Abstract
Background. Intense training can lead to a pathophysiological change in serum concentration of a variety of biomarkers. Traditional biomarkers of cardiac injury are very useful in monitoring ...CVD patients, but in healthy subjects or athletes they cannot be informative enough about the cardiovascular risk, because in these cases their serum levels do not increase over the pathological limit. Therefore novel cardiovascular biomarkers are required in order to allow a better monitoring of sport performance, prediction of overtraining and diagnosis of sport-related cardiac injuries. Growth differentiation factor-15 (GDF-15) is emerging as a powerful cardiovascular injury risk indicator. In this study we investigate the effect of intense physical training of on the circulating levels of GDF-15 in rugby professional players. Methods. Serum GDF-15, Erythropoietin, IL-6, the cardiovascular parameter ST-2, NT-proBNP and routine hematological parameters were measured in a group of 30 rugby players before and after a session of intense training. Results. While ST-2, IL-6 and hsCRP displayed no significant changes after intense training, NT-proBNP and GDF-15 showed a significant increase, even without reaching the pathological level. Discussion. The measure of GDF-15 in professional rugby players could be a useful tool to monitoring their cardiovascular status during training and competition session in order to prevent the onset of collateral cardiovascular adverse event due to the intense training and, in the case of cardiac injury, it could possibly allow a very early diagnosis at the beginning of the pathogenic process.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background/Aims: Diuretic treatment of ascites could result in intravascular volume depletion, electrolyte imbalance and renal impairment. We investigated whether intravascular volume expansion with ...albumin exert beneficial effects in cirrhosis with ascites.
Methods: In protocol 1, 126 cirrhotic inpatients in whom ascites was not relieved following bed rest and a low-sodium diet, were randomly assigned to receive diuretics (group A) or diuretics plus allbumin, 12.5 g/day (group B). In protocol 2, group A patients continued to receive diuretics and group B diuretics plus albumin (25 g/week) as outpatients and were followed up for 3 years. End points were: disappearance of ascites, duration of hospital stay (protocol 1), recurrence of ascites, hospital readmission and survival (protocol 2).
Results: The cumulative rate of response to diuretic treatment of ascites was higher (
p<0.05) and hospital stay was shorter (20±1 versus 24±2 days,
p<0.05) in group B than in group A patients. After discharge, group B patients had a lower cumulative probability of developing ascites (19%, 56%, 69% versus 30%, 79% and 82% at 12,24 and 36 months,
p<0.02) and a lower probability of readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively,
p<0.02). Survival was similar in the two groups.
Conclusions: Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2.
Neuroimaging research of fluid intelligence (Gf) has mainly focused on the neural basis of abilities explaining performance on cognitive tasks. However, the neuro-functional basis of clearly defined ...theoretical cognitive components underlying Gf remains unclear. Induction, visualization, and spatial relationships have the highest relevance for Gf (Carroll, 1993). Here we report a functional magnetic resonance imaging (fMRI) study exploring the neural correlates of these abilities characterized by their unidimensionality and matched for task-difficulty, as evidenced by a psychometric calibration study. Twenty-two healthy young adult females, recruited from a large sample of 300 participants, with either below- or above-average Gf abilities underwent fMRI scanning during Gf task performance. The results reveal that these tasks activate a shared frontoparietal network. Specific activations were also observed, in particular for induction and visualization. The key findings suggest that Gf comprises distinguishable cognitive abilities, but the Gf construct is associated with a common network.
Olfactory neurons and gonadotropin-releasing hormone (GnRH) neurons share a common origin during organogenesis. Kallmann's syndrome, clinically characterized by anosmia and hypogonadotropic ...hypogonadism, is due to an abnormality in the migration of olfactory and GnRH neurons. We recently characterized the human FNC-B4 cell line, which retains properties present in vivo in both olfactory and GnRH neurons. In this study, we found that FNC-B4 neurons expressed GnRH receptor and responded to GnRH with time- and dose-dependent increases in GnRH gene expression and protein release (up to 5-fold). In addition, GnRH and its analogs stimulated cAMP production and calcium mobilization, although at different biological thresholds (nanomolar for cAMP and micromolar concentrations for calcium). We also observed that GnRH triggered axon growth, actin cytoskeleton remodeling, and a dose-dependent increase in migration (up to 3-4-fold), whereas it down-regulated nestin expression. All these effects were blocked by a specific GnRH receptor antagonist, cetrorelix. We suggest that GnRH, secreted by olfactory neuroblasts, acts in an autocrine pattern to promote differentiation and migration of those cells that diverge from the olfactory sensory lineage and are committed to becoming GnRH neurons.
4-Hydroxynonenal (HNE) is a putative pro-fibrogenic product of oxidative stress able to elicit apoptosis and cytotoxicity in several cell types. This study has been performed to evaluate its 'in ...vivo' levels in injured liver and whether HNE may induce apoptosis and/or affect selected phenotypic responses in activated human hepatic stellate cells (HSC/MF).
During the development of acute liver injury induced by CCl(4), liver tissue HNE levels were in the range 0.5-10 microM, as shown by high performance liquid chromatography analysis. Cultured human HSC/MF, developed cytotoxicity only if exposed to very high HNE concentrations (25-50 microM) without any sign of induction of classic, caspase-dependent apoptosis, as assessed by evaluating morphology and biochemical parameters of cell death. HNE, at non-cytotoxic doses, up-regulated procollagen type I and tissue inhibitor of metalloproteinases-1 gene expression and/or protein synthesis without significantly affecting chemotaxis (wound healing and haptotaxis assay), matrix metalloproteinases 1 and 2 mRNA expression and activity as well as basal DNA synthesis.
HNE, at concentrations compatible with those detected in vivo, does not elicit HSC/MF classic apoptosis but, rather, may act as a potent pro-fibrogenic stimulus for the expression of genes involved in excess extracellular matrix deposition and proposed as survival signals for HSC/MF.
The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such ...functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)–dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC–dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC–dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain–behavior relationships. On the basis of our results, it is proposed that the aIC–dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions.
•The aIC–dACC/mFC network is dynamically organized according to specific task states.•Long-range functional coupling yields information about brain–behavior relationships.•Anterior insula interacts with visual cortex during visuospatial reasoning.•Medial frontal–anterior frontal cortex coupling is enhanced during induction.•Network interactions support task-common and task-specific information integration.
Background & Aims: Nitrovasodilators have been proposed for the treatment of portal hypertension alone or in combination with β-blockers. In addition to their vasodilatory properties, nitric oxide ...(NO) donors may exert direct antifibrogenic properties. We evaluated the effect of nitroglycerin (NTG) and S-nitroso-N-acetyl penicillamine (SNAP) on the mitogenic and chemotactic properties of platelet-derived growth factor (PDGF)-BB and the modulation of the relative intracellular signaling pathways in fully activated human hepatic stellate cells (HSCs), a cell type that plays an active role in liver fibrogenesis and portal hypertension. Methods & Results: Both NTG and SNAP induced a dose-dependent decrease in PDGF-induced DNA synthesis and cell migration, which was associated with a decrease in PDGF-induced intracellular Ca2+ increase and extracellular signal-regulated kinase (ERK) activity. These effects were not related to activation of the classic soluble guanylate cyclase (sGC)/guanosine 3',5'-cyclic monophosphate pathway; accordingly, Western blot analysis of HSC lysates revealed the absence of the α1β1 ubiquitous subunits of sGC, whereas they were detectable in quiescent HSCs, freshly isolated from normal human liver. Conversely, both NTG and SNAP induced a more than 10–20-fold increase in prostaglandin E2 in cell supernatants within 1 minute, associated with an increase in intracellular adenosine 3',5'-cyclic monophosphate levels. Accordingly, the inhibitory effects of NO donors on PDGF action and signaling were eliminated after preincubation with ibuprofen. Conclusions: These results suggest that NO donors may exert a direct antifibrogenic action by inhibiting proliferation, motility, and contractility of HSCs in addition to a reduction of fibrillar extracellular matrix accumulation.
GASTROENTEROLOGY 2000;119:479-492
Background Cardiac autonomic dysfunction has been associated with cognitive impairment, but the underlying pathogenesis is complex and cerebral white matter lesions (WMLs) might be implicated. ...Methods Time and frequency heart rate variability (HRV) and visual rating of WMLs were carried out in 42 patients with mild cognitive impairment. Results After adjustment for relevant demographic and clinical characteristics, including left ventricular mass, reduced HRV indices of parasympathetic (root mean square of successive difference of RR intervals, RMSSD) and sympathetic modulation (low-frequency LF power) were associated with increased WML score (RMSSD: B −0.30, 95% CI −0.52 to −0.08, p = .01; LF: B −0.24, 95% CI −0.46 to −0.02, p = .05). In a multiple-adjusted model, RMSSD was the major independent predictor of WMLs (B −0.35, 95% CI −0.57 to −0.13, p = .002). Conclusion The evidence for an independent association of cardiac autonomic dysfunction with WMLs might suggest its role in the pathogenesis of WMLs.