The influence of ace i/d gene polymorphism in amateur american football athletes in brazil / A influência do polimorfismo genético i/d da eca em atletas amadores de futebol americano no brasil / La influencia del polimorfismo genético i/d de la eca en atletas amateur de fútbol americano en brasil

ABSTRACT Introduction Physical performance depends on a variety of biological and mechanical properties. These different phenotypes are related through the complex interaction between the environment and the individual genetic profile. The hypothesis is that there is a hereditary component that interferes in physical fitness. ACE stands out among the genes that may influence this response. Objectives The objective of this study is to analyze the polymorphism of the ACE gene in American football athletes. Methods: At the end of the study, the sample was composed of 45 male athletes and 72 non-athletes. DNA was extracted from the jugal mucosa. ACE polymorphisms were genotyped through polymerase chain reaction and analyzed using the electrophoresis process. To compare the frequency of genotypes between athletes and the control group, we used the Chi-square test. The association between the frequencies of alleles was verified through the 2X2 contingency tables analyzed using the Chi-square test with Yates correction. The type of study was diagnostic - Investigation of a diagnostic test, level of evidence II. A p-value of ≤0.05 was considered statistically significant for all the analyses. Results The results showed a greater frequency of the D allele in American football athletes when compared with non-athletes, and a significant difference in the genotypic distribution of the athletes being composed of a higher number of the DD genotype as compared to the control group. Conclusion The study provides evidence of the allelic and genotypic influence of ACE polymorphism in amateur American football players in Brazil. Level of evidence II; Investigation of a diagnostic test.

RESUMO Introdução O desempenho físico depende de uma série de propriedades biológicas e mecânicas. Esses diferentes fenótipos são relacionados através da complexa interação entre o ambiente e o perfil genético individual. A hipótese é que existe um componente hereditário que interfere na aptidão física. O gene da ECA destaca-se entre os genes que podem influenciar nessa resposta. Objetivos O objetivo do presente estudo consiste em analisar o polimorfismo genético da ECA em atletas de futebol americano. Métodos: Ao final do estudo, a amostra foi composta por 45 atletas do sexo masculino e 72 não atletas. O DNA foi extraído da mucosa jugal. A genotipagem dos polimorfismos da ECA foi realizada pela reação em cadeia da polimerase e analisada utilizando o processo de eletroforese. Para comparar a frequência dos genótipos entre os atletas e o grupo controle foi utilizado o teste Qui-quadrado. A associação entre as frequências dos alelos foi verificada através das tabelas de contingência 2X2 analisadas usando o teste Qui-quadrado com correção de Yates. O tipo de estudo foi diagnóstico - Investigação de um teste diagnóstico, nível de evidência II. Um valor de p ≤ 0,05 foi considerado estatisticamente significativo para todas as análises. Resultados Os resultados apresentaram uma frequência maior do alelo D nos atletas de futebol americano quando comparados com os não-atletas e uma diferença significativa na distribuição genotípica dos atletas composta por um maior número do genótipo DD confome comparado ao grupo controle. Conclusão O estudo apresenta a evidência da influência alélica e genotípica do polimorfismo da ECA em atletas amadores de futebol americano no Brasil. Nível de evidência II; Investigação de um teste diagnóstico.

RESUMEN Introducción El desempeño físico depende de una serie de propiedades biológicas y mecánicas. Estos diferentes fenotipos son relacionados a través de la interacción compleja entre el ambiente y el perfil genético individual. La hipótesis es que hay un componente hereditario que interfiere en la aptitud física. El gen de la ECA se destaca entre los genes que pueden influir en esta respuesta. Objetivos El objetivo del presente estudio consiste en analizar el polimorfismo genético de la ECA en atletas de fútbol americano. Métodos: Al final del estudio, la muestra estaba compuesta por 45 atletas masculinos y 72 no atletas. El ADN se extrajo de la mucosa yugal. La genotipificación de los polimorfismos de ECA se realizó mediante la reacción en cadena de la polimerasa y se analizó mediante el proceso de electroforesis. Para comparar la frecuencia de los genotipos entre los atletas y el grupo control se utilizó el test Chi-cuadrado. La asociación entre las frecuencias de los alelos se verificó a través de las tablas de contingencia 2X2 analizadas mediante el test de Chi-cuadrado con la corrección de Yates. El tipo de estudio fue diagnóstico-Investigación de un test diagnóstico, nivel de evidencia II. Para todos los análisis, se consideró estadísticamente significativo un valor de p ≤0,05. Resultados Los resultados presentaron una mayor frecuencia del alelo D en los atletas de fútbol americano, en comparación con los no atletas, y una diferencia significativa en la distribución genotípica de los atletas compuesta por un mayor número del genotipo DD, conforme comparado al grupo control. Conclusión El estudio presenta la evidencia de la influencia alélica y genotípica del polimorfismo de ECA en los atletas amateur de fútbol americano en Brasil. Nivel de evidencia II; Investigación de un test diagnóstico.

α-Synuclein Aggregates with ß-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), ß-amyloid1-42 (Aß), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aß or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aß, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aß accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aß or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aß aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding.

"Effects of recombinant human erythropoietin high mimicking abuse doses on oxidative stress processes in rats".

Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30µg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses.

ß2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and Failure.

BACKGROUND/AIMS: The cardiorenal syndrome is a complication in patients hospitalized with chronic heart failure (CHF). The ß2-microglobulin (b2M) level is an index of decreased glomerular filtration rate (GFR), tissue turnover and inflammation. It is an emerging new predictive marker of cardiovascular events and mortality, but its role as a biomarker of cardiorenal remodeling and failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated matrix metalloproteinases, is a biomarker of heart remodeling and failure. We aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in sedentary controls with no tissue remodeling and in veteran athletes with physiological cardiorenal remodeling and athlete's heart (AH). METHODS: We investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners with AH over 50 years. RESULTS: The b2M and TIMP1 levels were higher in CHF patients, and there was a correlation between them (r = 0.5287, p < 0.0095). The b2M level correlated with the severity of cardiorenal impairment: with proBNP (r = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r = 0.83, p < 0.0001). b2M was also correlated with TIMP1 in AH subjects (r = 0.7548, p < 0.0001) but not in controls. This correlation was independent from GFR in both CHF patients and sedentary controls. CONCLUSIONS: In CHF patients, the plasma levels of b2M and TIMP1 were linked together and correlated with the severity of cardiorenal failure. Moreover, a strong correlation between b2M and TIMP1 characterized cardiovascular remodeling not only in CHF patients but also in AH subjects. These findings suggest that clinicians should use b2M and TIMP1 as associated biomarkers of cardiorenal remodeling and failure.

It's not all in your car: functional and structural correlates of exceptional driving skills in professional racers.

Driving is a complex behavior that requires the integration of multiple cognitive functions. While many studies have investigated brain activity related to driving simulation under distinct conditions, little is known about the brain morphological and functional architecture in professional competitive driving, which requires exceptional motor and navigational skills. Here, 11 professional racing-car drivers and 11 "naïve" volunteers underwent both structural and functional brain magnetic resonance imaging (MRI) scans. Subjects were presented with short movies depicting a Formula One car racing in four different official circuits. Brain activity was assessed in terms of regional response, using an Inter-Subject Correlation (ISC) approach, and regional interactions by mean of functional connectivity. In addition, voxel-based morphometry (VBM) was used to identify specific structural differences between the two groups and potential interactions with functional differences detected by the ISC analysis. Relative to non-experienced drivers, professional drivers showed a more consistent recruitment of motor control and spatial navigation devoted areas, including premotor/motor cortex, striatum, anterior, and posterior cingulate cortex and retrosplenial cortex, precuneus, middle temporal cortex, and parahippocampus. Moreover, some of these brain regions, including the retrosplenial cortex, also had an increased gray matter density in professional car drivers. Furthermore, the retrosplenial cortex, which has been previously associated with the storage of observer-independent spatial maps, revealed a specific correlation with the individual driver's success in official competitions. These findings indicate that the brain functional and structural organization in highly trained racing-car drivers differs from that of subjects with an ordinary driving experience, suggesting that specific anatomo-functional changes may subtend the attainment of exceptional driving performance.

Cardiac involvement in chronic progressive external ophthalmoplegia.

Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients.

How skill expertise shapes the brain functional architecture: an fMRI study of visuo-spatial and motor processing in professional racing-car and naïve drivers.

The present study was designed to investigate the brain functional architecture that subserves visuo-spatial and motor processing in highly skilled individuals. By using functional magnetic resonance imaging (fMRI), we measured brain activity while eleven Formula racing-car drivers and eleven 'naïve' volunteers performed a motor reaction and a visuo-spatial task. Tasks were set at a relatively low level of difficulty such to ensure a similar performance in the two groups and thus avoid any potential confounding effects on brain activity due to discrepancies in task execution. The brain functional organization was analyzed in terms of regional brain response, inter-regional interactions and blood oxygen level dependent (BOLD) signal variability. While performance levels were equal in the two groups, as compared to naïve drivers, professional drivers showed a smaller volume recruitment of task-related regions, stronger connections among task-related areas, and an increased information integration as reflected by a higher signal temporal variability. In conclusion, our results demonstrate that, as compared to naïve subjects, the brain functional architecture sustaining visuo-motor processing in professional racing-car drivers, trained to perform at the highest levels under extremely demanding conditions, undergoes both 'quantitative' and 'qualitative' modifications that are evident even when the brain is engaged in relatively simple, non-demanding tasks. These results provide novel evidence in favor of an increased 'neural efficiency' in the brain of highly skilled individuals.

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people.

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0.01) and frequency domain (HF and LF/HF ratio, p < 0.01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0.01). In the whole population SDNN was inversely related to IMT, respectively (r = -0.60 and r = -0.58, p < 0.0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes.

Assessment of skin microvascular endothelial function in patients with acute unilateral vestibular syndrome.

Abnormalities in labyrinth vasculature, resulting in labyrinth ischemia may be responsible for acute unilateral vestibular syndrome (AVS). However, since no tools for the study of the labyrinth microvasculature are available in clinical settings, labyrinth microvascular abnormalities in AVS patients (AVS-pts) can only be hypothesized on the basis of the their cardiovascular risk profile. Considering that skin microcirculation may mirror vascular function in other body districts, we examined skin endothelial function in 20AVS-pts and in 20 healthy control subjects (CS), with the aim of predicting labyrinth microvascular abnormalities in the same AVS-pts, potentially involved in the pathogenesis of their AVS. AVS-pts and CS underwent laser-Doppler flowmetry measurement of the skin forearm vasodilator response (SVR) to iontophoresis of the endothelial-dependent vasodilator acetylcholine (ACh) and to the endothelial-independent vasodilator sodium nitroprusside (SNP). SVR to ACh was significantly lower than to SNP in AVS patients (p < 0.005, ANOVA for repeated measures), consistent with skin endothelial dysfunction, while no significant differences in SVR between ACh and SNP were observed in CS. Accordingly with an arbitrary cut-off of 30% or greater reduction in SVR to ACh compared to SNP, endothelial dysfunction was found in 4 (20%) of CS, and in 14 (70%) of AVS-pts (6 with associated co-morbidities potentially responsible for endothelial dysfunction, and 8 without these co-morbodities). This study shows that the investigation of skin endothelial function in AVS-pts may be helpful in identifying AVS-pts in whom an ischemic origin of AVS might be more probable, in spite of their low cardiovascular risk profile.

Study of skin vasomotion in type 1 diabetic patients and of its possible relationship with clinical and laboratory variables.

Vascular oscillation (vasomotion) occurs in the microcirculation and is thought to be a significant contributor to tissue perfusion. Our aim was to assess skin vasomotion (SV) of type 1 diabetic patients (T1D-pts) and its relationship with clinical or laboratory variables of the studied T1D-pts. Forearm endothelial-, sympathetic- and myogenic-dependent SV were assessed basally and after 3 min of forearm ischemia in 40 T1D-pts and 50 healthy controls, by spectral analysis of laser-Doppler (LD) signal at the frequency ranges of 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz, respectively. Post-ischemic per cent increase (PI%-increase) in power spectral density (PSD) of skin endothelial- and sympathetic-dependent VS was significantly reduced in T1D-pts compared to controls (p < 0.0005, p < 0.0001, respectively). Linear regression analysis showed a significant positive relationship between PI%-increase of endothelial-dependent SV and heart rate variation during laying-standing test (R = 0.65, p = 0.00001), and a negative relationship between PI%-increase in PSD of skin LD signal 0.009-1.6 Hz spectrum and glycated haemoglobin serum levels (R = 0.44, p = 0.0036) in T1D-pts. These results are consistent with reduced skin endothelial- and sympathetic-dependent stimulated SV and with relationships between some clinical or laboratory variables and SV parameters in the T1D-pts studied.

Peripheral microvascular dysfunction as an independent predictor of atherosclerotic damage in type 1 diabetes patients: a preliminary study.

It has been recently hypothesized that peripheral microvascular dysfunction may contribute to atherosclerotic damage (AD) in diabetic patients. In order to test this hypothesis, we assessed forearm skin post-occlusive reactive hyperaemia (skin-PORH), an index of peripheral microvascular function, using laser-Doppler flowmetry, in 40 type 1 diabetes patients (T1D-pts), aged 49 ± 11 years, with no known cardiovascular complications, and in 50 age and sex-matched healthy control subjects (CS). T1D-pts also underwent carotid arteries ultrasound scanning (Ca-US) and ankle-brachial index (ABI) measurement. An arbitrary index of AD (AD-index), ranging from "0" (normal ABI, normal Ca-US) to "3" (abnormal ABI, one or more plaques at the Ca-US), was determined in T1D-pts. Linear and multiple regression analyses were performed to identify independent predictors of AD in T1D-pts. T1D-pts had a lower skin-PORH compared with CS (p = 0.015). In T1D-pts AD-index resulted to be negatively related with skin-PORH (R = 0.44; p < 0.005) or deep-breathing test (DBT) (R = 0.53; p < 0.0005), and positively related with systolic arterial pressure (R = 0.31; p < 0.05), microalbuminuria (R = 0.46; p < 0.005), patients' age (R = 0.51; p < 0.001) and diabetes duration (R = 0.39; p < 0.05). At the multiple regression analysis skin-PORH (R = 0.36; p < 0.005), patients' age R = 0.24; p < 0.05) and DBT (R = 0.4 - p < 0.005) resulted to be independent predictors of AD-index in T1D-pts. These preliminary findings support the hypothesis that peripheral microvascular dysfunction may contribute to AD in T1D-pts.

Age related cardiovascular dysfunction and effects of physical activity.

The aim of the present article is to review the principal pathogenetic pathways of age-related cardiovascular changes and the positive effects of physical activity on these changes as well as on related cardiovascular dysfunction. The ageing mechanisms reviewed have been grouped into reduced tolerance of oxidative stress, loss of cardiac stem cells, cardiovascular remodeling and impairment of neurovegetative control. New pathogenetic conditions and their tests are described (sirtuines, telomere length, heart rate variability). Age related cardiovascular changes predispose the individual to arterial hypertension, heart failure and arrythmia. A broad spectrum of tests are available to indentify and monitor the emerging cardiovascular dysfunction. Physical activity influences all age related cardiovascular mechanisms, improves cardiovascular function and even, at moderate intensity can reduce mortality and heart attack risk. It is likely that the translation of laboratory studies to humans will improve understanding and stimulate the use of physical activity to benefit cardiovascular patients.

Skin vasodilator function and vasomotion in patients with morbid obesity: effects of gastric bypass surgery.

Obesity-associated microvascular dysfunction (MVD) involves different body tissues, including skin, and concurs to increased cardiovascular risk in obese patients (Ob-P). Generalized improvement of MVD is an important goal in obesity treatment. Since skin MVD mirrors generalized systemic MVD, skin microvascular investigation in prospective studies in Ob-P may surrogate microvascular investigation in organs more important for cardiovascular risk of the studied patients. In this prospective study, we measured forearm skin post-occlusive reactive hyperaemia (PORH), as percentage flow increase from baseline, and skin vasomotion in 37 Ob-P before Roux-en-Y gastric bypass (RYGB), and in 24 of them about 1 year after RYGB, using laser Doppler flowmetry (LDF). The spectral contribution of skin LDF signal oscillations in the frequency intervals of 0.01-0.02 Hz, 0.02-0.06 Hz, and 0.06-0.2 Hz--corresponding to endothelial-, sympathetic-, and myogenic-dependent vasomotion, respectively, was measured by means of spectral Fourier analysis. The same measurements were also performed in 28 healthy, lean subjects (HLS). Before RYGB, Ob-P had a significant reduction in PORH and in the all vasomotion parameters investigated, compared with HLS. After RYGB, Ob-P who completed the follow-up, had a significant weight loss (∼40 kg on average), together with a full normalisation in PORH and in vasomotion parameters, regardless of diabetes status. Surgically induced sustained weight loss resulted in full normalisation of skin microvascolar function in Ob-P about 1 year after RYGB. This result suggests a beneficial effect of sustained weight loss on generalized MVD of the studied Ob-P.

Cardiovascular complications in patients with pheochromocytoma: a mini-review.

Phaeochromocytomas are rare neuroendocrine tumours secreting high levels of catecholamines, able to exert serious metabolic and cardiovascular effects. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines, especially noradrenaline, the main transmitter released from sympathetic nerve terminals. Hypertension, tachycardia, pallor, headache and anxiety, usually dominate the clinical presentation. Occasionally, patients with predominantly epinephrine-secreting tumours present hypotension or even shock. Other cardiovascular complications of pheochromocytoma include ischaemic heart disease, acute myocardial infarction, cardiac arrhythmias, heart failure due to toxic cardiomyopathy, or pulmonary edema. Catecholamines have been shown to influence the extracellular matrix with collagen deposition and subsequent fibrosis in the arterial wall and in the myocardium. These morphofunctional changes of the myocardium and of arterial wall can be emphasized by ultrasound imaging. Indeed, ultrasound imaging of the myocardium and arterial wall not only identifies wall thickness but also contains information on texture that may be revealed by acoustic tissue characterization. The latter can be quantified through videodensitometric analysis of echographic images or through ultrasonic integrated backscatter signal analysis. This paper reviews cardiovascular complications in patients with pheochromocytoma and utility of the new ultrasound technique as backscatter signal. It is useful for evaluating preclinical pathological morphofunctional changes of the myocardium and arterial wall, characterized by increased collagen content in pheochromocytoma patients. The recognition of early catecholamine-induced alterations in patients with pheochromocytoma, is important to prevent at least morbidity and mortality, before surgical treatment.

Effect of telmisartan on QT interval variability and autonomic control in hypertensive patients with left ventricular hypertrophy.

OBJECTIVES: The aim of the study was to examine the effect of the antihypertensive AT1 receptors antagonist telmisartan on cardiovascular autonomic function and QT dispersion in hypertensive patients with LVH. METHODS: Twenty-five patients (18 males and seven women, mean age 49.8±5.2 years) with mild essential arterial hypertension and LVH were compared with 25 age-matched healthy controls. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements and 24h ambulatory ECG monitoring for measurement of heart rate variability. The ECG, 24h ambulatory ECG, and echocardiogram were repeated after eight weeks of treatment. RESULTS: At baseline, hypertensive patients showed QT dispersion (p<0.001) and QTc dispersion (p<0.001) significantly higher than control subjects. An eight-week telmisartan treatment significantly reduced blood pressure (p<0.0001), without significant change in left ventricular mass. Telmisartan-based treatment induced an increased vagal activity without significant change of sympathetic activity and a reduction of QT dispersion (p<0.001) and QTc dispersion (p<0.001). CONCLUSIONS: These data suggest that therapy with telmisartan significantly improves the sympathovagal balance increasing parasympathetic activity, and cardiac electrical stability reducing the heterogeneity of ventricular repolarization in hypertensive subjects. These effects could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.

Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation.

Mitochondrial diseases are due to impairment of the mitochondrial respiratory chain. A plausible pathogenic mechanism leading to cellular dysfunction and phenotypic expression is oxidative stress, but there are surprisingly few clinical studies on this subject. Glutathione (GSH) deficiency has been reported in mitochondrial diseases, and the biosynthesis of glutathione depends on cysteine availability. We have examined oxidative stress biomarkers [advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP)] in blood samples from 27 patients and 42 controls. AOPP levels were greater in patients than in controls (P value <0.00001). Therefore, we performed a double-blind cross-over study to evaluate if 30-day supplementation with a whey-based cysteine donor could modify these markers, reduce lactate concentration during aerobic exercise, or enhance muscular strength and quality of life. Treatment did not modify lactate concentration, clinical scale (MRC) or quality of life (SF-36), but significantly reduced oxidative stress levels. Our findings reinforce the notions that in mitochondrial diseases oxidative stress is important and can be reduced by administration of a cysteine donor. Oxidative stress biomarkers may be useful to detect redox imbalance in mitochondrial diseases and to provide non-invasive tools to monitor disease status.

High circulating levels of N-terminal pro-brain natriuretic peptide and interleukin 6 in patients with mixed cryoglobulinemia.

Many patients with mixed cryoglobulinemia and chronic HCV infection experience symptoms, such as dyspnea, which sometimes do not seem to indicate the involvement of the liver but rather the symptoms of heart failure. To our knowledge, there has been no other study evaluating the serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and Interleukin 6 (IL-6) in such patients. Serum NTproBNP and IL-6 were assayed in 54 patients with mixed cryoglobulinemia and chronic HCV infection, and in 54 sex- and age-matched controls. Cryoglobulinemic-patients showed significantly higher mean NTproBNP and IL-6 levels than the controls (P = 0.005). By defining a high NTproBNP level as a value higher than 125 pg/ml (the single cut-off point for patients under 75 years of age), 30% of patients with mixed cryoglobulinemia and chronic HCV infection and 7% of controls had high NTproBNP (chi-square; P < 0.003). With a cut-off point of 300 pg/ml (used to rule out heart failure in patients under 75 years of age), 5/49 patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P < 0.04). With a cut-off point of 900 pg/ml (used for including heart failure in patients aged between 50 and 75, such as the patients in this study) 3/51 of patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P = 0.07). The study revealed high levels of circulating NTproBNP and IL-6 in patients with mixed cryoglobulinemia and chronic HCV infection. The increase in NTproBNP could indicate the presence of a subclinical cardiac dysfunction.

In vitro and in vivo study on the antioxidant activity of dexrazoxane.

OBJECTIVES: The iron chelator dexrazoxane has been shown to significantly reduce anthracycline-induced cardiac toxicity in several randomized controlled studies. Aim of the present study was to assess the in vitro and in vivo antioxidant effects of dexrazoxane. METHODS: The in vitro antioxidant activity of dexrazoxane as its total oxyradical scavenging capacity (TOSC) was assessed and compared to that of some classic antioxidants such as reduced glutathione (GSH), uric acid and trolox. The plasma antioxidant activity of 20 newly-diagnosed non-Hodgkin lymphoma (NHL) patients scheduled to receive anthracycline-containing chemotherapy (ProMECE-CytaBOM) was also evaluated. Results were expressed as TOSC units. RESULTS: Dexrazoxane exhibited an in vitro scavenging capacity towards hydroxyl radicals 320% higher than that of GSH (p<0.00001), 20% higher than that of uric acid (p<0.001), and 100% higher than that of trolox (p<0.001). In the clinical study, ProMECE-CytaBOM infusion significantly reduced plasma TOSC in NHL patients (p=0.0001). Dexrazoxane supplementation was able to restore plasma antioxidant activity in two hours from the end of the ProMECE-CytaBOM infusion. CONCLUSIONS: Dexrazoxane has in vitro antioxidant capacity. In vivo, it is able to reduce the epirubicin-induced free radical production. The intrinsic antioxidant effect of this compound could explain the reduction of the anthracyclines-induced toxicity in those patients treated with dexrazoxane supplementation.

Acute and subacute effect of rheopheresis on microvascular endothelial function in patients suffering from age-related macular degeneration.

This study was performed on seven patients affected by the atrophic form of age-related macular degeneration (AF-ARMD). The patients under investigation belonged to a larger study aimed at evaluating the efficacy of rheopheresis treatment (RT) on the visual function of AF-ARMD patients. Following the protocol of the larger study, patients received RT twice a week, every two weeks, for a total of ten treatments, as well as high-dose supplementation with zinc and vitamins A, E and beta-carotene. Recruited patients underwent skin laser Doppler flowmetry coupled with skin iontophoresis of the endothelium-dependent vasodilator acetylcholine (ACh) and a test of skin post-ischemic reactive hyperemia, before and after the first RT (time 1: all seven patients) and the fifth RT (time 2: six patients). A significantly higher absolute (anova for repeated measures) and relative (percentage change from the baseline) skin blood flux response (SBFR) to ACh iontophoresis was observed after RT, compared to before RT at time 1 (679 +/- 43% and 436 +/- 78%, respectively; P < 0.05), as well as before RT at time 2 compared to before RT at time 1 (683 +/- 74% and 436 +/- 78%, respectively; P < 0.05). Absolute and relative SBFR to ischemia did not differ either after RT compared to before RT at time 1, or before RT at time 2 compared to before RT at time 1. These findings are consistent with an acute and subacute beneficial effect of RT on skin microvascular endothelial function in the studied AF-ARMD patients.

High circulating N-terminal pro-brain natriuretic peptide and tumor necrosis factor-alpha in mixed cryoglobulinemia.

AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor alpha (TNF-alpha) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV). METHODS: Serum NTproBNP and TNF-alpha levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls. RESULTS: Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-alpha levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (c2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (c2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (c2, P = 0.08). CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-alpha in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.