RESUMO
Hyperglycemia alters the function of cerebral endothelial cells from the blood-brain barrier, increasing the risk of cerebrovascular complications during diabetes. This study evaluated the protective effect of polyphenols on inflammatory and permeability markers on bEnd3 cerebral endothelial cells exposed to high glucose concentration. Results show that hyperglycemic condition increased nuclear factor kappa B (NFκB) activity, deregulated the expression of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10) and endothelial-leukocyte adhesion molecule (E-selectin) genes, raised MCP-1 secretion and elevated monocyte adhesion and transendothelial migration. High glucose decreased occludin, claudin-5, zona occludens-1 (ZO-1) and zona occludens-2 (ZO-2) tight junctions production and altered the endothelial permeability. Characterized polyphenolic extracts from the French medicinal plants Antirhea borbonica, Ayapana triplinervis, Dodonaea viscosa and Terminalia bentzoe, and their major polyphenols quercetin, caffeic, chlorogenic and gallic acids limited the pro-inflammatory and permeability alterations caused by high glucose. Peroxisome proliferator-activated receptor gamma (PPARγ) agonist also attenuated these damages while PPARγ antagonist aggravated them, suggesting PPARγ protective action. Interestingly, polyphenols improved PPARγ gene expression lowered by high glucose. Moreover, polyphenols were detected at the intracellular level or membrane-bound to cells, with evidence for breast cancer resistance protein (BCRP) efflux transporter role. Altogether, these findings emphasize the ability of polyphenols to protect cerebral endothelial cells in hyperglycemic condition and their relevance for pharmacological strategies aiming to limit cerebrovascular disorders in diabetes.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Transtornos Cerebrovasculares/prevenção & controle , Hiperglicemia/imunologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Glicemia/metabolismo , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologia , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/imunologia , Linhagem Celular , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/imunologia , Transtornos Cerebrovasculares/patologia , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/imunologia , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , NF-kappa B/metabolismo , PPAR gama/agonistas , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Extratos Vegetais/uso terapêutico , Polifenóis/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/imunologia , Junções Íntimas/patologiaRESUMO
OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality.
Assuntos
Transtornos Cerebrovasculares/mortalidade , Isquemia Miocárdica/mortalidade , Doenças Profissionais/mortalidade , Exposição Ocupacional/efeitos adversos , Exposição à Radiação/efeitos adversos , Urânio , Adulto , Idoso , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Doenças Profissionais/etiologia , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Duoxuekang (DXK, à½à¾²à½à¼à½ à½à½ºà½£à¼à½à½à½ºà¼à½à¾±à½ºà½à¼) is a clinical experience prescription of CuoRu-Cailang, a famous Tibetan medicine master, which has effective advantages in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to investigate the effects of DXK on cerebrovascular function of HH-induced brain injury in mice. MATERIALS AND METHODS: DSC-MR imaging was used to evaluate the effect of DXK on the brain blood perfusion of patients with hypoxic brain injury. HPLC analysis was used to detect the content of salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol in DXK. The model of HH-induced brain injury in mice was established by an animal hypobaric and hypoxic chamber. The BABL/c mice were randomly divided into six groups: control group, model group, Hongjingtian oral liquid group (HOL, 3.3 ml/kg) and DXK groups (0.9, 1.8 and 3.6 g/kg). All mice (except the control group) were intragastrically administrated for a continuous 7 days and put into the animal hypobaric and hypoxic chamber after the last intragastric administration. Hematoxylin-eosin staining was employed to evaluate the pathological changes of brain tissue. Masson and Weigert stainings were used to detect the content of collagen fibers and elastic fibers of brain, respectively. Routine blood test and biochemical kits were used to analyze hematological parameters and oxidative stress indices. Immunofluorescence staining was applied to detect the protein levels of VEGF, CD31/vWF and α-SMA. RESULTS: The results of DSC-MR imaging confirmed that DXK can increased CBV in the left temporal lobe while decreased MTT in the right frontal lobe, right temporal lobe and right occipital lobe of the brain. DXK contains salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol. Compared with the model group, DXK can ameliorate the atrophy and deformation, and increase the number of pyramidal neurons in hippocampal CA3 area and cortical neurocytes. Masson and Weigert stainings results revealed that DXK can significantly increase the content of collagen fibers and elastic fibers in brain. Routine blood test results demonstrated that DXK can dramatically decrease the levels of WBC, MCH and MCHC, while increase RBC, HGB, HCT, MCV and PLT in the blood samples. Biochemical results revealed that DXK can markedly increase SOD, CAT and GSH activities, while decrease MDA activity. Immunofluorescence revealed that DXK can notably increase the protein levels of VEGF, CD31/vWF and α-SMA. CONCLUSIONS: In conclusion, this study proved that DXK can ameliorate HH-induced brain injury by improving brain blood perfusion, increasing the number of collagen and elastic fibers and inhibiting oxidative stress injury. The underlying mechanisms may be involved in maintaining the integrity of cerebrovascular endothelial cells and vascular function. However, further in vivo and in vitro investigations are still needed to elucidate the mechanisms of DXK on regulating cerebral blood vessels.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Medicina Tradicional Tibetana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Actinas/metabolismo , Animais , Circulação Sanguínea/efeitos dos fármacos , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Catalase/metabolismo , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Tecido Elástico/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glutationa/metabolismo , Humanos , Hipóxia/complicações , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/sangue , Extratos Vegetais/uso terapêutico , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismoRESUMO
INTRODUCTION: In young children, excessive cow's milk intake causes iron-deficiency anemia, which is associated with hypercoagulable states. We present a case series of 4 toddlers with excessive milk intake iron-deficiency anemia and cerebral sinovenous thrombosis. METHODS: Retrospective chart review of 4 patients was performed for patients with cerebral sinovenous thrombosis and iron-deficiency anemia secondary to excessive milk intake. Iron-deficiency anemia was defined as hemoglobin <11 mg/dL, mean corpuscular volume <70 fL, and serum ferritin <12 µg/L. Excessive milk intake was defined as consumption of >24 oz daily. Clinical, laboratory, and radiographic features were reviewed. RESULTS: Age ranged from 12 to 24 months. Average hemoglobin, hematocrit, mean corpuscular volume, and ferritin levels were 6.1 g/dL, 22.7 g/dL, 52.7 fL, and 3.2 ng/mL, respectively. Daily milk consumption ranged from 40 to 60 oz. All patients presented with focal neurologic deficits, including seizures in 3. The location of cerebral sinovenous thrombosis varied, and 3 patients had venous infarcts, one of them hemorrhagic. All patients had a limited diet and were described as "picky eaters" by their parents, and only 1 had transitioned of a bottle. All patients were treated with anticoagulation, iron supplementation, and extensive dietary counseling to reduce cow's milk intake. CONCLUSION: Iron-deficiency anemia due to excessive milk intake is an important and preventable etiology of pediatric cerebral sinovenous thrombosis. Focused anticipatory guidance is necessary for at-risk groups to prevent this neurologic emergency.
Assuntos
Anemia Ferropriva/etiologia , Transtornos Cerebrovasculares/etiologia , Leite/efeitos adversos , Trombose/etiologia , Anemia Ferropriva/terapia , Animais , Transfusão de Sangue , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/terapia , Pré-Escolar , Feminino , Heparina/uso terapêutico , Humanos , Lactente , Ferro/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/terapiaRESUMO
OBJECTIVE: Several prior studies have shown lower risk of myocardial infarction (MI) in carotid artery stenting (CAS) compared with carotid endarterectomy. This is likely because the majority of endarterectomies are performed under general anesthesia (GA), whereas CAS is mainly performed under local anesthesia (LA). Performing CAS under GA may reverse its minimally invasive benefits. The aim of this study was to compare the safety profile of CAS-GA with that of CAS-LA. METHODS: A retrospective analysis of the Vascular Quality Initiative database from 2005 to 2017 was performed. Primary outcomes included major adverse cardiac events (MACE), a composite of in-hospital death and MI, and postoperative neurologic events. Multivariable logistic models, and coarsened exact matching were used to evaluate the association between the primary outcomes and anesthesia technique. RESULTS: Of 12,919 CAS cases performed, 2024 (15.7%) were under GA. Comparing CAS-GA with CAS-LA in the overall cohort, CAS-GA had significantly higher crude rates of in-hospital mortality (2.1% vs 0.5%), MI (1.3% vs 0.7%), composite MACE (3.1% vs 1.2%), and ipsilateral stroke (2.3% vs 1.6%). Patients undergoing CAS-GA also had higher rates of dysrhythmia (3.0% vs 2.2%), acute congestive heart failure (1.6% vs 0.7%) and perioperative hypertension (13.2% vs 9.4%), and were more likely to have a length of hospital stay of more than 4 days (prolonged length of stay) (17.6% vs 8.5%) compared with those undergoing CAS-LA. On multivariable analysis, CAS-GA had a 2.3 times higher odds of in-hospital mortality compared with CAS-LA (OR, 2.52; 95% CI, 1.26-5.03), a 1.9 times the odds of MACE (OR, 1.87; 95% CI, 1.15-3.03), and a 2.3 times the odds of acute congestive heart failure (OR, 2.29; 95% CI, 1.26-4.15; all P < .05). In addition, these patients had a 43% higher odds of developing perioperative hypertension (OR, 1.43; 95% CI, 1.09-1.87; P = .01) and almost 2 times the odds of a prolonged length of stay (OR, 1.82; 95% CI, 1.41-2.35; P < .001). The adjusted odds of stroke, dysrhythmia and reperfusion syndrome were not significantly different between the two groups. Additional analysis using coarsened exact matching showed similar results. CONCLUSIONS: In addition to the established increase risk of perioperative stroke/death with CAS compared with carotid endarterectomy, performing it under GA seems to be associated with increased cardiac complications, length of stay, and consequently hospitalization costs. Pending future data from prospective, randomized, controlled trials to validate our findings, there is evidence to suggest that it may be better to perform CAS under LA, especially in medically high-risk patients.
Assuntos
Anestesia Geral , Anestesia Local , Doenças das Artérias Carótidas/terapia , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Anestesia Geral/efeitos adversos , Anestesia Geral/mortalidade , Anestesia Local/efeitos adversos , Anestesia Local/mortalidade , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Cardiopatias/etiologia , Cardiopatias/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares , Circulação Cerebrovascular/efeitos dos fármacos , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/prevenção & controle , Flavonoides/uso terapêutico , Humanos , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêuticoRESUMO
Importance: Macrovascular disease is a leading cause of morbidity and mortality for patients with type 2 diabetes, and medical management, including lifestyle changes, may not be successful at lowering risk. Objective: To investigate the relationship between bariatric surgery and incident macrovascular (coronary artery disease and cerebrovascular diseases) events in patients with severe obesity and type 2 diabetes. Design, Setting, and Participants: In this retrospective, matched cohort study, patients with severe obesity (body mass index ≥35) aged 19 to 79 years with diabetes who underwent bariatric surgery from 2005 to 2011 in 4 integrated health systems in the United States (n = 5301) were matched to 14â¯934 control patients on site, age, sex, body mass index, hemoglobin A1c, insulin use, observed diabetes duration, and prior health care utilization, with follow-up through September 2015. Exposures: Bariatric procedures (76% Roux-en-Y gastric bypass, 17% sleeve gastrectomy, and 7% adjustable gastric banding) were compared with usual care for diabetes. Main Outcomes and Measures: Multivariable-adjusted Cox regression analysis investigated time to incident macrovascular disease (defined as first occurrence of coronary artery disease [acute myocardial infarction, unstable angina, percutaneous coronary intervention, or coronary artery bypass grafting] or cerebrovascular events [ischemic stroke, hemorrhagic stroke, carotid stenting, or carotid endarterectomy]). Secondary outcomes included coronary artery disease and cerebrovascular outcomes separately. Results: Among a combined 20â¯235 surgical and nonsurgical patients, the mean (SD) age was 50 (10) years; 76% of the surgical and 75% of the nonsurgical patients were female; and the baseline mean (SD) body mass index was 44.7 (6.9) and 43.8 (6.7) in the surgical and nonsurgical groups, respectively. At the end of the study period, there were 106 macrovascular events in surgical patients (including 37 cerebrovascular and 78 coronary artery events over a median of 4.7 years; interquartile range, 3.2-6.2 years) and 596 events in the matched control patients (including 227 cerebrovascular and 398 coronary artery events over a median of 4.6 years; interquartile range, 3.1-6.1 years). Bariatric surgery was associated with a lower composite incidence of macrovascular events at 5 years (2.1% in the surgical group vs 4.3% in the nonsurgical group; hazard ratio, 0.60 [95% CI, 0.42-0.86]), as well as a lower incidence of coronary artery disease (1.6% in the surgical group vs 2.8% in the nonsurgical group; hazard ratio, 0.64 [95% CI, 0.42-0.99]). The incidence of cerebrovascular disease was not significantly different between groups at 5 years (0.7% in the surgical group vs 1.7% in the nonsurgical group; hazard ratio, 0.69 [95% CI, 0.38-1.25]). Conclusions and Relevance: In this observational study of patients with type 2 diabetes and severe obesity who underwent surgery, compared with those who did not undergo surgery, bariatric surgery was associated with a lower risk of macrovascular outcomes. The findings require confirmation in randomized clinical trials. Health care professionals should engage patients with severe obesity and type 2 diabetes in a shared decision making conversation about the potential role of bariatric surgery in the prevention of macrovascular events.
Assuntos
Cirurgia Bariátrica , Transtornos Cerebrovasculares/etiologia , Doença das Coronárias/etiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade Mórbida/cirurgia , Adulto , Idoso , Transtornos Cerebrovasculares/prevenção & controle , Doença das Coronárias/prevenção & controle , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Modelos de Riscos Proporcionais , Estudos Retrospectivos , RiscoRESUMO
TITLE: Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.
Assuntos
Bupropiona/efeitos adversos , Artérias Cerebrais/efeitos dos fármacos , Transtornos Cerebrovasculares/etiologia , Transtornos da Cefaleia Primários/etiologia , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias/etiologia , Apraxias/etiologia , Bupropiona/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estenose das Carótidas/complicações , Artérias Cerebrais/diagnóstico por imagem , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/fisiopatologia , Substituição de Medicamentos , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Cetoprofeno/análogos & derivados , Cetoprofeno/uso terapêutico , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neuroimagem , Nimodipina/uso terapêutico , Transtornos da Personalidade/etiologia , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/fisiopatologia , Cefaleia do Tipo Tensional/complicações , Trometamina/uso terapêutico , Vasoconstrição/efeitos dos fármacosRESUMO
OBJECTIVES: The work of public officers involves repeated and long-term exposure to heavy workloads, high job strain and workplace violence, all of which negatively impact physical and mental health. This study aimed to evaluate and compare the incidences of diseases among different categories of public officers in Korea, in order to further understand the health risks associated with these occupations. DESIGN: A cohort study using the National Health Insurance data. PARTICIPANTS: We collated claims data between 2002 and 2014 for 860 221 public officers. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised rates were calculated using the direct standardisation method, and HRs were calculated using the Cox proportional hazard regression models. RESULTS: Overall, we found that police officers and firefighters had a higher incidence of a range of diseases when compared with national and regional government officers (NRG). The most prominent HRs were observed among police officers for angina pectoris (HR: 1.52, 95% CI 1.49 to 1.54), acute myocardial infarction (HR: 1.84, 95% CI 1.77 to 1.92) and cerebrovascular disease (HR: 1.36, 95% CI 1.31 to 1.40). Firefighters were more susceptible to physical ailments and were at a significantly higher risk for traumatic stress disorders (HR: 1.40, 95% CI 1.26 to 1.56) than NRGs. CONCLUSION: Compared withNRGs, police officers had higher HRs for all measured diseases, except for traumatic stress disorders. While firefighters had higher HRs for almost all diseases examined, public education officers had a higher HR for traumatic stress disorders, when compared with NRGs.
Assuntos
Doenças Cardiovasculares/etiologia , Bombeiros , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Polícia , Transtornos de Estresse Traumático/etiologia , Adulto , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Programas Nacionais de Saúde , Doenças Profissionais/epidemiologia , Ocupações , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Transtornos de Estresse Traumático/epidemiologia , Inquéritos e Questionários , Carga de Trabalho , Violência no TrabalhoRESUMO
INTRODUCTION: Sickle cell disease (SCD) is a devastating monogenic disorder that presents as a multisystem illness and affects approximately 100,000 individuals in the United States alone. SCD management largely focuses on primary prevention, symptomatic treatment and targeting of hemoglobin polymerization and red blood cell sickling. Areas covered: This review will discuss the progress of SCD over the last few decades, highlighting some of the clinical (mainly cerebrovascular) and psychosocial challenges of SCD in the United States. In addition, focus will also be made on the evolving science and management of this inherited disease. Expert commentary: Until recently hydroxyurea (HU) has been the only FDA approved therapy for SCD. However, advancing understanding of SCD pathophysiology has led to multiple clinical trials targeting SCD related thrombo-inflammation, abnormal endothelial biology, increased oxidant stress and sickle cell mutation. Yet, despite advancing understanding, available therapies are limited. SCD also imposes great psychosocial challenges for the individual and the affected community, which has previously been under-recognized. This has created a pressing need for complementary adjuvant therapies with repurposed and novel drugs, in addition to the establishment of comprehensive clinics focusing on both the medical treatment and the psychosocial issues associated with SCD.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/genética , Transtornos Cerebrovasculares/etiologia , Hemoglobinas/genética , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/epidemiologia , Antidrepanocíticos/uso terapêutico , Comunicação Celular , Progressão da Doença , Glutamina/metabolismo , Humanos , Hidroxiureia/uso terapêutico , Inflamação/etiologia , Mutação , Neutrófilos/metabolismo , Qualidade de VidaRESUMO
OBJECTIVE: Atrial fibrillation (AF) is an emerging global epidemic associated with significant morbidity and mortality. Whilst other chronic cardiovascular conditions have demonstrated enhanced patient outcomes from coordinated systems of care, the use of this approach in AF is a comparatively new concept. Recent evidence has suggested that the integrated care approach may be of benefit in the AF population, yet has not been widely implemented in routine clinical practice. We sought to undertake a systematic review and meta-analysis to evaluate the impact of integrated care approaches to care delivery in the AF population on outcomes including mortality, hospitalisations, emergency department visits, cerebrovascular events and patient-reported outcomes. METHODS: PubMed, Embase and CINAHL databases were searched until February 2016 to identify papers addressing the impact of integrated care in the AF population. Three studies, with a total study population of 1383, were identified that compared integrated care approaches with usual care in AF populations. RESULTS: Use of this approach was associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80, p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77, p=0.0002) but did not significantly impact on AF-related hospitalisations (OR 0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI 0.48 to 2.09, p=1.00). CONCLUSIONS: The use of the integrated care approach in AF is associated with reduced cardiovascular hospitalisations and all-cause mortality. Further research is needed to identify optimal settings, methods and components of delivering integrated care to the burgeoning AF population.
Assuntos
Fibrilação Atrial/terapia , Transtornos Cerebrovasculares/prevenção & controle , Prestação Integrada de Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Causas de Morte , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/fisiopatologia , Distribuição de Qui-Quadrado , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Resultado do TratamentoAssuntos
Anestesia Geral , Anestesia Local , Doenças das Artérias Carótidas/cirurgia , Transtornos Cerebrovasculares/prevenção & controle , Endarterectomia das Carótidas , Anestesia Geral/efeitos adversos , Anestesia Geral/mortalidade , Anestesia Local/efeitos adversos , Anestesia Local/mortalidade , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Hemodinâmica , Humanos , Medição de Risco , Fatores de Risco , Resultado do TratamentoAssuntos
Anestesia Geral , Anestesia Local , Doenças das Artérias Carótidas/cirurgia , Transtornos Cerebrovasculares/prevenção & controle , Endarterectomia das Carótidas , Anestesia Geral/efeitos adversos , Anestesia Geral/mortalidade , Anestesia Local/efeitos adversos , Anestesia Local/mortalidade , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Hemodinâmica , Humanos , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
Cerebral blood flow dysregulation caused by oxidative stress contributes to adverse neurologic outcome of seizures. A carbon monoxide (CO) donor CORM-A1 has antioxidant and cytoprotective properties. We investigated whether enteral supplements of CORM-A1 can improve cerebrovascular outcome of bicuculline-induced seizures in newborn piglets. CORM-A1 (2 mg/kg) was given to piglets via an oral gastric tube 10 minutes before or 20 minutes after seizure onset. Enteral CORM-A1 elevated CO in periarachnoid cerebrospinal fluid and produced a dilation of pial arterioles. Postictal cerebral vascular responses to endothelium-, astrocyte-, and vascular smooth muscle-dependent vasodilators were tested 48 hours after seizures by intravital microscopy. The postictal responses of pial arterioles to bradykinin, glutamate, the AMPA receptor agonist quisqualic acid, ADP, and heme were greatly reduced, suggesting that seizures cause injury to endothelial and astrocyte components of the neurovascular unit. In contrast, in the two groups of piglets receiving enteral CORM-A1, the postictal cerebral vascular responsiveness to these dilators was improved. Overall, enteral supplements of CORM-A1 before or during seizures offer a novel effective therapeutic option to deliver cytoprotective mediator CO to the brain, reduce injury to endothelial and astrocyte components of cerebral blood flow regulation and to improve the cerebrovascular outcome of neonatal seizures.
Assuntos
Boranos/farmacologia , Monóxido de Carbono , Carbonatos/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/tratamento farmacológico , Suplementos Nutricionais , Convulsões/tratamento farmacológico , Difosfato de Adenosina/farmacologia , Animais , Arteríolas/metabolismo , Arteríolas/patologia , Bradicinina/farmacologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/patologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/farmacologia , Heme/farmacologia , Masculino , Ácido Quisquálico/farmacologia , Convulsões/complicações , Convulsões/metabolismo , Convulsões/patologia , Suínos , Fatores de Tempo , Vasodilatadores/farmacologiaRESUMO
BACKGROUND: Individuals with peripheral arterial disease are at higher risk for cardiovascular events than the general population. While supplementation with omega-3 polyunsaturated fatty acids (PUFA) has been shown to improve vascular function, it remains unclear if supplementation decreases serious clinical outcomes. We conducted a systematic review and meta-analysis to determine whether omega-3 PUFA supplementation reduces the incidence of cardiovascular events and complications in adults with peripheral arterial disease. METHODS: We searched five electronic databases (MEDLINE, EMBASE, CENTRAL, Scopus and the International Clinical Trials Registry Platform) from inception to 6 December 2013 to identify randomized trials of omega-3 PUFA supplementation (from fish or plant oils) that lasted ≥12 weeks in adults with peripheral arterial disease. No language filters were applied. Data on trial design, population characteristics, and health outcomes were extracted. The primary outcome was major adverse cardiac events; secondary outcomes included myocardial infarction, cardiovascular death, stroke, angina, amputation, revascularization procedures, maximum and pain-free walking distance, adverse effects of the intervention, and quality of life. Trial quality was assessed using the Cochrane Risk of Bias tool. RESULTS: Of 741 citations reviewed, we included five trials enrolling 396 individuals. All included trials were of unclear or high risk of bias. There was no evidence of a protective association of omega-3 PUFA supplementation against major adverse cardiac events (pooled risk ratio 0.73, 95% CI 0.22 to 2.41, I2 75%, 2 trials, 288 individuals) or other serious clinical outcomes. Adverse events and compliance were poorly reported. CONCLUSIONS: Our results showed that insufficient evidence exists to suggest a beneficial effect of omega-3 PUFA supplementation in adults with peripheral arterial disease with regard to cardiovascular events and other serious clinical outcomes.
Assuntos
Transtornos Cerebrovasculares/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Cardiopatias/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Distribuição de Qui-Quadrado , Medicina Baseada em Evidências , Cardiopatias/etiologia , Cardiopatias/mortalidade , Humanos , Incidência , Razão de Chances , Doença Arterial Periférica/complicações , Doença Arterial Periférica/mortalidade , Fatores de Proteção , Fatores de Risco , Resultado do TratamentoRESUMO
Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.
Assuntos
Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etiologia , Tálamo/irrigação sanguínea , Algoritmos , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Humanos , Aumento da Imagem/métodos , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin , Tálamo/patologia , Tálamo/fisiopatologiaRESUMO
AIMS: A significant proportion of cardiac surgical patients develop critical post-operative complications. We aimed to investigate the association of pre-operative 25-hydroxyvitamin D (25(OH)D) levels with major cardiac and cerebrovascular events (MACCE) in cardiac surgical patients. METHODS AND RESULTS: From January 2010 to August 2011, we consecutively measured circulating 25(OH)D in 4418 operated patients. Of the study cohort, 38.0% had deficient 25(OH)D values (<30 nmol/L) and additional 32.3% had insufficient values (30-49.9 nmol/L), whereas only 3.1% had values >100 nmol/L. The incidence of MACCE was 11.5%. In multivariable-adjusted logistic regression models, the odds ratio of MACCE at deficient, inadequate, and high 25(OH)D levels was 2.23 [95% confidence interval (CI): 1.31-3.79], 1.73 (95% CI: 1.01-2.96) and 2.34 (95% CI: 1.12-4.89), respectively, compared with 25(OH)D levels of 75-100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay. Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75-100 nmol/L. CONCLUSION: Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE. Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels >100 nmol/L.
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Procedimentos Cirúrgicos Cardíacos , Transtornos Cerebrovasculares/etiologia , Cardiopatias/etiologia , Complicações Pós-Operatórias/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Idoso , Transtornos Cerebrovasculares/sangue , Feminino , Cardiopatias/sangue , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Vitamina D/metabolismoRESUMO
The present study included 161 patients with vibration disease associated with dyscirculatory encephalopathy. It was designed to estimate the degree of cognitive dysfunction and the efficacy of its treatment by physiobalneotherapeutic techniiques including low-frequency pulsed currents in combination with general artificial sodium chloride and iodine bromide baths. In addition, the influence of combined therapy on the clinical course of the disease, results of neuropsychological tests, and cerebral hemodynamics was evaluated.
Assuntos
Balneologia/métodos , Transtornos Cerebrovasculares/terapia , Terapia por Estimulação Elétrica/métodos , Mineração , Exposição Ocupacional/efeitos adversos , Vibração/efeitos adversos , Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Pessoa de Meia-IdadeRESUMO
To date, the most widely used drugs in our anticoagulation clinics are acenocoumarin and warfarin, which belong to the category of vitamin K antagonists (VKA). They have about 70 years of use in the clinic, with proven efficacy for various thrombotic diseases, but also with known problems of variability and dietary and drug interactions. In hospital thromboprophylaxis, the most widely used anticoagulant is enoxaparin, a low molecular weight heparin (LMWH). A new generation of anticoagulants are available, the direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban), with obvious advantages over conventional anticoagulants. This paper summarizes what has been published to date for these new antithrombotics.
Assuntos
Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Benzimidazóis/uso terapêutico , Morfolinas/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Tiofenos/uso terapêutico , beta-Alanina/análogos & derivados , Fibrilação Atrial/complicações , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Dabigatrana , Humanos , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Rivaroxabana , Trombose/etiologia , Trombose/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , beta-Alanina/uso terapêuticoRESUMO
Cervical pain caused by the elongation of the styloid process (Eagle syndrome) is well known to otolaryngologists but is rarely considered by vascular surgeons. We report two patients with cerebrovascular symptoms of Eagle syndrome treated in our medical center in the past year. Case 1: an 80-year-old man with acromegaly presented with dizziness and syncope with neck rotation. The patient was noted to have bilateral elongated styloid processes impinging on the internal carotid arteries. After staged resections of the styloid processes through cervical approaches, the symptoms resolved completely. Case 2: a 57-year-old man presented with acute-onset left-sided neck pain radiating to his head immediately after a vigorous neck massage. Hospital course was complicated by a 15-minute transient ischemic attack resulting in aphasia. Angiography revealed bilateral dissections of his internal carotid arteries, with a dissecting aneurysm on the right. Both injuries were immediately adjacent to the bilateral elongated styloid processes. Despite immediate anticoagulation therapy, he experienced aphasia and right hemiparesis associated with an occlusion of his left carotid artery. He underwent emergent catheter thrombectomy and carotid stent placement, with near-complete resolution of his symptoms. Elongated styloid processes characteristic of Eagle syndrome can result in both temporary impingement and permanent injury to the extracranial carotid arteries. Although rare, Eagle syndrome should be considered in the differential diagnosis in patients with cerebrovascular symptoms, especially those induced by positional change.