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3.
Atheroscler Suppl ; 18: 268-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25936336

RESUMO

AIM: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of familial hypercholesterolemia (FH) and familial combined hypercholesterolemia (FCH), resistant/intolerant to lipid lowering drugs, and hyperlipoproteinemia(a) for which drugs are not available. To assess the effect of LA on the incidence of adverse cardiac or vascular events (ACVE) at the time period of pre-initiation of apheresis and during the LA treatment. METHODS: We collected data of 30 patients (mean age 62 ± 8 years, males 73%), with FH, or FCH and cardiovascular disease on maximally tolerated lipid lowering therapy and LA treatment (median 5 years, interquartile range 3-8 years). Associated hyperlipoproteinemia(a) was present in 16/30 subjects. The LA treatment was performed biweekly as clinically indicated by dextran-sulfate or heparin-induced LDL precipitation apheresis. The ACVE incidence, before and after treatment, was evaluated by statistical analyses. RESULTS: The ACVE incidence occurred before and after the LA treatment inception, were 86 and 15 events respectively. Notably, 6/15 of ACVE were secondary to stent restenosis and 7/15 follow-up events occurred during the first 5 years. The AVCE rates/year were 0.58 and 0.13 respectively (p < 0.001). CONCLUSIONS: Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with FH and FCH and atherosclerotic disease at maximally tolerated lipid lowering therapy.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , Hiperlipoproteinemias/terapia , Hipolipemiantes/uso terapêutico , Lipoproteínas/sangue , Idoso , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Sulfato de Dextrana/uso terapêutico , Feminino , Heparina/uso terapêutico , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/diagnóstico , Hiperlipoproteinemias/epidemiologia , Hipolipemiantes/efeitos adversos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(1): 17-27, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24003531

RESUMO

BACKGROUND: Spiral low-dose computed tomography (LDCT) permits to measure whole-lung volume and density in a single breath-hold. OBJECTIVE: To evaluate the agreement between static lung volumes measured with LDCT and pulmonary function test (PFT) and the correlation between the LDCT volumes and lung density in restrictive lung disease. DESIGN: Patients with Systemic Sclerosis (SSc) with (n = 24) and without (n = 16) pulmonary involvement on sequential thin-section CT and patients with chronic obstructive pulmonary disease (COPD)(n = 29) underwent spirometrically-gated LDCT at 90% and 10% of vital capacity to measure inspiratory and expiratory lung volumes and mean lung attenuation (MLA). Total lung capacity and residual volume were measured the same day of CT. RESULTS: Inspiratory [95% limits of agreement (95% LoA)--43.8% and 39.2%] and expiratory (95% LoA -45.8% and 37.1%) lung volumes measured on LDCT and PFT showed poor agreement in SSc patients with pulmonary involvement, whereas they were in substantial agreement (inspiratory 95% LoA -14.1% and 16.1%; expiratory 95% LoA -13.5% and 23%) in SSc patients without pulmonary involvement and in inspiratory scans only (95% LoA -23.1% and 20.9%) of COPD patients. Inspiratory and expiratory LDCT volumes, MLA and their deltas differentiated both SSc patients with or without pulmonary involvement from COPD patients. LDCT lung volumes and density were not correlated in SSc patients with pulmonary involvement, whereas they did correlate in SSc without pulmonary involvement and in COPD patients. CONCLUSIONS: In restrictive lung disease due to SSc there is poor agreement between static lung volumes measured using LDCT and PFT and the relationship between volume and density values on CT is altered.


Assuntos
Escleroderma Sistêmico/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Testes de Função Respiratória , Espirometria , Adulto Jovem
6.
J Lipid Res ; 53(5): 984-989, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22414482

RESUMO

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects' serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (-69%, -80% and -74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (-27% and -16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.


Assuntos
Remoção de Componentes Sanguíneos , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Transportador 1 de Cassete de Ligação de ATP , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico , Antígenos CD36/metabolismo , Difusão , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Água/metabolismo
8.
J Intern Med ; 257(6): 523-30, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15910556

RESUMO

OBJECTIVES: High levels of plasma high sensitivity C-reactive protein (CRP), sensitive to therapy with statins, have been described in hypercholesterolaemia. In vitro evidence shows that CRP activates the complement system, which, in turn, leads to an increased expression of ICAM-1. Our objectives were to verify whether primary hypercholesterolaemia (PHC) is associated with an upregulation of the inflammatory/immune response, and whether this is sensitive to atorvastatin. METHODS AND RESULTS: We examined the levels of sICAM-1, C3, C4 complement fractions in 48 patients with PHC, with (CAD group) or without (No-CAD group) coronary artery disease (CAD) in comparison with a group of 48 healthy controls. The two patient groups were studied before and after atorvastatin therapy. Both hypercholesterolaemic groups showed higher mean values of sICAM-1, C3 and C4 (P < 0.0001) when compared with the controls. The two groups of patients responded differently to atorvastatin therapy. After 3 months, the C3 levels normalized in both groups of patients (P < 0.02 compared with basal values); C4 was greatly reduced only in the CAD group (P < 0.01). After 12 months of therapy, in CAD group C3 mean levels were still significantly lower than baseline values (P < 0.01); a further decrease in the C4 values (P < 0.05 with respect to levels after 3 months of therapy) and also a substantial reduction in sICAM-1 values (P < 0.001 with respect to basal values) were observed. CONCLUSIONS: High plasma values of C3 and C4 in PHC cluster with high values of sICAM-1, distinguish subjects with CAD and could be used to monitor the anti-inflammatory effect of statin therapy in these patients.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Pirróis/uso terapêutico , Regulação para Cima/imunologia , Adulto , Idoso , Atorvastatina , Biomarcadores/sangue , Complemento C3/análise , Complemento C4/análise , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/imunologia , Feminino , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/imunologia , Imunidade Celular/imunologia , Molécula 1 de Adesão Intercelular/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
9.
Heart ; 90(12): 1438-42, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15547024

RESUMO

OBJECTIVE: To test the working hypothesis that inflammation underlying precocious and severe coronary atherosclerotic disease in familial hypoalphalipoproteinaemia (FH) can be mediated by up regulation of the innate immune response. METHODS AND RESULTS: 52 patients with FH were compared with 52 healthy controls with regard to immune system markers such as C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), C3c, and C4. Patients differed from controls in their significantly lower concentrations of high density lipoprotein cholesterol (30.2 (4.0) v 50.5 (13.6) mg/dl, p < 0.0001) and apolipoprotein A I (113.2 (19.9) v 148.7 (25.1) mg/dl, p < 0.0001) and their higher triglyceride (139.3 (63.2) v 81.4 (41.7) mg/dl, p < 0.0001) and CRP plasma concentrations (median 0.33 mg/dl, range 0.02-4.66 mg/dl v median 0.07 mg/dl, range 0.02-0.85 mg/dl, p < 0.0001), but not in their total cholesterol and low density lipoprotein cholesterol concentrations. Concentrations of protein complement were higher in patients (C3: 150.8 (42.3) v 101.9 (17.4) mg/dl, p < 0.0001; C4: 35.5 (13.6) v 22.8 (6.4) mg/dl, p < 0.0001) and sICAM-1 concentrations were more than double those found in the controls (335.1 (107.5) v 159.5 (78.2) mg/dl, p < 0.0001). CONCLUSIONS: Increased concentrations of sICAM-1, C3c, and C4 co-express with high concentrations of CRP in FH. The lack of signs and symptoms of inflammation in these patients may suggest that the immune response is up regulated as part of the pro-inflammatory mechanisms that are activated in this atherogenic condition.


Assuntos
Proteína C-Reativa , Complemento C3/metabolismo , Complemento C4/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Doença de Tangier/metabolismo , Apolipoproteína A-I/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Complemento C3/análise , Complemento C3c/metabolismo , Complemento C4/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Tangier/sangue , Triglicerídeos/sangue , Regulação para Cima/fisiologia
10.
Neurochem Int ; 36(3): 225-32, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10676857

RESUMO

The stereoselectivity of the serotonin1A (5-HT1A) receptor compound 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity was investigated in membranes from human 5-HT pre-synaptic (raphe nuclei) and post-synaptic (hippocampus and prefrontal cortex) regions of autopsy brains. After sample incubation with agonists and antagonists, results showed that both the racemic mixture of 8-OH-DPAT or its (+) and (-) enantiomers behaved as full agonists in the tested brain regions. Enantiomer potency (EC50, nM) and efficacy (percentage of maximal inhibition, %) values were similar in all regions under investigation. However, some inter and intra-region variations in racemic 8-OH-DPAT potency and efficacy have been observed. In particular, the potency of racemic 8-OH-DPAT was higher in the prefrontal cortex and raphe nuclei than in the hippocampus, where it was in fact lower than either single enantiomers. Agonist effects were competitively reversed by 5-HT1A antagonists, although once again a different profile was revealed in the hippocampus. The data underscores the lack of stereospecificity of 8-OH-DPAT-mediated inhibition of adenylyl cyclase activity in either pre- or post-synaptic human brain regions. Moreover, such results have significant implication, as they support the notion that human 5-HT1A receptors might vary from one brain region to the other.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Inibidores de Adenilil Ciclases , Encéfalo/enzimologia , Colforsina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Sinapses/enzimologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/química , Adenilil Ciclases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/enzimologia , Terminações Pré-Sinápticas/enzimologia , Agonistas do Receptor de Serotonina/química , Estereoisomerismo
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