Introduction
Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in ...young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS).
Design
NUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14.
Setting/participants
98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD.
Intervention
The intervention strategy was the assignment of a LGIMD or a control diet.
Outcome measures
The main outcome measure was NAFLD score, defined by LUS.
Results
After randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed.
Conclusions
LGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.
Pulmonary arterial hypertension (PAH) is a heart failure syndrome characterized by right ventricular (RV) to pulmonary circulation uncoupling, counteracted by the sympathetic nervous system ...activation leading to β1-receptors and α-myosin heavy chain downregulation, downregulation of the sarcoplasmic reticulum Ca2+ATPase, and β-myosin heavy chain upregulation.
Increased ventilation (VE) associated with VE inefficiency further characterizes PAH, as shown by an elevated VE versus carbon dioxide relationship slope during exercise, reflecting a specific behavior with progressive increase of dead space (VD) VE. The sympathetic system interacts with chemoreceptor-mediated VE control with increased VD leading to VE/perfusion mismatch.
Growing evidence in the experimental models shows beneficial effects of different adrenoreceptor blockers on both right heart and pulmonary artery morphology and function. These effects can significantly change among β-blockers according to their different pharmacokinetic and pharmacodynamic profiles.
Since the first observation in the clinical setting, showing improvement associated with β-blocker withdraw in PAH patients, recent studies suggest that the effects of β-blockers in PAH might be related to the β1-adrenergic receptors selectivity and α1– and β3-related ancillary properties.
While in the advanced stages of PAH β-blockers may result deleterious as counteract the compensatory adrenergic-mediated effects of low cardiac output, in the early stages the modulation of the adrenergic system could ultimately improve VE efficiency and promote beneficial effects on heart failure gene expression and RV remodeling, particularly β1-selective blockers and those associated with α- or β3-activities.
At present, all the above are physiologically sound but clinically unproven suggestions, and need to be tested in future randomized controlled trials.
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Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in systemic sclerosis (SSc). Lung microvascular changes can play a role in the ...pathogenesis of idiopathic PAH (IPAH) also. The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with IPAH and to evaluate the differences in capillary nailfold changes between patients with IPAH and patients with SSc with and without PAH.
39 SSc patients (19 with PAH – SSc-PAH and 20 without – SSc-noPAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart catheterization. Nailfold videocapillaroscopy was performed (NVC) in all recruited subjects; capillary quantitative parameters (loops length and width, capillary density, neoangiogenesis) were evaluated and a semiquantitative scoring was used (normal, minor or major abnormalities for healthy controls and IPAH subjects and specific patterns – early, active and late – for SSc subjects) to define microvascular alterations.
The presence of capillaroscopic abnormalities was detected in 38,1% subjects with IPAH; particularly, compared to healthy controls, capillary density was significantly lower (7,5±1,65loops/mm vs 9±1,37loops/mm p<0,05) and mean capillary width was significantly higher (21±13μm vs 17±3μm p<0,05). A more severe NVC pattern (active/late) was described. SSc-PAH patients compared to SSc-noPAH patients (73,2% vs 50% respectively, p<0,05), with a significantly lower capillary density (5,64±1,9loops/mm vs 6,5±1,3loops/mm p<0,05) and a significantly higher capillary width (55±7μm vs 35±8μm - p<0,05) and mean number of neoangiogenesis (N/mm) (1±0,33 vs 0,2±0,22 respectively p<0,05).
These data, beyond to confirm the role of microvascular damage in SSc-related PAH, support the hypothesis of systemic microvascular involvement in IPAH also, which can be detected by NVC, although further studies are needed to establish whether the changes in the systemic microcirculation are causal or consequential to PAH.
Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) ...aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty‐four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end‐tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak PETCO2 < median and VE/VCO2 slope > median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 − 0.0925 × peak VO2 − 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild‐to‐moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.
Neuronal and glial sodium-dependent transporters are crucial for the control of extracellular glutamate levels in the CNS. The regulation of these transporters is relatively unexplored, but the ...activity of other transporters is regulated by protein kinase C (PKC)- and phosphatidylinositol 3-kinase (PI3K)-mediated trafficking to and from the cell surface. In the present study the C6 glioma cell line was used as a model system that endogenously expresses the excitatory amino acid carrier 1 (EAAC1) subtype of neuronal glutamate transporter. As previously observed, phorbol 12-myristate 13-acetate (PMA) caused an 80% increase in transporter activity within minutes that cannot be attributed to the synthesis of new transporters. This increase in activity correlated with an increase in cell surface expression of EAAC1 as measured by using a membrane-impermeant biotinylation reagent. Both effects of PMA were blocked by the PKC inhibitor bisindolylmaleimide II (Bis II). The putative PI3K inhibitor, wortmannin, decreased L-3H-glutamate uptake activity by >50% within minutes. Wortmannin decreased the Vmax of L-3H-glutamate and D-3H-aspartate transport, but it did not affect Na+-dependent 3H-glycine transport. Wortmannin also decreased cell surface expression of EAAC1. Although wortmannin did not block the effects of PMA on activity, it prevented the PMA-induced increase in cell surface expression. This trafficking of EAAC1 also was examined with immunofluorescent confocal microscopy, which supported the biotinylation studies and also revealed a clustering of EAAC1 at cell surface after treatment with PMA. These studies suggest that the trafficking of the neuronal glutamate transporter EAAC1 is regulated by two independent signaling pathways and also may suggest a novel endogenous protective mechanism to limit glutamate-induced excitotoxicity.
We examined the relationship between moderate obesity and glucose metabolism, insulin sensitivity and suspected fatty liver in children. We measured body mass index (BMI), z-score BMI, caliper ...skinfold thickness, waist and hip circumference in 94 participants (mean age 9.7 +/-2.2 years). Fasting blood glucose, insulin, HOMA score, lipid profile and transaminases (ALT, AST) were measured. Fatty liver and skinfold thickness were evaluated by means of ultrasound. The z-score BMI was 2.01 +/-0.39 (mean +/- SD), and the duration of obesity was 4.3+/-3.03 years. A positive correlation was found between caliper and US skinfold thickness for tricipital (r= 0.33; p= 0.003) and sovrailiac skinfold (r= 0.34; p=0.003). Fatty liver was diagnosed in 64% of children and it was positively related to anthropometric measurements. The three sub-groups--group 0 (normal US liver and normal transaminases); group 1 (US fatty liver and normal transaminases); group 2 (US fatty liver and elevated transaminases)--showed a difference concerning z-score BMI, insulin and HOMA parameters (Tukey test: z score BMI group 1 vs group 0 and 2 vs group 0; serum insulin: group 2 vs group 1 and group 2 vs group 0; HOMA IR: group 2 vs group 1 and group 2 vs group 0). Moderately obese children with steatosis exhibited a clear increase of insulin and insulin resistance which represents indices of a future metabolic syndrome. In addition, it is important to perform a liver ultrasound since transaminases seems to be not adequate for the diagnosis of fatty liver.
Sodium-dependent transporters regulate extracellular glutamate in the CNS. Recent studies suggest that the activity of several different neurotransmitter transporters can be rapidly regulated by a ...variety of mechanisms. In the present study, we report that pre-incubation of primary ‘astrocyte-poor’ neuronal cultures with glutamate (100 μM) for 30 min nearly doubled the
V
max for Na
+-dependent accumulation of
l-
3H-glutamate, but had no effect on Na
+-dependent
3H-glycine transport. Pre-incubation with glutamate also increased the net uptake of non-radioactive glutamate, providing evidence that the increase in accumulation of
l-
3H-glutamate was not related to an increase in intracellular glutamate and a subsequent increase in exchange of intracellular non-radioactive glutamate for extracellular radioactive glutamate. The glutamate receptor agonists, α-amino-3-hydroxy-5-methylisoxazole-4-propionate, quisqualate, and (1
S, 3
R)-1-aminocyclopentane-1,3-dicarboxylic acid did not mimic the effect of pre-incubation with glutamate and the glutamate-induced increase was not blocked by receptor antagonists. However, compounds known to interact with the transporters, including
l-aspartate,
d-aspartate,
l-(-)-threo-3-hydroxyaspartate (
l-THA) and
l-
trans-pyrrolidine-2,4-dicarboxylate (
l-
trans-PDC), caused variable increases in transport activity and attenuated the increase induced by glutamate, suggesting that the increase is related to the interaction of glutamate with the transporters. Several studies were attempted to define the mechanism of this regulation. We found no evidence for increases in transporter synthesis or cell surface expression. Inhibitors of signaling molecules known to regulate other neurotransmitter transporters had no effect on this stimulation. Using a variety of cultures, evidence is provided to suggest that this substrate-induced up-regulation of glutamate transport is specific for the GLT-1 and GLAST subtypes and does not influence transport mediated by EAAC1. These studies suggest that the interaction of glutamate with some of the subtypes of glutamate transporters causes an increase in transport activity. Conceivably, this phenomenon provides an endogenous mechanism to increase the clearance of glutamate during periods of prolonged elevations in extracellular glutamate.
Background
Few works have evaluated the effect of statins on left ventricular dysfunction in patients with chronic heart failure (CHF), by using tissue Doppler imaging (TDI). We therefore aimed to ...investigate whether atorvastatin treatment may influence prognosis and myocardial performance evaluated by TDI in subjects with CHF.
Methods
Five hundred thirty-two consecutive CHF outpatients enrolled in a local registry, the Daunia Heart Failure Registry, were prospectively analysed. 195 patients with CHF and left ventricular ejection fraction (LVEF) ≤40 %, either in treatment with atorvastatin (N: 114) or without statins (N: 81), underwent TDI examination. Adverse events were evaluated during follow-up.
Results
The atorvastatin group showed a lower incidence of adverse events (cardiac death: 0 % vs 7 %,
p
< 0.01), and better TDI performance (E/E’ 15 ± 5.7 vs 18 ± 8.3,
p
< 001) than controls. Ischaemic CHF patients in treatment with atorvastatin also showed a lower incidence of adverse events (death: 10 % vs 26 %,
p
< 0.05; sustained ventricular arrhythmias: 5 % vs 19 %,
p
< 0.05, cardiac death: 0 vs 8 %,
p
< 0.05) and better TDI performance (E/E’ ratio: 15.00 ± 5.68 vs 19.72 ± 9.14,
p
< 0.01; St: 353.70 ± 48.96 vs 303.33 ± 68.52 msec,
p
< 0.01) than controls. The association between atorvastatin and lower rates of cardiac death remained statistically significant even after correction in a multivariable analysis (RR 0.83, 95 % CI 0.71–0.96, p < 0.05 in CHF with LVEF ≤40 %; RR 0.77, 95 % CI 0.62–0.95,
p
< 0.05 in ischaemic CHF with LVEF ≤40 %).
Conclusions
Treatment with atorvastatin in outpatients with systolic CHF is associated with fewer cardiac deaths, and a better left ventricular performance, as assessed by TDI.
Aims
Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise ...test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction.
Methods and results
We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2‐ and 4‐year follow‐up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2‐year follow‐up, the prognostic accuracy of MECKI score was significantly superior area under the curve (AUC) 0.781 to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively).
Conclusion
In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2‐ and 4‐year follow‐up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.
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