Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.130
Filtrar
1.
Nutrients ; 13(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808784

RESUMO

Chronic Venous Disease (CVD) is a common medical condition affecting up to 80% of the general population. Clinical manifestations can range from mild to more severe signs and symptoms that contribute to the impairment of the quality of life (QoL) of affected patients. Among treatment options, venoactive drugs such as diosmin are widely used in the symptomatic treatment in all clinical stages. The aim of this study is to determine the effectiveness of a new formulated diosmin in relieving symptoms and improving QoL in patients suffering from CVD. In this randomized, double-blind, placebo-controlled, multicenter clinical study, CVD patients with a Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system between C2 and C4 were randomized to receive a bioavailable diosmin (as µsmin® Plus) 450 mg tablet once daily or a placebo for 8 weeks. Clinical symptoms and QoL were monitored using the measurement of leg circumference, visual analogue scale (VAS) for pain, Global Index Score (GIS) and Venous Clinical Severity Score (VCSS). A total of 72 subjects completed the study. From week 4, leg edema was significantly decreased in the active group (p < 0.001). An improvement in the VAS score was observed in the active group compared to placebo at the end of treatment (p < 0.05). GIS and VCSS scores were significantly improved in the active group at week 8 (p < 0.001). No treatment related-side effects were recorded. The results of this study showed that the administration of low-dose µsmin® Plus was safe and effective in relieving symptoms and improving QoL in subjects with CVD.


Assuntos
Doença Crônica/tratamento farmacológico , Diosmina/uso terapêutico , Qualidade de Vida , Doenças Vasculares/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Edema , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Medição da Dor , Veias , Adulto Jovem
2.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652665

RESUMO

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1ß, IL-6, HIF-1α, TGF-ß, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.


Assuntos
Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Metildopa/farmacologia , Doenças Vasculares/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas In Vitro , Inflamação/genética , Inflamação/patologia , Placenta/efeitos dos fármacos , Placenta/patologia , Fator de Crescimento Placentário/genética , Gravidez , Trofoblastos/efeitos dos fármacos , Doenças Vasculares/genética , Doenças Vasculares/patologia
3.
Naunyn Schmiedebergs Arch Pharmacol ; 394(5): 1003-1007, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443616

RESUMO

Since March 2020, the world has been fighting a global pandemic caused by a new coronavirus SARS-CoV-2 (COVID-19). SARS-CoV-2 is responsible for severe acute respiratory syndrome, an airway disease that can be severe and fatal in a percentage of cases. Patients with severe COVID-19 can develop extrapulmonary lesions, with renal, hepatic, cardiac, neurological, and tissue involvement that can cause further severe complications. On December 21, 2021, the European Medicines Agency (EMA) authorized the marketing of the first COVID-19 vaccine. However, several randomized trials are ongoing to find effective, safe, and widely available treatments. The most severe stages of COVID-19 infection are characterized by a multi-system inflammatory state induced by a cytokine storm causing multi-organ injury. Epidemiologic evidence has shown that glucocorticoids (GCs), particularly dexamethasone, are used in severe, hospitalized patients with COVID-19 with good therapeutic benefit. COVID-19 can also damage the endothelial system, causing microcirculatory disturbances and consequently leading to functional organ disorders. The combination of endothelial dysfunction with a generalized inflammatory state may contribute to the general pro-coagulative state described in patients with COVID-19 with increased risk of venous and arterial occlusions. The aim of this article is to describe the therapeutic utility of GCs in stabilizing the vascular endothelial barrier in COVID-19 infection. Indeed, we believe that the stabilization of the endothelial barrier and the anti-inflammatory effect of GCs could be the main effect underlying the therapeutic efficacy in COVID-19 patients.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/complicações , COVID-19/tratamento farmacológico , Endotélio Vascular/fisiopatologia , Glucocorticoides/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Dexametasona/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Clin Rheumatol ; 27(2): 73-79, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315786

RESUMO

ABSTRACT: In daily practice, the frequent appearance of limb and/or skin necrosis, which we term "acute peripheral and/or cutaneous ischemic syndrome" (APCIS), can be a manifestation of numerous underlying diseases, or it can sometimes be a clinical phenomenon whose etiology is undefined even after a wide investigation. The mechanisms for the development of APCIS include vessel wall abnormalities (atherosclerosis, vasculitis, and calciphylaxis), embolic processes (infectious endocarditis, atrial myxoma, and cholesterol emboli), local thrombotic injuries (genetic or acquired thrombophilias and heparin- and warfarin-induced ischemia), dysproteinemias (cryoglobulinemia and cryofibrinogenemia), or venous limb gangrene. Here, we report 5 illustrative cases of APCIS with different pathogenetic mechanisms, thereby highlighting some clinical conditions that cause APCIS that may be of special interest for rheumatologists, such as antiphospholipid syndrome, primary and secondary vasculitis, and cryoproteinemias. Furthermore, we describe a large spectrum of other causes of APCIS beyond the scope of rheumatology. Because there are no validated guidelines for APCIS, we tentatively propose an initial diagnostic workup and a therapeutic approach based on full-dose anticoagulation and immunosuppressive therapy.


Assuntos
Extremidades/irrigação sanguínea , Isquemia/etiologia , Pele/irrigação sanguínea , Doenças Vasculares/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/tratamento farmacológico , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Reumatologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Doenças Vasculares/terapia
6.
Clin Neurol Neurosurg ; 201: 106436, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33383463

RESUMO

BACKGROUND: To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. METHODS: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate [8-14], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. RESULTS: Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07-1.49,p = 0.016). CONCLUSIONS: During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.


Assuntos
COVID-19/epidemiologia , Neurologia/tendências , Sociedades Médicas/tendências , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica/tendências , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Ativador de Plasminogênio Tecidual/administração & dosagem , Estados Unidos/epidemiologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/epidemiologia
8.
Geriatr Gerontol Int ; 20(11): 1067-1071, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32989840

RESUMO

AIM: To examine the association of physical exercise (PE) and medication on cognitive function in older adults with vascular risk. METHODS: This was a cross-sectional study of 478 non-demented participants aged ≥60 years with vascular risk. Management strategy included PE (mind-body exercise and/or strenuous exercise), medication, PE combined with medication and no management at all. Participation of PE was determined by self-reporting exercise engagement in the past year. Cognitive preservation was defined as a global composite z-score that was equal to or above the age and educational adjusted mean of cognitively normal older adults. Binary logistic regression was carried out to examine the association between management strategy and cognitive preservation in each exercise modality adjusted by sociodemographic, physical, mental and genetic factors. RESULTS: An association was found in preserved cognitive function for those who managed their vascular risk through PE (OR 2.5, 95% CI 1.2-5.3, P = 0.015) and in combination with medication (OR 2.1, 95% CI 1.0-4.6, P = 0.05). A similar pattern was also found in each exercise subtype. A significant short-term (OR 3.6, 95% CI 1.0-12.4, P = 0.042) to lifelong (OR 3.5, 95% CI 1.4-8.5, P = 0.006) cognitive benefit was found in MB exercise. CONCLUSION: Medication alone may be insufficient to preserve cognitive function in older adults with vascular risk. In our sample, medication in combined with PE is found to have significant impact on cognitive improvement. Mind-body exercise might be better than strenuous exercise, as a more sustainable cognitive effect is observed. Geriatr Gerontol Int 2020; 20: 1067-1071..


Assuntos
Cognição , Terapia por Exercício , Exercício Físico , Doenças Vasculares/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Doenças Vasculares/tratamento farmacológico
9.
Life Sci ; 260: 118398, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920004

RESUMO

AIMS: We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet (HFD)-fed rats. MAIN METHODS: Male Sprague-Dawley rats were fed a HFD with fructose 15% in drinking water for 16 weeks. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks. KEY FINDINGS: HFD-fed rats treated with nobiletin was significantly reduced obesity, hypertension, dyslipidemia and hyperinsulinemia. Nobiletin improved vascular endothelial function, restored creatinine clearance, and reduced plasma urea and creatinine levels, as well as urinary protein excretion. Nobiletin markedly alleviated vascular medial cross-sectional area (CSA) and collagen deposition, glomerular extracellular matrix (ECM) accumulation, and renal fibrosis. Nobiletin significantly elevated plasma adiponectin levels, together with upregulated adiponectin receptor 1 (AdipoR1) and suppressed transforming growth factor-ß1 (TGF-ß1) expression in kidney. In addition, an increase of plasma tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly attenuated after nobiletin treatment. SIGNIFICANCE: Our results suggest that nobiletin attenuates HFD-induced vascular and renal alterations in rats, which is possibly related to the modulation of AdipoR1 and TGF-ß1expression, and suppression of inflammation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Flavonas/farmacologia , Inflamação/prevenção & controle , Nefropatias/tratamento farmacológico , Receptores de Adiponectina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Doenças Vasculares/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Regulação da Expressão Gênica , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Adiponectina/genética , Fator de Crescimento Transformador beta1/genética , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia
11.
J Pharmacol Exp Ther ; 374(3): 469-478, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32631869

RESUMO

The complex pathophysiology of sickle cell anemia (SCA) involves intravascular hemolytic processes and recurrent vaso-occlusion, driven by chronic vascular inflammation, which result in the disease's severe clinical complications, including recurrent painful vaso-occlusive episodes. Hydroxyurea, the only drug frequently used for SCA therapy, is a cytostatic agent, although it appears to exert nitric oxide/soluble guanylyl cyclase (sGC) modulating activity. As new drugs that can complement or replace the use of hydroxyurea are sought to further reduce vaso-occlusive episode frequency in SCA, we investigated the effects of the sGC agonists BAY 60-2770 (sGC activator) and BAY 41-2272 (sGC stimulator) in the presence or absence of hydroxyurea on SCA vaso-occlusive mechanisms and cell recruitment both ex vivo and in vivo. These agents significantly reduced stimulated human SCA neutrophil adhesive properties ex vivo in association with the inhibition of surface ß2-integrin activation. A single administration of BAY 60-2770 or BAY 41-2272 decreased tumor necrosis factor cytokine-induced leukocyte recruitment in a mouse model of SCA vaso-occlusion. Importantly, the in vivo actions of both agonists were significantly potentiated by the coadministration of hydroxyurea. Erythroid cell fetal hemoglobin (HbF) elevation is also a major goal for SCA therapy. BAY 41-2272 but not BAY 60-2770 at the concentrations employed significantly induced γ-globin gene transcription in association with HbF production in cultured erythroleukemic cells. In conclusion, sGC agonist drugs could represent a promising approach as therapy for SCA, for use either as stand-alone treatments or in combination with hydroxyurea. SIGNIFICANCE STATEMENT: This preclinical study demonstrates that stimulators and activators of sGC are potent inhibitors of the adhesion and recruitment of leukocytes from humans and in mice with sickle cell anemia (SCA) and may represent a promising approach for diminishing vaso-occlusive episode frequency in SCA. Hydroxyurea, a drug already frequently used for treating SCA, was found to potentiate the beneficial effects of sGC agonists in in vivo studies, implying that these classes of compounds could be used alone or in combination therapy.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/metabolismo , Hidroxiureia/farmacocinética , Guanilil Ciclase Solúvel/metabolismo , Animais , Benzoatos/farmacologia , Compostos de Bifenilo/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células Eritroides/efeitos dos fármacos , Células Eritroides/metabolismo , Hemoglobina Fetal/metabolismo , Humanos , Hidrocarbonetos Fluorados/farmacologia , Células K562 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirazóis/farmacologia , Piridinas/farmacologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Vasodilatadores/farmacologia
12.
Cardiovasc Pathol ; 49: 107259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692664

RESUMO

Perivascular adipose tissue (PVAT) is a fat tissue deposit that encircles the vasculature. PVAT is traditionally known to protect the vasculature from external stimuli that could cause biological stress. In addition to the protective role of PVAT, it secretes certain biologically active substances known as adipokines that induce paracrine effects on proximate blood vessels. These adipokines influence vascular tones. There are different types of PVAT and they are phenotypically and functionally distinct. These are the white and brown PVATs. Under certain conditions, white PVAT could undergo phenotypic switch to attain a brown PVAT-like phenotype. This type of PVAT is referred to as Beige PVAT. The morphology of adipose tissue is influenced by species, age, and sex. These factors play significant roles in adipose tissue mass, functionality, paracrine activity, and predisposition to vascular diseases. The difficulty that is currently experienced in extrapolating animal models to human physiology could be traceable to these factors. Up till now, the involvement of PVAT in the development of vascular pathology is still not well understood. Brown and white PVAT contribute differently to vascular pathology. Thus, the PVAT could be a therapeutic target in curbing certain vascular diseases. In this review, knowledge would be updated on the multifaceted involvement of PVAT in vascular pathology and also explore its vascular therapeutic potential.


Assuntos
Tecido Adiposo Bege/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Artérias/patologia , Doenças Vasculares/patologia , Adipocinas/metabolismo , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Bege/fisiopatologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Adiposidade , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Artérias/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Hemodinâmica , Humanos , Mediadores da Inflamação/metabolismo , Comunicação Parácrina , Transdução de Sinais , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologia
13.
Ann R Coll Surg Engl ; 102(8): 601-605, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32538115

RESUMO

INTRODUCTION: This study aimed to evaluate the safety and efficacy of paclitaxel-coated balloon compared with conventional plain balloon for the treatment of failing native dialysis access. MATERIALS AND METHODS: This prospective study included 60 patients presenting to the Kasr Alainy Hospitals and Aseer Central Hospital in the period from September 2015 to December 2017 with failing native vascular access. Dilatation with a plain balloon was done in 30 patients (group I) and with a paclitaxel-coated balloon in 30 patients (group II) with either stenosis or occlusion. The majority were outflow lesions, with 20 (66.7 %) patients in group I and 21 (70%) patients in group II. Mean balloon diameter was 7.1mm (± 1.5mm) compared with 6.5mm (± 1.2mm) and length 66mm (± 19.1mm) compared with 54.6mm (± 15.7mm), respectively. Safety endpoint was reported as 30 day's freedom from procedure-related major complications and mortality. Procedural technical success was defined as a residual diameter 30% or less for treated lesions. Target lesion primary patency, circuit primary patency and secondary patency were reported at 3, 6 and 12 months. RESULTS: There were no 30-day procedure-related major complications or mortality in either group. Procedural technical success of 100% was achieved in both groups. Target lesion primary patency, circuit primary patency and secondary patency in group II were better than in group I, especially at 12 months (90% vs 66.7%, 83.3% vs 60% and 96.7% vs 93.3%, respectively). There was a statistically significant difference in target lesion primary patency (p = 0.029) in patients who were treated with paclitaxel-coated balloon angioplasties. CONCLUSION: The paclitaxel-coated balloon proved to be safe and effective, and improved the patency of failing vascular access. Results are comparable with previous studies.


Assuntos
Angioplastia com Balão , Materiais Revestidos Biocompatíveis/uso terapêutico , Paclitaxel , Diálise Renal , Dispositivos de Acesso Vascular/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Complicações Pós-Operatórias , Estudos Prospectivos , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Diálise Renal/métodos , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/prevenção & controle
15.
Exp Hematol ; 84: 1-6.e1, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243995

RESUMO

Sickle cell disease (SCD) is a monogenic disorder estimated to affect more than three million people worldwide. Acute systemic painful vaso-occlusive episode (VOE) is the primary reason for emergency medical care among SCD patients. VOE may also progress to acute chest syndrome (ACS), a type of acute lung injury and one of the primary reasons for mortality among SCD patients. Recently, P-selectin monoclonal antibodies were found to attenuate VOE in SCD patients and lung vaso-occlusion in transgenic humanized SCD mice, highlighting the therapeutic benefit of P-selectin inhibition in SCD. Here, we use quantitative fluorescence intravital lung microscopy (qFILM) to illustrate that tandem P-selectin-glycoprotein ligand-immunoglobulin (TSGL-Ig) fusion molecule containing four P-selectin binding sites, significantly attenuated intravenous (IV) oxyhemoglobin triggered lung vaso-occlusion in SCD mice. These findings highlight the therapeutic potential of TSGL-Ig in preventing VOE and ACS in SCD.


Assuntos
Anemia Falciforme/tratamento farmacológico , Imunoglobulinas/farmacologia , Pneumopatias/tratamento farmacológico , Selectina-P/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Doenças Vasculares/tratamento farmacológico , Anemia Falciforme/genética , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Animais , Feminino , Humanos , Imunoglobulinas/genética , Pneumopatias/genética , Pneumopatias/metabolismo , Pneumopatias/patologia , Masculino , Camundongos , Selectina-P/genética , Ratos , Proteínas Recombinantes de Fusão/genética , Doenças Vasculares/genética , Doenças Vasculares/metabolismo
16.
PLoS One ; 15(2): e0229231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092094

RESUMO

We report 5-year visual and anatomical outcomes after combination therapy of photodynamic therapy (PDT) and intravitreal injection of ranibizumab or aflibercept for polypoidal choroidal vasculopathy (PCV) and predictive factors for visual outcomes at 5-year and time to recurrence. Medical charts were retrospectively reviewed for 43 consecutive eyes with PCV treated with combination therapy of PDT and intravitreal injection of ranibizumab(n = 13) or aflibercept(n = 30) and completed 5-year follow-up. The variants of ARMS2 A69S and CFH I62V were genotyped using TaqMan assay. Best corrected visual acuity (BCVA) significantly improved at 5-year (P = 0.01) with 20% reduction of subfoveal choroidal thickness irrespective of presence or absence of recurrence. Visual improvement was associated with baseline shorter greatest linear dimension (GLD) (P = 1.0×10-4). Mean time to recurrence was 28.6±23.1 months (95% CI: 21.5-35.7, Median:18.0) and time to recurrence was associated with G allele (protective allele) of ARMS2 A69S and GLD (P = 4.0×10-4 and 1.0×10-2, respectively). Multiple regression analysis revealed that time to recurrence extended by 15.5 months when the G allele of ARMS2 A69S increased by one allele (TT: 15.7±17.0, TG: 30.8±23.5, GG: 41.1±22.6 months). The combination therapy resulted in a favorable visual outcome for PCV during 5-year follow-up.


Assuntos
Doenças da Coroide/terapia , Fotoquimioterapia/métodos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Doenças Vasculares/terapia , Idoso , Idoso de 80 Anos ou mais , Doenças da Coroide/tratamento farmacológico , Terapia Combinada/métodos , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Doenças Vasculares/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos
17.
Int Angiol ; 39(2): 118-124, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32052951

RESUMO

Since the publication of the CEAP classification, new research has enriched our knowledge; notably on the heritability of CVD and the genetic and environmental factors involved in this condition, as well as the symptoms apparent within the spectrum of the CEAP clinical classes and the benefits of medical treatment. Using the CEAP classification as a special theme, a symposium with the same title as the present paper was held at the annual meeting of the 2019 European Venous Forum. The lectures presented much valuable information, from which some key points can be extracted. The influence of environmental factors was demonstrated, and the fact that a large amount of information can be obtained from comprehensive history taking. There is robust evidence for heritability. Many candidate genes/loci have been identified, potentially offering new targets for treatment. More research is needed, notably using genome-wide association studies and also on microbiota, which may play a role in CVD through the inflammation pathway. Ruscus + HMC + vitamin C acts by increasing venous and lymphatic tone, protecting microcirculation, and reducing inflammation. It improves quality of life in C0S to C3 CVD patients, while a review of clinical studies and a meta-analysis have confirmed its clinical efficacy across a wide spectrum of CVD clinical classes: C0S, C1S, C2, C3 and C4. It has been awarded a Grade 1A recommendation by the international guidelines.


Assuntos
Ácido Ascórbico/uso terapêutico , Chalconas/uso terapêutico , Hesperidina/uso terapêutico , Extratos Vegetais/uso terapêutico , Ruscus/química , Doenças Vasculares/tratamento farmacológico , Doença Crônica , Hesperidina/análogos & derivados , Humanos , Fitoterapia , Resultado do Tratamento , Doenças Vasculares/classificação , Veias/efeitos dos fármacos
18.
JAMA Netw Open ; 3(2): e1920780, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32031648

RESUMO

Importance: Vascular risk factors are associated with increased risk of Alzheimer disease (AD), but it is unclear whether there is a direct association of these risk factors with AD pathogenesis. Objectives: To assess the associations of vascular risk factors with AD pathogenesis in asymptomatic individuals, and to test whether this association is moderated among individuals who use vascular medications. Design, Setting, and Participants: This cross-sectional study used data from the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) cohort of cognitively unimpaired individuals aged 55 to 82 years with a parental or multiple-sibling history of sporadic AD, who were recruited via advertisement from the greater Montreal, Quebec, Canada, metropolitan area. Participants were enrolled between September 9, 2011, to May, 3, 2017, and stratified by use vs no use of vascular medications. Data were analyzed July 1, 2018, to April 5, 2019. Main Outcomes and Measures: Principal analyses investigated associations of total, high-density lipoprotein, and low-density lipoprotein cholesterol levels, systolic and diastolic blood pressure, pulse pressure, and a combined vascular risk score (measured using the Framingham Coronary Risk Profile) with global ß-amyloid peptide (Aß) and entorhinal tau burden as measured by positron emission tomography (PET). Potential moderating associations of use of vascular medications with these associations were examined. Secondary similar analyses considered cerebrospinal fluid (CSF) Aß1-42 and phosphorylated tau levels. Results: Among 215 participants (mean [SD] age, 62.3 [5.0] years; 161 [74.8%] women), 120 participants underwent PET, including 75 participants (62.5%) who were not using vascular medications, and 162 participants underwent CSF assessment, including 113 participants (69.8%) who were not using vascular medications. There was an overlap of 67 participants who underwent PET and CSF assessment. Interaction analyses showed that among participants not using vascular medications, higher Aß deposition as measured by PET was associated with higher total cholesterol level (ß = -0.002 [SE, 0.001]; P = .02), low-density lipoprotein cholesterol level (ß = -0.002 [SE, 0.001]; P = .006), systolic blood pressure (ß = -0.006 [SE, 0.002]; P = .02), pulse pressure (ß = -0.007 [SE, 0.002]; P = .004), and Framingham Coronary Risk Profile score (ß = -0.038 [SE, 0.011]; P = .001), but such associations were absent in participants who used vascular medications. Interactions were also found between vascular medication use and high-density lipoprotein cholesterol (ß = -3.302 [SE, 1.540]; P = .03), low-density lipoprotein cholesterol (ß = 1.546 [SE, 0.754]; P = .04), and Framingham Coronary Risk Profile score (ß = 23.102 [SE, 10.993]; P = .04) on Aß1-42 burden as measured in CSF. Higher Framingham Coronary Risk Profile scores were associated with reduced tau burden among participants using vascular medications but not among participants not using vascular medications (interaction, ß = -0.010 [SE, 0.005]; P = .046). Conclusions and Relevance: These findings corroborate previously reported associations of vascular risk factors with Aß burden but not tau burden. However, these associations were found only among individuals who were not using vascular medications. These results suggest that medication use or other control of vascular risk factors should be considered in Alzheimer disease prevention trials.


Assuntos
Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fármacos Cardiovasculares/uso terapêutico , Doenças Vasculares/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quebeque , Fatores de Risco , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/psicologia
19.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019237

RESUMO

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment-most likely via a cyclooxygenase-dependent mechanism.


Assuntos
Envelhecimento/patologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Artéria Femoral/efeitos dos fármacos , Veia Femoral/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/química , Doenças Vasculares/tratamento farmacológico , Administração Oral , Animais , Inibidores de Ciclo-Oxigenase/farmacologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Veia Femoral/metabolismo , Veia Femoral/patologia , Masculino , Ratos , Ratos Wistar , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia
20.
Clin Exp Rheumatol ; 38 Suppl 124(2): 69-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969231

RESUMO

OBJECTIVES: Inflammatory fibrosis of aortic lesions promoted by type II macrophages (M2) is one of the most serious incidents in Takayasu's arteritis (TAK), and the currently available therapies can not effectively block the inflammatory fibrosis. Here we explored whether leflunomide (LEF) could improve the fibrosis by down-regulating M2 in TAK. METHODS: Peripheral blood mono-nuclear cells (PBMCs) from 16 TAK patients were treated by leflunomide, and the ratio of M1/M2 macrophages and apoptosis of M2 were detected by flow cytometry. Supernatant levels of cytokines and chemokines secreted by M2 were measured by ELISAs. mRNA expression of profibrotic factors in M2 were analysed by real time PCR. Western blotting was used to analyse the activation of signal transducer activator of transcription (STAT)-6. RESULTS: LEF could inhibit M2 polarisation by curtailing STAT6 phosphorylation. LEF could also promote apoptosis of M2 and reduce the release of M2-derived CCL22 as well as the expression of profibrotic cytokines including CCL22 and TGF-ß in M2. CONCLUSIONS: LEF could potentially reduce vascular fibrosis by down-regulating the number and function of M2, which, eventually, could alleviate inflammatory fibrosis of aortic lesions in TAK patients.


Assuntos
Leflunomida/uso terapêutico , Macrófagos/efeitos dos fármacos , Arterite de Takayasu/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Quimiocina CCL22 , Citocinas , Fibrose/tratamento farmacológico , Humanos , Fator de Transcrição STAT6 , Fator de Crescimento Transformador beta1
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...