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INTRODUCTION: Reports on patients' satisfaction and preferred characteristics for treatments would be worthwhile when choosing an optimal treatment reflecting patients' perspectives. AIM: To identify the characteristics and treatment patterns of patients with haemophilia A, or their caregivers, in Korea and explore patient preferences and satisfaction with their treatment. METHODS: This cross-sectional, multicentre, observational study was conducted from April 2018 to September 2019 at six nationwide hospitals and three Korea Hemophilia Foundation clinics. Patients aged ≥16 years, or legal caregivers of paediatric patients, who had used factor VIII (FVIII) concentrates for ≥1 month were enrolled. Satisfaction with treatment was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM); preference was evaluated using discrete choice experiment (DCE), with 10 series of two hypothetical treatment options created from D-efficient block design, which varied across five attributes. RESULTS: Overall, 505 patients (mean age 31 years) were enrolled in the study. Patients had received FVIII concentrate for an average of 102.9 months (prophylaxis: 53.5%; on-demand: 22.2%). Mean TSQM scores were 64.6 (effectiveness domain), 97.9 (side effects), 57.1 (convenience) and 66.8 (global satisfaction). The number of vials per injection, and the frequency of drug administration, was significantly associated with treatment satisfaction. According to DCE, simpler treatment options were preferred by patients/caregivers. CONCLUSION: The lowest satisfaction levels were shown in the treatment convenience domain. Patients/parents preferred simpler and easier treatment characteristics. In an attempt to enhance the overall satisfaction of patients and caregivers with treatment, consideration of more convenient characteristics is required in future decisions regarding treatment selection.
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Hemofilia A , Criança , Estudos Transversais , Hemofilia A/tratamento farmacológico , Humanos , Recém-Nascido , Pais , Preferência do Paciente , Satisfação do Paciente , Satisfação PessoalRESUMO
PURPOSE: The increased interspinous distance ratio (ISDR) at the fracture site in plain X-ray is useful as an indicator of injury of the posterior ligament complex in thoracolumbar fractures. METHODS: 154 patients of thoracolumbar junctional fracture (T12, L1, L2) were subjects for this study. The sensitivity, specificity, accuracy of MRI was measured by comparing the surgery findings for the two analysis groups: one in which indeterminate cases were included in the intact group and another in which the indeterminate cases were included in the ruptured group. Sensitivity, specificity, accuracy of ISDR (measured in lateral decubitus X-ray) were measured after dividing patients into 3 groups (110, 120, 130 % increased). RESULTS: MRI's sensitivity, specificity and accuracy were 70.8, 100, and 80.5 %, respectively, when the indeterminate was assumed to have intact PLC. After assuming the indeterminate to have ruptured PLC, sensitivity, specificity and accuracy were 99.1, 52.4, and 85.7 %, respectively. In 53 cases with indeterminate MRI reading, sensitivity, specificity and accuracy were 81.2, 76.2, and 79.2 % %, respectively. CONCLUSION: In this study, in cases where it was difficult to make a diagnosis of the injury in the posterior ligament complex, based on the interspinous distance ratio (ISDR) of 120 % measured in plain X-ray in a lateral decubitus position, the sensitivity was 81.3 %, the specificity was 76.2 %, and the accuracy was 79.2 %. Therefore, measuring the ISDR will be helpful in determining whether surgical treatment is required in patients with thoracolumbar injury.
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Ligamentos Longitudinais/diagnóstico por imagem , Ligamentos Longitudinais/lesões , Vértebras Lombares/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/lesões , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Vértebras Torácicas/lesões , Adulto JovemRESUMO
Caffeine adversely affects endochondral ossification during fetal skeletal growth, and results in increased incidence of delayed and abnormal fetal skeletal development. Chronic caffeine intake also decreases growth hormone secretion. Thus, it is conceivable that caffeine may disrupt bone growth during the peripubertal period. This study aimed to investigate the impact of high-caffeine consumption on bone growth throughout puberty. A total of 51 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg(-1) day(-1) for 4 weeks. After death, the final length and weight of leg bones were measured, and the tibia processed for histomorphometric analysis. Caffeine caused a significant decrease in body mass gain. This was accompanied with proportional decreases in lean body mass and body fat. In addition, bone mass and osteogenic activity in vivo were assessed using dual-energy X-ray absorptiometry and (18) F-NaF positron emission tomography. The results showed significant decreases of bone mass and in vivo osteogenic activity in the caffeine-fed groups. Rats fed with caffeine showed a significantly shorter and lighter tibia and femur and the vertebral column compared with controls. In addition, caffeine does not increase the width of the growth plates (GPs), it slows the rate at which the GP closes due to a slower rate of growth. These results demonstrated that caffeine altered osteogenic activity, leading to delayed peripubertal longitudinal bone growth and maturation. Given that osteogenic cells undergo dynamic changes in metabolic activity and that the pubertal growth spurt is mainly stimulated by growth hormone/insulin-like growth factor-1 and sex steroids during pubertal development, caffeine could suppress ossification by interfering with both physiological changes in hormonal secretion and osteogenic activity during this critical period. Further study will be needed to investigate the cellular/molecular mechanism by which caffeine affects osteogenesis using in vitro experimental models.
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Desenvolvimento Ósseo/efeitos dos fármacos , Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Absorciometria de Fóton , Animais , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Fêmur/efeitos dos fármacos , Lâmina de Crescimento/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacosRESUMO
BACKGROUND: Composite ceramic with polyethylene backing was introduced to enhance the quality of ceramic articulation, but the liner's high rate of ceramic fracture has brought serious concern. In this study, the authors investigated the failure rate of sandwich liner in long-term follow-up patients at single institution. METHODS: In this series, we retrospectively reviewed 134 patients (143 hips), and six patients (6.2%) were found to have liner fracture. They were compared to nonfracture patients to identify the associating factors. General patient characteristics were obtained through review of charts. All patients were implanted with SPH Contact acetabular cup and sandwich liner. Function (Harris hip score) and activity (Devane score) were recorded preoperatively and at final follow-up. Radiologically, inclination and abduction angles were measured for comparison. RESULTS: The study did not show any statistical differences between fracture and nonfracture groups in age, weight or body mass index. Side, type of stem used and radiologic parameters were not also significantly different. The operation had significantly improved function and activity postoperatively in both groups, but no statistical significance was noted between the two groups exception to preoperative Harris hip score. On inspection, retrieved ceramic heads and liners showed substantial metal transfer on their surfaces, and linear wears were evident on the ceramic heads. CONCLUSIONS: Compared to other studies, our series also experienced high rate of sandwich liner fracture. Though its use was generally discontinued, it is worrisome to note that failure rate of the liner will substantially increase over time.
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Acetabuloplastia , Cerâmica/efeitos adversos , Prótese de Quadril , Polietileno/efeitos adversos , Falha de Prótese/etiologia , Adolescente , Adulto , Idoso , Artroplastia de Substituição do Tornozelo/efeitos adversos , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. METHODS: We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. RESULTS: Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). INTERPRETATION: Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.
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Doença de Alzheimer/complicações , Amiloide/metabolismo , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Transtornos Cognitivos/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Angiopatia Amiloide Cerebral , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/patologia , TiazóisRESUMO
The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.
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Isquemia Encefálica/classificação , Encéfalo/patologia , Ventrículos Cerebrais/patologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/patologia , Estudos de Coortes , Demência/classificação , Demência/patologia , Feminino , Humanos , Infarto da Artéria Cerebral Média/classificação , Infarto da Artéria Cerebral Média/patologia , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.
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Doenças Cerebelares/patologia , Disfunção Cognitiva/patologia , Demência Vascular/patologia , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Apraxias/patologia , Atrofia/patologia , Diagnóstico Diferencial , Feminino , Humanos , Leucoencefalopatias/patologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Acidente Vascular Cerebral Lacunar/patologiaRESUMO
The "environmental dependency syndrome" refers to a loss of personal autonomy such that a person's environment almost entirely controls their actions. The goal of this study is to learn if patients with frontotemporal degeneration (FTD) exhibit prolonged TV watching, a behavior which may be a symptom of environmental dependency. We recruited 40 patients with FTD and 48 patients with Alzheimer's disease (AD), and asked these participants' caregivers about TV watching behaviors including total viewing time and channel/show preference, along with other behaviors indicative of environmental dependency. Compared to AD patients, FTD patients watched TV for a longer time. In addition, the patients who watched more TV showed more signs of environmental dependency. Increased TV watching may be a sign of environmental dependency, however further research is needed to explore other hypotheses.
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Demência Frontotemporal/psicologia , Televisão , Idoso , Doença de Alzheimer/psicologia , Meio Ambiente , Feminino , Humanos , MasculinoRESUMO
PURPOSE: Varenicline has demonstrated its safety and efficacy in Western studies including <3% of Asian participants. This prospective multi-center observational study investigated the safety and effectiveness of varenicline in Korean smokers. PATIENTS AND METHODS: Smokers prescribed varenicline for the first time were enrolled from 252 medical institutions. Investigators recorded and graded all adverse events (AEs). To assess the effectiveness of varenicline, the 7-day point prevalence (PP) of smoking cessation was evaluated at the four visits during the 12-week treatment course. Rates of AE incidence and smoking cessation were analyzed using Chi-squared test or Fisher's exact test. This study is registered with ClinicalTrials.gov, number NCT00483002. RESULTS: A total of 3719 and 3700 study subjects were included in the safety and effectiveness analyses, respectively. Overall, 346 (9.3%) subjects experienced 471 AEs: 358 mild, 97 moderate, 9 severe, and 7 serious. The most frequent AEs were nausea (5.1%), dyspepsia (0.8%), abnormal dreams (0.8%), insomnia (0.8%), and headache (0.7%). Among the subjects with AEs, 73 subjects discontinued treatment, of which 68 were due to AE occurrence. The 7-day PP of smoking cessation at weeks 1-2, 3-6, 7-10, and ≥ week 11 were 51.7% (387/749), 59.6% (1740/2922), 73.3% (1114/1520), and 77.0% (1116/1449), respectively (p for trend = 0.023). Comorbidities and allergies were associated with a higher incidence of AEs and lower smoking cessation rate (p < 0.05). Younger subjects, infrequent alcohol drinkers, and lighter smokers showed a higher smoking cessation rate (p < 0.05). CONCLUSION: Varenicline in adult Korean smokers was well tolerated and effective as a smoking cessation aid in routine clinical practice.
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Rhodonoid natural products are found in nature as a scalemic mixture. This interesting phytochemical feature is presumed to originate from a reversible electrocyclic ring opening of the chromene core present in the biogenetic precursors of rhodonoids. Herein, we systematically investigated factors that are responsible for this racemization event. This eventually led us to complete the asymmetric total synthesis of rhodonoids A, C, D, and G.
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Produtos Biológicos , BenzopiranosRESUMO
We present a micro-sphere PDMS film to improve the external quantum efficiency (EQE) in OLEDs. The micro-sphere PDMS film was fabricated with the breath figure (BF) and replica molding process. The polymer template was prepared through stabilization of the water droplets at the polymer/water interface. The micro-sphere PDMS film was fabricated by pouring PDMS on the polymer template. At a 45 mg/mL concentration, the size of the spheres was approximately 12.3 µm and they had the most circular shape, so this condition yielded the best performance, with an improvement of 33% in the EQE and the widest viewing angle ranging from 0° to 50°. As a result, the sphere film's size and distribution seem to play important roles in enhancing the EQE in OLEDs. Furthermore, the flexible sphere film based on polymeric materials could offer an effective, large-scale, mass-produced product and a simple process and approach to achieve high efficiency in flexible OLEDs.
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[Figure: see text].
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Angiotensina II/farmacologia , Fosfolipases A2 do Grupo IV/metabolismo , Hidroxitestosteronas/farmacologia , Hipertensão/induzido quimicamente , Animais , Citocromo P-450 CYP1B1/fisiologia , Citocinas/metabolismo , Dinoprostona/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Tromboxano A2/fisiologiaRESUMO
Mitochondrial oxidative phosphorylation (OXPHOS) has become an attractive target in anti-cancer studies in recent years. In this study, we found that a small molecule phenylbutenoid dimer NMac1 (Nm23-H1 activator 1), (±)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene, a previously identified anti-metastatic agent, has novel anti-proliferative effect only under glucose starvation in metastatic breast cancer cells. NMac1 causes significant activation of AMPK by decreasing ATP synthesis, lowers mitochondrial membrane potential (MMP, ΔΨm), and inhibits oxygen consumption rate (OCR) under glucose starvation. These effects of NMac1 are provoked by a consequence of OXPHOS complex I inhibition. Through the structure-activity relationship (SAR) study of NMac1 derivatives, NMac24 was identified as the most effective compound in anti-proliferation. NMac1 and NMac24 effectively suppress cancer cell proliferation in 3D-spheroid in vivo-like models only under glucose starvation. These results suggest that NMac1 and NMac24 have the potential as anti-cancer agents having cytotoxic effects selectively in glucose restricted cells.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cicloexenos/farmacologia , Nucleosídeo NM23 Difosfato Quinases/efeitos dos fármacos , Estirenos/farmacologia , Trifosfato de Adenosina/biossíntese , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cicloexenos/química , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Ativadores de Enzimas/química , Ativadores de Enzimas/farmacologia , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Glucose/metabolismo , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Estirenos/químicaRESUMO
We examined antithrombotic treatment patterns with clinical characteristics and therapy changes over time in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Using the Health Insurance Review and Assessment service claims database (01JAN2007-30NOV2016) in Korea, we included adult patients with AF and PCI: (1) who underwent PCI with stenting between 01JAN2008 and 30NOV2016; (2) with ≥1 claim for AF (ICD code: I48) (3) with antithrombotics 1 day prior to or at the date of PCI; and (4) with CHADS2-VASc of ≥2. In this study, 7749 patients with AF who underwent PCI, triple therapy, dual therapy, dual antiplatelet therapy (DAPT), and single antiplatelet therapy were prescribed to 24.6%, 3.4%, 60.8%, and 11.0%, respectively. In the triple therapy group, 23.1% persisted with triple therapy for 12 months, whereas the remaining patients switched to a different therapy. In the entire cohort and several subgroups, the median treatment duration of triple therapy was 55-87 days. DAPT use for 12 months was the most common treatment pattern (62.6%) in the DAPT group (median treatment duration, 324-345 days). A significant discrepancy exists between the current guidelines and real-world practice regarding antithrombotic treatment with PCI for patients with AF. Appropriate use of anticoagulants should be emphasized.
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[Figure: see text].
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2-Metoxiestradiol/farmacologia , Angiotensina II/farmacologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Hipertensão/tratamento farmacológico , Ácido 5,8,11,14-Eicosatetrainoico/farmacologia , Animais , Colágeno/metabolismo , Citocromo P-450 CYP1A1/fisiologia , Feminino , Fosfolipases A2 do Grupo IV/genética , Hipertensão/induzido quimicamente , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Prostaglandina E Subtipo EP3/antagonistas & inibidores , Receptores de Prostaglandina E Subtipo EP3/fisiologiaRESUMO
Background We have reported that cytochrome P450 1B1 ( CYP 1B1), expressed in cardiovascular tissues, contributes to angiotensin II -induced vascular smooth muscle cell ( VSMC ) migration and proliferation and development of hypertension in various experimental animal models via generation of reactive oxygen species. This study was conducted to determine the contribution of CYP 1B1 to platelet-derived growth factor-BB-induced VSMC migration and proliferation in vitro and to neointimal growth in vivo. Methods and Results VSMC s isolated from aortas of male Cyp1b1 +/+ and Cyp1b1 -/- mice were used for in vitro experiments. Moreover, carotid arteries of Cyp1b1 +/+ and Cyp1b1 -/- mice were injured with a metal wire to assess neointimal growth after 14 days. Platelet-derived growth factor- BB -induced migration and proliferation and H2O2 production were found to be attenuated in VSMC s from Cyp1b1 -/- mice and in VSMC s of Cyp1b1 +/+ mice treated with 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, a superoxide dismutase and catalase mimetic. In addition, wire injury resulted in neointimal growth, as indicated by increased intimal area, intima/media ratio, and percentage area of restenosis, as well as elastin disorganization and adventitial collagen deposition in carotid arteries of Cyp1b1 +/+ mice, which were minimized in Cyp1b1 -/- mice. Wire injury also increased infiltration of inflammatory and immune cells, as indicated by expression of CD 68+ macrophages and CD 3+ T cells, respectively, in the injured arteries of Cyp1b1 +/+ mice, but not Cyp1b1 -/- mice. Administration of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl attenuated neointimal growth in wire-injured carotid arteries of Cyp1b1 +/+ mice. Conclusions These data suggest that CYP 1B1-dependent oxidative stress contributes to the neointimal growth caused by wire injury of carotid arteries of male mice.
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Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/genética , Citocromo P-450 CYP1B1/genética , Regulação da Expressão Gênica , Neointima/metabolismo , Estresse Oxidativo , Animais , Western Blotting , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Proliferação de Células , Células Cultivadas , Citocromo P-450 CYP1B1/biossíntese , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neointima/patologia , RNA/genéticaRESUMO
BACKGROUND: Recently, we reported that angiotensin II (Ang II)-induced hypertension is mediated by group IV cytosolic phospholipase A2α (cPLA2α) via production of prohypertensive eicosanoids. Since Ang II increases blood pressure (BP) via its action in the subfornical organ (SFO), it led us to investigate the expression and possible contribution of cPLA2α to oxidative stress and development of hypertension in this brain area. METHODS: Adenovirus (Ad)-green fluorescence protein (GFP) cPLA2α short hairpin (sh) RNA (Ad-cPLA2α shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence protein cPLA2α DNA (Ad-cPLA2α DNA) and its control Ad-GFP DNA were transduced into SFO of cPLA2α+/+ and cPLA2α-/- male mice, respectively. Ang II (700 ng/kg/min) was infused for 14 days in these mice, and BP was measured by tail-cuff and radio telemetry. cPLA2 activity, reactive oxygen species production, and endoplasmic reticulum stress were measured in the SFO. RESULTS: Transduction of SFO with Ad-cPLA2α shRNA, but not Ad-Scr shRNA in cPLA2α+/+ mice, minimized expression of cPLA2α, Ang II-induced cPLA2α activity and oxidative stress in the SFO, BP, and cardiac and renal fibrosis. In contrast, Ad-cPLA2α DNA, but not its control Ad-GFP DNA in cPLA2α-/- mice, restored the expression of cPLA2α, and Ang II-induced increase in cPLA2 activity and oxidative stress in the SFO, BP, cardiac, and renal fibrosis. CONCLUSIONS: These data suggest that cPLA2α in the SFO is crucial in mediating Ang II-induced hypertension and associated pathogenesis. Therefore, development of selective cPLA2α inhibitors could be useful in treating hypertension and its pathogenesis.
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Angiotensina II/farmacologia , Encéfalo/enzimologia , Fosfolipases A2 do Grupo IV/fisiologia , Hipertensão/etiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Colágeno/metabolismo , Estresse do Retículo Endoplasmático , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Fosfolipases A2 do Grupo IV/genética , Hipertensão/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. METHODS: This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. RESULTS: The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 µm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). CONCLUSIONS: Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline.
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Retinopatia Diabética/diagnóstico , Fotocoagulação a Laser/métodos , Macula Lutea/inervação , Fibras Nervosas/patologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade VisualRESUMO
Shoulder dislocation is frequently encountered by orthopedists, and closed manipulation is often sufficient to treat the injury in an acute setting. Although most dislocations are diagnosed and managed promptly, there are rare cases that are missed or neglected, leading to a chronically dislocated state of the joint. They are usually irreducible and cause considerable pain and functional disability in most affected patients, prompting the need to find a surgical method to reverse the worsening conditions caused by the dislocated joint. However, there are cases of even greater rarity in which chronic shoulder dislocations are asymptomatic with minimal functional or structural degeneration in the joint. These patients are usually left untreated, and most show good tolerance to their condition without developing disabling symptoms or significant functional loss over time. We report on one such patient who had a chronic shoulder dislocation for more than 2 years without receiving treatment.
Assuntos
Lesões do Manguito Rotador , Luxação do Ombro , Ombro , Acidentes por Quedas , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Amplitude de Movimento Articular , Recidiva , Lesões do Manguito Rotador/diagnóstico , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/fisiopatologia , Ombro/diagnóstico por imagem , Ombro/patologia , Ombro/fisiopatologia , Luxação do Ombro/diagnóstico , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/fisiopatologiaRESUMO
BACKGROUND: Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. OBJECTIVE: The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. METHODS: In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. RESULTS: When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. CONCLUSIONS: Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.