Phytochemical investigations on Artemisia alba Turra growing in the North-East of Italy

Artemisia alba Turra (Asteraceae) is an Euro-Mediterranean plant used in Veneto (North-East of Italy) as traditional medicine for the treatment of various diseases. A. alba is a taxonomically problematic species, characterized by common polymorphism leading to a quite high variability in secondary metabolites content. Nonetheless, the phytochemical knowledge on its phytoconstituents, especially non-volatile components, is limited. In the present paper, the phytochemical composition of a tincture obtained from the aerial parts of A. alba growing in Veneto is presented. Extensive chromatographic separations led to the isolation of three new sesquiterpene derivatives, whose structures were elucidated by 1D and 2D NMR experiments and mass spectrometry. Furthermore, flavonoid composition and volatile constituents of the tincture of A. alba were preliminary studied by HPLC-MSn and GC-MS, respectivel

EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy

The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R = -0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N = 40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes' cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium

On the Mitra-Wan Forest Management Problem in Continuous Time

The paper provides a continuous time version of the well known discrete time Mitra-Wan model of optimal forest management, where a forest is harvested to maximize the utility of timber flow over an infinite time horizon. Besides varying with time, the state variable (describing available trees) and the other parameters of the problem vary continuously also with respect to the age of the trees. The evolution of the system is given in terms of a partial differential equation and later rephrased as an ordinary differential equation in an infinite dimensional space. The paper provides a classification of the behavior of optimal and maximal programs when the utility function is linear, convex, or strictly convex and the discount rate is positive or null. Formulas are provided for modified golden-rule configurations (uniform density functions with cutting at the ages that solve a Faustmann problem) and for Faustmann policies, and the optimality or maximality of such programs is discussed. In all different sets of data, it is shown that the optimal (or maximal) control is necessarily something more general than a function, i.e. a positive measure. In particular, in the case of strictly concave utility and null discount, when the Faustmann policy is not optimal, it is shown that optimal paths converges over time to the golden rule configuration, while in the case of strictly concave utility and positive discount the Faustmann policy is shown to be not optimal, contradicting the corresponding result in discrete time

Direct evidence for microdomain-specific localization and remodeling of functional L-type calcium channels in rat and human atrial myocytes

Background—Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). Methods and Results—Isolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy. Half of AMs possessed T-tubules and structured topography, proportional to cell width. A bigger proportion of myocytes in the left atrium had organized T-tubules and topography than in the right atrium. Super-resolution scanning patch clamp showed that LTCCs distribute equally in T-tubules and crest areas of the sarcolemma, whereas, in ventricular myocytes, LTCCs primarily cluster in T-tubules. Rat, but not human, T-tubule LTCCs had open probability similar to crest LTCCs, but exhibited ≈40% greater current. Optical mapping of Ca2+ transients revealed that rat AMs presented ≈3-fold as many spontaneous Ca2+ release events as ventricular myocytes. Occurrence of crest LTCCs and spontaneous Ca2+ transients were eliminated by either a caveolae-targeted LTCC antagonist or disrupting caveolae with methyl-β-cyclodextrin, with an associated ≈30% whole-cell ICa,L reduction. Heart failure (16 weeks post–myocardial infarction) in rats resulted in a T-tubule degradation (by ≈40%) and significant elevation of spontaneous Ca2+ release events. Although heart failure did not affect LTCC occurrence, it led to ≈25% decrease in T-tubule LTCC amplitude. Conclusions—We provide the first direct evidence for the existence of 2 distinct subpopulations of functional LTCCs in rat and human AMs, with their biophysical properties modulated in heart failure in a microdomain-specific manner

Isotopic effects in sub-barrier fusion of Si + Si systems

Background: Recent measurements of fusion cross sections for the 28Si+28Si system revealed a rather unsystematic behavior ; i.e., they drop faster near the barrier than at lower energies. This was tentatively attributed to the large oblate deformation of 28Si because coupled-channels (CC) calculations largely underestimate the 28Si+28Si cross sections at low energies, unless a weak imaginary potential is applied, probably simulating the deformation. 30Si has no permanent deformation and its low-energy excitations are of a vibrational nature. Previous measurements of this system reached only 4 mb, which is not sufficient to obtain information on effects that should show up at lower energies. Purpose: The aim of the present experiment was twofold: (i) to clarify the underlying fusion dynamics by measuring the symmetric case 30Si+30Si in an energy range from around the Coulomb barrier to deep sub-barrier energies, and (ii) to compare the results with the behavior of 28Si+28Si involving two deformed nuclei. Methods: 30Si beams from the XTU tandem accelerator of the Laboratori Nazionali di Legnaro of the Istituto Nazionale di Fisica Nucleare were used, bombarding thin metallic 30Si targets (50 μg/cm2) enriched to 99.64% in mass 30. An electrostatic beam deflector allowed the detection of fusion evaporation residues (ERs) at very forward angles, and angular distributions of ERs were measured. Results: The excitation function of 30Si+30Si was measured down to the level of a few microbarns. It has a regular shape, at variance with the unusual trend of 28Si+28Si. The extracted logarithmic derivative does not reach the LCS limit at low energies, so that no maximum of the S factor shows up. CC calculations were performed including the low-lying 2+ and 3− excitations. Conclusions: Using a Woods-Saxon potential the experimental cross sections at low energies are overpredicted, and this is a clear sign of hindrance, while the calculations performed with a M3Y + repulsion potential nicely fit the data at low energies, without the need of an imaginary potential. The comparison with the results for 28Si+28Si strengthens the explanation of the oblate shape of 28Si being the reason for the irregular behavior of that system

Validation of a New Classification Method of Postoperative Complications in Patients Undergoing Coronary Surgery

International audienceObjective The authors aimed to validate the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) classification of postoperative complications in patients undergoing coronary artery bypass grafting (CABG). Design Retrospective, observational study. Setting University hospital. Participants A total of 2,764 patients with severe coronary artery disease. Complete baseline, operative, and postoperative data were available for patients who underwent isolated CABG. Interventions Isolated CABG. Measurements and Main Results The E-CABG complication classification was used to stratify the severity and prognostic impact of adverse postoperative events. Primary outcome endpoints were 30-day, 90-day, and long-term all-cause mortality. The secondary outcome endpoints was the length of intensive care unit stay. Both the E-CABG complication grades and additive score were predictive of 30-day (area under the receiver operating characteristics curve 0.866, 95% confidence interval [CI] 0.829-0.903; and 0.876; 95% CI 0.844-0.908, respectively) and 90-day (area under the receiver operating characteristics curve 0.850, 95% CI 0.812-0.887; and 0.863, 95% CI 0.829-0.897, respectively) all-cause mortality. The complication grades were independent predictors of increased mortality at actuarial (log-rank: p&lt;0.0001) and adjusted analysis (p&lt;0.0001; grade 1: hazard ratio [HR] 1.757, 95% CI 1.111-2.778; grade 2: HR 2.704, 95% CI 1.664-4.394; grade 3: HR 5.081, 95% CI 3.148-8.201). When patients who died within 30 days were excluded from the analysis, this grading method still was associated with late mortality (p&lt;0.0001). The grading method (p&lt;0.0001) and the additive score (rho, 0.514; p&lt;0.0001) were predictive of the length of intensive care unit stay. Conclusions The E-CABG postoperative complication classification seems to be a promising tool for stratifying the severity and prognostic impact of postoperative complications in patients undergoing cardiac surger

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

A crescente necessidade de informação para a tomada de decisões dos gestores do setor do transporte urbano de passageiros obriga a desenvolver sistemas para o cálculo, análise e controle de custos que permitam conhecer de forma acurada os mecanismos de formação dos seus preços internos. Nesse contexto, a medida do rendimento adquire um interesse especial quando é comparada a parâmetros e padrões significativos, que permitam aplicar técnicas de benchmarking para melhorar a gestão econômica do serviço. Com esses fins, entende-se que a geração de medidas representativas de padrões coletivos de comportamento constitui-se em uma ferramenta útil para orientar a ação de gestores e administradores públicos. E, como conseqüência, nós apresentamos à Asociación de Empresas de Transporte Urbano Colectivo (ATUC), na Espanha, um projeto para a criação de um Observatório de Custos que possa constituir-se em um importante ponto de referência para as empresas de transporte urbano de passageiros. Palavras-chave: Custos. Financiamento. Transporte urbano de passageiros. * Trabalho apresentado no XIII Congresso Brasileiro de Custos, realizado em Belo Horizonte – MG, no período de 30 de outubro a 01 de novembro 2006.The possibility of providing more complete and detailed data about passenger transport enterprises management justifies the development of analysis and cost control systems that provide precise and rigorous knowledge about internal price formation mechanisms. In this framework, measurement of performance is especially relevant when compared with some other significant reference parameters that allow the use of benchmarking in order to improve the economic management of the service. To this end, we consider it especially useful for the ATUC (Asociación de Empresas de Transporte Urbano Colectivo, i.e., the Association of Collective Urban Transport Companies) to provide a service that establishes measures which represent actual behaviour patterns, that enhances the knowledge of the reality of the sector and that generates a spirit of self-improvement in their associates. We presented a project to ATUC proposing the establishment of a Costs Observatory that can become a significant reference point for passenger transport companies. Key words: Costs. Funding. Urban Passenger Transport.Las crecientes necesidades de información para la gestión y la toma de decisiones de los agentes que operan en el sector del transporte urbano de pasajeros, obliga a desarrollar sistemas para el cálculo, análisis y control de costes que permitan un conocimiento riguroso de los mecanismos de formación de sus precios internos. En dicho marco, la medida del rendimiento adquiere especial interés cuando entra en comparación con parámetros y estándares significativos, que permitan aplicar técnicas de benchmarking para mejorar la gestión económica del servicio. A tales efectos, entendemos que la generación de medidas representativas de patrones colectivos de comportamiento, constituye una herramienta de gran utilidad para orientar la acción de gestores y administradores públicos. Y, en consecuencia, en España, y en el seno de la Asociación de Empresas de Transporte Urbano Colectivo (ATUC), estamos desarrollando un proyecto para la creación de un Observatorio de Costes que pueda constituirse en significativo punto de referencia para las empresas de transporte urbano de viajeros. Palabras clave: Costes. Financiación.Transporte urbano de viajeros

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1β (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart

Exosomes: From potential culprits to new therapeutic promise in the setting of cardiac fibrosis

Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents