15 and 0.15 ± 0.16 vs. 0.1 ± 0.09%) and IL-6 (0.52 ± 0.19 vs. 1.0 ± 0.2%) in their aorta or serum (5.9 ± 0.91 vs. 12.98 ± 1.3 ng/mL and 78.1 ± 6.7 vs. 439 ± 78 pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4 ± 4.0 vs. 40.7 µM) and activity of SOD (5.7 ± 0.7 vs. 2.9 ± 0.6 U/mg) and decreased serum levels of ox-LDL-c (566.7 ± 46 vs. 1817 ± 147 ng/mL). Such effects were more profound than all other treatments. CONCLUSIONS: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.


Assuntos
Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Lipoproteínas LDL/sangue , Extratos Vegetais/farmacologia , Animais , Antioxidantes/administração & dosagem , Aorta/metabolismo , Crataegus , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Glutationa/metabolismo , Inflamação/patologia , Lipídeos/sangue , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Sinvastatina/farmacologia , Superóxido Dismutase/metabolismo , Túnica Média/metabolismo , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/patologia
20.
Arterioscler Thromb Vasc Biol ; 39(4): 635-646, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30786744

RESUMO

Nanoparticles promise to advance strategies to treat vascular disease. Since being harnessed by the cancer field to deliver safer and more effective chemotherapeutics, nanoparticles have been translated into applications for cardiovascular disease. Systemic exposure and drug-drug interactions remain a concern for nearly all cardiovascular therapies, including statins, antithrombotic, and thrombolytic agents. Moreover, off-target effects and poor bioavailability have limited the development of completely new approaches to treat vascular disease. Through the rational design of nanoparticles, nano-based delivery systems enable more efficient delivery of a drug to its therapeutic target or even directly to the diseased site, overcoming biological barriers and enhancing a drug's therapeutic index. In addition, advances in molecular imaging have led to the development of theranostic nanoparticles that may simultaneously act as carriers of both therapeutic and imaging payloads. The following is a summary of nanoparticle therapy for atherosclerosis, thrombosis, and restenosis and an overview of recent major advances in the targeted treatment of vascular disease.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Doenças Vasculares/tratamento farmacológico , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Colesterol/metabolismo , Avaliação Pré-Clínica de Medicamentos , Previsões , Humanos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Camundongos , Neointima/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/fisiopatologia , Placa Aterosclerótica/fisiopatologia , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Trombose/tratamento farmacológico
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