NMR characterization of animals’ follicular fluids

Follicular Fluid (FF) provides a special environment to the oocyte during its maturation in vivo. The FF is derived from the sanguineous plasma and secretions, synthesised in the follicle wall that contain a large variety of metabolites (1). These metabolites are probably involved in the physiology of the oocytes (1). The chemical composition of follicular fluids is important because it is an indicator of the secretory activities and metabolism of follicular cells and thus could be related to the follicular quality. It could also provide a useful indication of the oocyte growth and maturation (2). High Resolution Nuclear Magnetic Resonance (NMR) spectroscopy provides a unique tool for studying metabolites. Initially, NMR spectroscopy was used mainly in biomedicine but it is found now in many physiological applications (3). As the NMR spectroscopy provides opportunities for obtaining qualitative and quantitative data from body fluids, it was hypothesized that this technique could provide information on mammals’ follicular fluid and on intrafollicular changes that occur during follicular growth and ovulation. As some of these changes are probably of crucial importance for oocyte developmental competence, a better knowledge of the mammals’ follicular fluid composition by 1H NMR analysis should help to resolve some of the problems encountered during in vitro procedures in the mammals. The characterization of the chemical composition of mammals follicular fluids, namely sheep, cattle, mare and pork, and the study of the changes observed during follicular growth and maturation using NMR spectroscopy will be presented. FF samples were collected from antral follicle of different dimensions. One-dimensional (1D) 1H experiments (CPMG, DOSY) were obtained for all the FF samples. In addition, several two dimensional (2D) (homo and heteronuclear) experiments (DQF-COSY, TOCSY, JRES, 1H-13C HSQC) were performed to aid in the assignment of the signals and in the identification of the metabolites in FF. A direct evaluation of the lipids, carbohydrates and metabolites were obtained from the combination of the 1D and 2D NMR experiments

Landscape planning and ecological networks: part A: a rural system in Nuoro, Sardinia

Urban-rural landscape planning research is nowadays focusing on strategies and tools that support practitioners in designing integrated spaces starting from the analysis of local areas, where human and natural pressures interfere. A prominent framework is provided by the ecological networks, whose design regards the combination of a set of green areas or patches (the nodes) interconnected through environmental corridors (the edges). Ecological networks are useful for biodiversity protection and enhancement, as they are able to counteract fragmentation, and to create or strengthen relations and exchanges among otherwise isolated elements. Biodiversity evolution, indeed, depends on the quantity and quality of spatial cohesion of natural areas. In this paper, we aim at designing an ecological network for the periurban area on the town of Nuoro in central Sardinia. The narrative unfolds in two parts. Part A is presented in this paper and includes its methodological premises, i.e. biodiversity conservation and ecological network analysis and design, and the introductory elements of a spatial analysis on a pilot ecological network of one hundred patches. We locate patches by focusing on the ecosystems supported by the target vegetal species holm oak (Quercus ilex) and cultivated or wild olive (Olea europaea var. sativa, O. europaea var. sylverstis). These are very common plants species in the municipality and some animal species are active as seed dispersal. The reminder, i.e. Part B, of the essay is presented in an homonymous paper that focuses on the illustration of the network analysis conceived as a monitoring system and, in future perspective, as a planning support system

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Interaction of Cu(II) and Ni(II) with Park9 Protein fragments via NMR Studies

A fragment of Ypk9 protein, P1D2E3K4H5E6L7 (PK9-H), was studied for its coordination abilities towards Ni(II) and Cu(II) ions through mono- and bidimensional NMR techniques. Park9 belongs to the P5-type ATPase family; its mutation is able to induce a juvenile form of Parkinsonism in humans, and seems to be connected to manganese poisoning in both yeasts and humans. For this reason, some significant sequences of Park9 and the yeast homologue Ypk9 have been already investigated forMn(II) binding. The proteins belong to an ATPase (P5 type) family involved in the transportation of metal ions, including manganese and nickel, from the cytosol to the lysosomal lumen. Here, we tested PK9-H with Cu(II) and Ni(II) ions; the former because it is an essential element ubiquitous in the human body, so its trafficking should be strictly regulated and one cannot exclude that Ypk9 may play a role in it, and the latter because, besides being a toxic element for many organisms and being involved in different pathologies and inflammation states, it seems that the protein confers protection against it. Furthermore, nickel ions in the proper coordination geometry could be a good diamagnetic probe for metal binding. NMR experiments showed that both cations can bind PK9-H in an effective way, leading to complexes whose coordination mode depends on the pH of the solution. NMR data have been used to build a model for the structure of the major Cu(II) and Ni(II) complexes. Structural changes in the conformation of the peptide with organized side chain orientation promoted by nickel coordination were detected

Hydroxylated biphenyl derivatives are positive modulators of human GABA_A receptors

A series of 7 hydroxylated biphenyl derivatives (1–7) were prepared to evaluate their ability to modulate the function of several ligand gated ion channel (LGIC) recombinant receptors expressed in Xenopus laevis oocytes. Compounds 1, 3, 4, 6 and 7 are natural occurring compounds whereas the synthesis of compounds 2 and 5 was previously reported ( Delogu et al., 2004 and Fabbri et al., 2007). None of the compounds tested were able to modify, the activity of the strychnine-sensitive glycine receptor, or the activity of nicotinic receptor. The function of the 5HT3A receptor was partially inhibited by all compounds tested, however this inhibition occurred at relatively high concentrations (100 μM). All compounds, with the exception of compound 6, potentiate the action of gamma-aminobutyric acid (GABA)-evoked Cl− currents in Xenopus laevis oocytes expressing recombinant human α1β2γ2L GABAA receptors. Compounds 1, 2, 5 and 7 enhance the function of the GABAA receptor at concentrations higher than 3–10 μM. Compound 4 was the most efficacious. However, compound 3 was the most potent (EC50 0.8 μM). The potency of compound 3 in modulating the function of the GABAA receptor was comparable to that of diazepam, propofol or allopregnanolone. The enhancement of the GABA evoked Cl− currents by compound 3 was not affected by flumazenil. Compound 3 did not induce loss of the righting reflex in rats suggesting that it is not an anesthetic agent, however, its ability in protecting the animals from seizures induced by picrotoxin confirm that its action occurs through the GABAA receptor

Landscape Planning and Ecological Networks. Part B. A Rural System in Nuoro, Sardinia

This paper represents the continuation, i.e. Part B, of an homonymous paper aiming at designing an ecological network for the periurban area on the town of Nuoro in central Sardinia. While in Part A we illustrate the methodological premises and introduce a spatial network analysis-based study of a pilot ecological network, in this paper we apply a complex network analysis approach to the construction and characterization of the dynamics of the ecological network of Nuoro.  We are interested in monitoring the performance of the ecological network evolving from a real to a hypothetical scenario, where the two target vegetal species (holm oak and cultivated or wild olive) are present in each patch. We focus on global network properties and on three different centrality measures: degree, clustering coefficient, and betweenness centrality. We also take into account the influence of the intensity of the connection (i.e. the weight) by introducing the corresponding weighted centrality measures. Through thematic mapping we illustrate the pattern of each centrality indicator throughout the entire pilot set of patches. In this way, we demonstrate how spatial network analysis is useful to monitor the performance of the network and to support decision-making, management, and planning

Landscape Planning and Ecological Networks. Part B. A Rural System in Nuoro, Sardinia

This paper represents the continuation, i.e. Part B, of an homonymous paper aiming at designing an ecological network for the periurban area on the town of Nuoro in central Sardinia. While in Part A we illustrate the methodological premises and introduce a spatial network analysis-based study of a pilot ecological network, in this paper we apply a complex network analysis approach to the construction and characterization of the dynamics of the ecological network of Nuoro.  We are interested in monitoring the performance of the ecological network evolving from a real to a hypothetical scenario, where the two target vegetal species (holm oak and cultivated or wild olive) are present in each patch. We focus on global network properties and on three different centrality measures: degree, clustering coefficient, and betweenness centrality. We also take into account the influence of the intensity of the connection (i.e. the weight) by introducing the corresponding weighted centrality measures. Through thematic mapping we illustrate the pattern of each centrality indicator throughout the entire pilot set of patches. In this way, we demonstrate how spatial network analysis is useful to monitor the performance of the network and to support decision-making, management, and planning

Documento di consenso ANMCO/SIC/SICI-GISE/SICCH: Approccio clinico al pretrattamento farmacologico in pazienti candidati a procedure di rivascolarizzazione miocardica

The wide availability of drugs effective in reducing cardiovascular events and the use of myocardial revascularization have greatly improved the prognosis of patients with coronary artery disease. However, the combination of antithrombotic drugs to be administered before the exact knowledge of the coronary anatomy and before the consequent therapeutic strategy can, on one hand, allow to anticipate an optimal treatment but, on the other hand, may expose the patient to a bleeding risk not always necessary. In patients with ST-elevation acute coronary syndrome with an indication to primary angioplasty, the administration of unfractionated heparin and aspirin is considered the pre-procedural standard treatment. The upstream administration of an oral P2Y12 inhibitor, even if not supported by randomized controlled trials, appears reasonable in view of the very high likelihood of treatment with angioplasty. In patients with non-ST elevation acute coronary syndrome, in which it is not always chosen an invasive strategy, the occurrence of bleeding can significantly weigh on prognosis, even more than the theoretical benefit of pretreatment. Fondaparinux is the anticoagulant with the most favorable efficacy/safety profile. Antiplatelet pretreatment must be selective, guided by the ischemic risk conditions, the risk of bleeding and the time schedule for coronary angiography.In patients with stable coronary artery disease, generally treated with aspirin, pretreatment with clopidogrel is advisable in case of already scheduled angioplasty, and it appears reasonable in case of high likelihood, at least in patients at low bleeding risk. In patients candidate to surgical revascularization, aspirin is typically maintained and the oral P2Y12-inhibitor discontinued, with i.v. antiplatelet drug bridging in selected cases.Anti-ischemic drugs are useful in controlling symptoms, but they have no specific indications with regard to revascularization procedures. Statins showed protective effects on periprocedural damage and late clinical events, when administered early. Although randomized data are lacking, it seems reasonable their pre-procedural administration, due to potential advantages without significant adverse effects