Massive mitral regurgitation secondary to acute ischemic papillary muscle rupture: The role of echocardiography

Papillary muscle rupture is an infrequent but often fatal mechanical complication of acute myocardial infarction (AMI). We report the case of an AMI complicated by the development of an abrupt cardiogenic shock due to the rupture of the head of the postero-medial papillary muscle with echocardiographic demonstration of severe mitral regurgitation due to flail posterior mitral valve leaflet. After initial stabilization with medical therapy and diagnostic coronary angiography, the patient was referred for urgent cardiac surgery and successfully underwent mitral valve replacement with implantation of a bioprosthesis. This case confirms the importance of transthoracic echocardiography in diagnosing mechanical acute complications during an AMI and in the decision making of patients with sudden onset of hemodynamic compromise. Transthoracic echogardiography should be immediately carried out in all patients in whom a mechanical complication during an AMI is suspected. (Cardiol J 2010; 17, 4: 397-400

Nutritionally enriched tomatoes (Solanum lycopersicum L.) grown with wood distillate: chemical and biological characterization for quality assessment

: Bio-based products are nowadays useful tools able to affect the productivity and quality of conventionally cultivated crops. Several bio-based products are currently on the market; one of the newest and most promising is the wood distillate (WD) derived from the pyrolysis process of waste biomass after timber. Its foliar application has been widely investigated and shown to promote the antioxidant profile of cultivated crops. WD was used here as additive for the cultivation of tomato (Solanum lycopersicum L.) plants. The application improved quality (chemical) parameters, minerals, polyphenols, and lycopene contents of tomato fruits. The extracts of WD-treated and untreated tomatoes have been chemically and biologically characterized. The 1 H-NMR and ESI-mass spectrometry analyses of the extracts revealed the presence of different fatty acids, amino acids and sugars. In particular, the WD-treated tomatoes showed the presence of pyroglutamic acid and phloridzin derivatives, but also dihydrokaempferol, naringenin glucoside, cinnamic acid, and kaempferol-3-O-glucoside. When tested in cells, the extracts showed a promising anti-inflammatory profile in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the extracts displayed a slight vasorelaxant activity on rat aorta rings (either endothelium-denuded or endothelium-intact) pre-contracted with phenylephrine or potassium chloride. PRACTICAL APPLICATION: Wood distillate has been used for tomato plant growth. Tomatoes showed improved nutritional parameters, and their extracts displayed antioxidant and anti-inflammatory activities

Discovery of pyridoquinoxaline-based new P-gp inhibitors as coadjutant against Multi Drug Resistance in cancer

Multi-drug resistance (MDR) is a serious challenge in contemporary clinical practice and is mostly responsible for the failure of cancer medication therapies. Several experimental evidence links MDR to the overexpression of the drug efflux transporter P-gp, therefore, the discovery of novel P-glycoprotein inhibitors is required to treat or prevent MDR and to improve the absorption of chemotherapy drugs via the gastrointestinal system. In this work, we explored a series of novel pyridoquinoxaline-based derivatives designed from parental compounds, previously proved active in enhancing anticancer drugs in MDR nasopharyngeal carcinoma (KB). Among them, derivative 10d showed the most potent and selective inhibition of fluorescent dye efflux, if compared to reference compounds (MK-571, Novobiocin, Verapamil), and the highest MDR reversal activity when co-administered with the chemotherapeutic agents Vincristine and Etoposide, at non-cytotoxic concentrations. Molecular modelling predicted the two compound 10d binding mode in a ratio of 2:1 with the target protein. No cytotoxicity was observed in healthy microglia cells and off-target investigations showed the absence of CaV1.2 channel blockade. In summary, our findings indicated that 10d could potentially be a novel therapeutic coadjutant by inhibiting Pgp transport function in vitro, thereby reversing cancer multidrug resistance

Extra virgin olive oil extracts of indigenous Southern Tuscany cultivar act as anti-inflammatory and vasorelaxant nutraceuticals

Extra virgin olive oil (EVOO) is the typical source of fats in the Mediterranean diet. While fatty acids are essential for the EVOO nutraceutical properties, multiple biological activities are also due to the presence of polyphenols. In this work, autochthonous Tuscany EVOOs were chemically characterized and selected EVOO samples were extracted to obtain hydroalcoholic phytocomplexes, which were assayed to establish their anti-inflammatory and vasorelaxant properties. The polar extracts were characterized via 1H-NMR and UHPLC-HRMS to investigate the chemical composition and assayed in CaCo-2 cells exposed to glucose oxidase or rat aorta rings contracted by phenylephrine. Apigenin and luteolin were found as representative flavones; other components were pinoresinol, ligstroside, and oleuropein. The extracts showed anti-inflammatory and antioxidant properties via modulation of NF-κB and Nrf2 pathways, respectively, and good vasorelaxant activity, both in the presence and absence of an intact endothelium. In conclusion, this study evaluated the nutraceutical properties of autochthonous Tuscany EVOO cv., which showed promising anti-inflammatory and vasorelaxant effects

Traceability and authentication in agri-food production: a multivariate approach to the characterization of the Italian food excellence elephant garlic (Allium ampeloprasum L.), a vasoactive nutraceutical

A research platform for food authentication was set up by combining stable isotope ratio analysis, metabolomics by gas and liquid mass-spectrometry and NMR investigations, chemometric analyses for food excellences. This multi-analytical approach was tested on samples of elephant garlic (Allium ampeloprasum L.), a species belonging to the same genus of common garlic (Allium ampeloprasum L.), mainly produced in southern Tuscany-(Allium ampeloprasum). The isotopic composition allowed the product to be geographically characterized. Flavonoids, like (+)-catechin, cinnamic acids, quercetin glycosides were identified. The samples showed also a significant amount of dipeptides, sulphur-containing metabolites and glutathione, the latter of which could be considered a molecular marker of the analyzed elephant garlic. For nutraceutical profiling to reach quality labels, extracts were investigated in specific biological assays, displaying interesting vasorelaxant properties in rat aorta by mediating nitric oxide release from the endothelium and exhibited positive inotropic and negative chronotropic effects in rat perfused hear

Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology

[Can we learn to die?].

The topic of death and the dying is a crucial aspect of patient care, especially for individuals with terminal illnesses. However, discussions about death and dying are often avoided during patient interactions. In this article, our aim is to explore the reasons behind our fear of death and dying and to assess the importance of addressing these issues in shaping and cultivating relationships with our patients and in our personal lives. We argue that being open to impermanence is a valuable tool in our work with patients and their families and should be integrated into conversations with them. Furthermore, discussions about death and dying should play a central role in medical and nursing education as well as professional development

Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism

Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism