RESUMO
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. METHODS: We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. RESULTS: AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels. CONCLUSIONS: Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.
Assuntos
Doença de Fabry , Biomarcadores , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Humanos , Mutação/genética , Estresse Oxidativo , alfa-Galactosidase/genéticaRESUMO
BACKGROUND: Heart rate variability (HRV) decreases in Parkinson's disease (PD) and it can be considered a marker for cardiovascular dysautonomia. The purpose of this pilot study is to evaluate long-term time-domain analysis of HRV of PD patients and compare the results with those of matched healthy individuals. METHODS: Idiopathic PD patients without comorbidity impairing HRV, and age-matched healthy individuals were recruited in a pilot study. A long-term time domain analysis of HRV using 24-h ambulatory ECG was performed. RESULTS: Overall, 18 PD patients fulfilling inclusion criteria completed the evaluation (mean age was 55.6 ± 8.8, disease duration: 5.0 ± 4.7). Mean SCOPA-AUT score was 10.1 ± 7.3. Patients were on Hoehn & Yahr stage 1-2 and mean Levodopa Equivalent Dose (LED) was 311 ± 239.9. Mean of the 5-min standard deviation (SD) of R-R intervals distribution (SDNN) for all 5 min segments of the entire recording (ISDNN) was significantly lower in patients compared to controls. ISDNN was significantly different between Parkinson's disease patients and healthy controls. CONCLUSIONS: In our population characterized by mild to moderate disease severity, time-domain assessment of HRV seemed to be a potential tool to characterize cardiovascular dysautonomia. Decrease of ISDNN in PD may reflect an autonomic derangement extending all day and night long.
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Doenças Cardiovasculares , Frequência Cardíaca/fisiologia , Doença de Parkinson , Idoso , Antiparkinsonianos/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Humanos , Levodopa/uso terapêutico , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Projetos Piloto , Disautonomias Primárias/diagnóstico , Disautonomias Primárias/etiologia , Disautonomias Primárias/fisiopatologiaRESUMO
Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA-KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA-C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA-A-Bw4 and HLA-C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.
Assuntos
Predisposição Genética para Doença , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Hepatite B Crônica/genética , Receptores KIR2DL3/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA). METHOD: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, and interleukin (IL)-6 as markers of immunoinflammatory activation. RESULTS: This study enrolled 53 patients with SpA and 55 control subjects. After adjustment for blood glucose, cholesterol, and triglyceride levels, and systolic (SBP) and diastolic blood pressure (DBP), patients with seronegative SpA showed higher mean PWV and Aix compared to controls. Moreover, in patients with seronegative SpA, we observed higher mean plasma levels of IL-6, IL-1ß, and TNF-α in subjects with mean PWV > 8 m/s in comparison with those with PWV < 8 m/s. Multivariate analysis revealed a significant association between PWV > 8 m/s and male gender, age, diabetes, hypertension, low density lipoprotein cholesterol (LDL-C) > 120 mg/dL, total cholesterol (TC) > 200 mg/dL, coronary artery disease (CAD), microalbuminuria, carotid plaque, and plasma levels of IL-6, IL-1ß, and TNF-α. CONCLUSIONS: These findings emphasize the role of inflammatory variables and metabolic factors in indexes of high arterial stiffness. Thus, an inflammatory-metabolic background may influence the pathogenesis of increased arterial stiffness in seronegative inflammatory arthritis.
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Citocinas/sangue , Índice de Gravidade de Doença , Espondilartrite/sangue , Espondilartrite/fisiopatologia , Rigidez Vascular/fisiologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Onda de Pulso , Fator de Necrose Tumoral alfa/sangueAssuntos
Eletrocardiografia Ambulatorial , Isquemia Miocárdica/diagnóstico , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: This study aimed to evaluate the use of QT intervals, their diagnostic predictive value in patients with syncope and their relationship with syncope severity. METHODS: One hundred and forty nine patients with a diagnosis of syncope were admitted to Internal Medicine departments at the University of Palermo, Italy, between 2006 and 2012, and 140 control subjects hospitalised for other causes were enrolled. QT maximum, QT minimum, QTpeak, QT corrected, QT dispersion and Tpeak-to-Tend interval were compared between two groups. The paper medical records were used for scoring with San Francisco Syncope Rule (SFSR), Evaluation of Guidelines in SYncope Study (EGSYS) score and Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score. RESULTS: Mean QTc (p < 0.0005), mean QTmax (p < 0.0005), mean QTdisp (p < 0.0005), mean QTpeak (p = 0.005) and mean TpTe (p = 0.018) were significantly longer in patients with syncope compared with control subjects. A QTc > 424.8 ms (sensibility: 81.88 - specificity: 57.86) showed the greatest predictive value for diagnosis of syncope. On the EGSYS score and on the OESIL score, QTc was significantly prolonged in high-risk patients compared with low-risk patients. On the San Francisco Syncope Rule, QTc and QTdisp were significantly prolonged in high-risk patients compared with low-risk patients. CONCLUSION: Mean QTc, mean QTdisp, mean TpTe, mean QTmax and mean QTpeak were significantly longer in patients with syncope compared with control subjects. Furthermore, prolonged QTc and QTdisp were associated with major severe syncope according to San Francisco Syncope Rule, EGSYS and OESIL risk scores.
Assuntos
Eletrocardiografia/estatística & dados numéricos , Síncope/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síncope/etiologiaRESUMO
AIMS: Regular exercise demonstrated the ability to provide enormous benefits to many diseases, atherosclerotic-based, degenerative and neoplastic, but also to grant anti-inflammatory actions, assessed by various authors in different populations. Despite of these clear benefits, many patients are unable to attain long-term results through chronic physical activity for different causes. On this basis, the aim of our study was to assess the metabolic and anti-inflammatory effects of a home-based programme of fast walking in patients affected by metabolic syndrome (MS). MATERIALS AND METHODS: We enrolled 176 subjects with MS as stated by ATP III criteria. Patients were invited to walk for 1 h every day 5 days a week for 24 weeks. The walking velocity was required higher than the one retained 'comfortable' by the patient, previously assessed in the run-in visit. Monitoring of physical activity was carried out through an OMRON step counter type Walking Style II. All the subjects enrolled completed the training period. RESULTS: After the 24 weeks of intervention body mass index changed from 31.59 to 29.23 (p < 0.001); mean waist circumference passed from 105.19 to 100.06 cm (p < 0.001); mean fasting glucose changed from 119.76 to 114.32 mg/dl (p < 0.001); for diabetic population (n = 70) mean glicated haemoglobin levels changed from 7.38% to 6.86% (p < 0.001); total cholesterol levels from 192.15 to 185.78 mg/dl (p < 0.001); HDL cholesterol levels raised from 44.03 to 47.63 mg/dl (p < 0.001); triglycerides levels lowered from 148.29 to 135.20 mg/dl (p < 0.001); WBC changed from 7361.08 to 7022.56/mm(3) (p < 0.001); hs-CRP from 0.55 to 0.28 mg/dl (p < 0.001); fibrinogen serum levels lowered from 339.68 to 314.86 mg/dl (p < 0.001). CONCLUSIONS: A long-term home-based programme of aerobic physical activity improves metabolic asset and reduces systemic inflammation in sedentary people.
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Terapia por Exercício/métodos , Síndrome Metabólica/terapia , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Metabolismo Energético , Exercício Físico/fisiologia , Feminino , Serviços de Assistência Domiciliar , Humanos , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Fatores de Risco , Comportamento Sedentário , Circunferência da Cintura , Caminhada/fisiologiaRESUMO
INTRODUCTION: No information exists, to our knowledge, about the possible role of cardiovascular drug administration in the acute phase of ischemic stroke and possible effects on stroke outcome. The aim of our study was to evaluate the relationship between in-hospital treatment with cardiovascular drugs in patients with acute ischemic stroke and some outcome indicators. METHODS AND RESULTS: 1096 subjects enrolled in the GIFA study, who had a main discharge diagnosis of ischemic stroke represent the final sample. Drugs considered for the analysis were the following: ACE-inhibitors (ACEI), angiotensin II receptor blockers (ARBs), statins, calcium-channel-blockers (CCBs), antiplatelet (APL) drugs, antivitamin-k (VKAs), and heparins. As outcome indicators we choose in-hospital mortality, cognitive function evaluated by Hodkinson Abbreviated Mental Test (HAMT), and functional status evaluated by activity daily living (ADL). Indicators of a good outcome were: no in-hospital mortality, HAMT >6 and 0 ADL impaired. Patients with a good outcome showed a higher rate of in-hospital treatment with ACE-inhibitors, calcium-channel blockers and a lower rate of pre-treatment with heparin. CONCLUSIONS: Our study suggests that if a patient with acute ischemic stroke has higher SBP at admission, higher total cholesterol plasma levels, a lower Charlson index and is treated with ACE-inhibitors, calcium channel blockers and antiplatelet drugs, the short term outcome is better in terms of in-hospital mortality and functional indicators such as cognitive and functional performance at discharge.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Atividades Cotidianas , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/fisiopatologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Fármacos Cardiovasculares/efeitos adversos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Comorbidade , Feminino , Avaliação Geriátrica , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Itália/epidemiologia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de TempoRESUMO
AIM: Walking is a very acceptable form of aerobic exercise. Several trials have demonstrated significant benefits of fast walking on the risk factors of cardiovascular disease, particularly for hypertension. Aim of our study was to assess whether physical activity obtained through fast walking might lead to a different reduction of blood pressure levels in hypertensive patients in relation to different circadian profile of blood pressure. METHODS: We have enrolled 84 hypertensive patients, with evidence of stage I hypertension and non-dipper nocturnal profile. All subjects underwent a six weeks physical intervention based on fast walking, three sessions a week. Main outcome measurements were diurnal, nocturnal and 24-h blood pressure levels. RESULTS: After the sixth week of physical exercise there was not any significant change in 24-hour mean systolic blood pressure and diastolic blood pressure ABPM values when compared to baseline (respectively 143.2±5.2 vs. 141±4.4 and 91.4±4.8 vs. 90.1±2.5); also no differences in heart rate have been found. CONCLUSION: In non-dipper hypertensives a light aerobic program of physical activity based on fast walking seems to be less effective to reduce blood pressure values, contrary to what has been observed in dipper ones.
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Pressão Sanguínea , Ritmo Circadiano , Terapia por Exercício , Hipertensão/terapia , Caminhada , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Terapia Combinada , Feminino , Frequência Cardíaca , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
It is well established that physically fit individuals have a reduced risk of developing CVD (cardiovascular disease) and other age-related chronic disorders. Regular exercise is an established therapeutic intervention with an enormous range of benefits. Chronic low-grade systemic inflammation may be involved in atherosclerosis, diabetes and in pathogenesis of several chronic pathological conditions; recent findings confirm that physical activity induces an increase in the systemic levels of a number of cytokines and chemokines with anti-inflammatory properties. The possibility that regular physical exercise exerts anti-inflammation activity, being the interaction between contracting muscle and the other tissues and the circulating cells mediated through signals transmitted by "myokines" produced with muscle contractions. To date the list of myokines includes IL-6, IL-8, and IL-15. During muscle contractions are also released IL-1 receptor antagonis and sTNF-R, molecules that contribute to provide anti-inflammatory actions. Nevertheless discrepancies, analysis of available researches seem to confirm the efficacy of regular physical training as a nonpharmacological therapy having target chronic low-grade inflammation. Given this, physical exercise could be considerate a useful weapon against local vascular and systemic inflammation in atherosclerosis. Several mechanisms explain the positive effect of chronic exercise, nevertheless, these mechanisms do not fully enlighten all pathways by which exercise can decrease inflammation and endothelial dysfunction, and hence modulate the progression of the underlying disease progress.
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Aterosclerose/terapia , Exercício Físico/fisiologia , Inflamação/terapia , Fatores Etários , Animais , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Citocinas/metabolismo , Progressão da Doença , Terapia por Exercício/métodos , Humanos , Inflamação/fisiopatologia , Aptidão Física/fisiologiaRESUMO
The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosterone system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Receptor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflammatory effect of drugs blocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Inflamação/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Inflamação/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. METHODS AND RESULTS: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide+HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5-159.5) pg/ml vs 64 (21-150) pg/ml], BNP [215.5 (80.5-487) pg/ml vs 87 (66-141.5) pg/ml], TNF-α [389.5 (265-615.5) pg/ml vs 231.5 (156-373.5) pg/ml], IL-1ß [8 (7-9) pg/ml vs 4 (3-7) pg/ml], IL-6 [5 (3-7.5) pg/ml vs 3 (2-4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1ß (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups. CONCLUSIONS: Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.