Mono- and dicationic DABCO/Quinuclidine composed nanomaterials for the loading of steroidal drug: 32 factorial design and physicochemical characterization

Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration.This work was funded by the Portuguese Science and Technology Foundation (FCT) from the Ministry of Science and Technology (MCTES), European Social Fund (FSE) of EU, for the scholar ship SFRH/BD/130555/2017 granted to A. R. Fernandes, and for the projects UIDB/04469/2020 (CEB strategic fund) and UIDB/04033/2020 (CITAB), co-funded by European Funds (PRODER/COMPETE) and FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Sugar-lowering drugs for type 2 diabetes mellitus and metabolic syndromestrategies for in vivo administration: Part-II

Diabetes is a complex disease characterized by hyperglycemia, together with polyuria, polydipsia, and polyphagia. While Type 1 diabetes mellitus (T1DM) results from genetic, environmental, or immune dysfunction factors leading to pancreatic ß-cell destruction depriving the organism from endogenous insulin, Type 2 diabetes mellitus (T2DM) is characterized by peripheral insulin resistance. Depending on the type of diabetes mellitus and drug mechanism to study, the animal model should be carefully selected among the wide variety of the currently available ones. This review discusses the most common animal models currently employed to study T1DM and T2DM. Moreover, an overview on the administration routes that could be used is also discussed.The authors acknowledge the financial support received from Portuguese Science and TechnologyFoundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project referenceM-ERA-NET/0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020. The authors also acknowledge the support of the Institute of Nanoscience and Nanotechnology under the project ART (2018).info:eu-repo/semantics/publishedVersio

Sugar-lowering drugs for type 2 diabetes mellitus and metabolic syndrome - review of classical and new compounds: Part-I

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia together with disturbances in the metabolism of carbohydrates, proteins and fat, which in general results from an insulin availability and need imbalance. In a great number of patients, marketed anti-glycemic agents have shown poor effectiveness in maintaining a long-term glycemic control, thus being associated with severe adverse effects and leading to an emerging interest in natural compounds (e.g., essential oils and other secondary plant metabolites, namely, flavonoid-rich compounds) as a novel approach for prevention, management and/or treatment of either non-insulin-dependent diabetes mellitus (T2DM, type 2 DM) and/or Metabolic Syndrome (MS). In this review, some of these promising glucose-lowering agents will be comprehensively discussed.This work was financially supported by the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference M-ERANET/0004/2015-PAIRED and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020, and also by the Institute of Nanoscience and Nanotechnology under the project ART(2018).info:eu-repo/semantics/publishedVersio

DABCO-customized nanoemulsions: characterization, cell viability and genotoxicity in retinal pigmented epithelium and microglia cells

Quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and of quinuclidine surfactants were used to develop oil-in-water nanoemulsions with the purpose of selecting the best long-term stable nanoemulsion for the ocular administration of triamcinolone acetonide (TA). The combination of the best physicochemical properties (i.e., mean droplet size, polydispersity index, zeta potential, osmolality, viscoelastic properties, surface tension) was considered, together with the cell viability assays in ARPE-19 and HMC3 cell lines. Surfactants with cationic properties have been used to tailor the nanoemulsions surface for site-specific delivery of drugs to the ocular structure for the delivery of TA. They are tailored for the eye because they have cationic properties that interact with the anionic surface of the eye.Portuguese Science and Technology Foundation (FCT) from the Ministry of Science and Technology (MCTES), European Social Fund (FSE) of the EU, for the scholarship SFRH/BD/130555/2017 granted to A. R. Fernandes, and for the projects UIDB/04469/2020 (CEB strategic fund) and UIDB/04033/2020 (CITAB), co-funded by European Funds (PRODER/COMPETE) and FEDER, under the Partnership Agreement PT2020info:eu-repo/semantics/publishedVersio

Metal-based nanoparticles as antimicrobial agents: an overview

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.M.L.G., M.E. (Miren Ettcheto), A.C., and E.S.L. belong to 2017SGR-1477. E.S.-L., A.C., M.E. (Marta Espina), and M.L.G. acknowledge the support of Institute of Nanoscience and Nanotechnology (ART2018 project). E.B.S. wants to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) for the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, co-funded by FEDER, under the partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Diabetic retinopathy and ocular melanoma: how far we are?

Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.The authors acknowledge the financial support received from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERANET/0004/2015-PAIRED, UIDB/04469/2020 (strategic fund) and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020. The authors also acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Exports and Productivity: Comparable Evidence for 14 Countries

We use comparable micro level panel data for 14 countries and a set of identically specified empirical models to investigate the relationship between exports and productivity. Our overall results are in line with the big picture that is by now familiar from the literature: Exporters are more productive than non-exporters when observed and unobserved heterogeneity are controlled for, and these exporter productivity premia tend to increase with the share of exports in total sales; there is strong evidence in favour of self-selection of more productive firms into export markets, but nearly no evidence in favour of the learning-by-exporting hypothesis. We document that the exporter premia differ considerably across countries in identically specified empirical models. In a meta-analysis of our results we find that countries that are more open and have more effective government report higher productivity premia. However, the level of development per se does not appear to be an explanation for the observed cross-country differences.exports; productivity; micro data; international comparison

The importance of vertical transmission of Neospora sp. in naturally infected horses

AbstractNeospora spp. is a intracellular protozoan phylogenetically closely related to Toxoplasma gondii and Sarcocystis neurona, and it can infect horses leading to the development of reproductive or neurological diseases. We determined the presence of antibodies to Neospora sp. in mares at their parturition time and determine the frequency of vertical transmission in healthy foals to verify the importance of transplacental transmission. The samples were analyzed by indirect immunofluorescence antibody test, showing that seroprevalence in mares is higher than in foals and seropositive mares are likely to transmit the neosporosis to their offspring. This shows that endogenous challenge occurs in horses, and it suggests that this protozoan can be disseminated by means of transplacental transmission in horse species

Stress echo 2020 : the international stress echo study in ischemic and non-ischemic heart disease

Background: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. Methods: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). Results: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. Conclusions: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls

Berberine, a popular dietary supplement for human and animal health: Quantitative research literature analysis a review

Berberine is an alkaloid with a wide range of reported beneficial health effects. The current work provides an extensive literature analysis on berberine. Bibliometric data were identified by means of the search string TOPIC=(berberin* OR umbellatine*), which yielded 5,547 publications indexed in the Web of Science Core Collection electronic database. The VOSviewer software generated bubble maps to visualize semantic terms with citation results. The ratio of original articles to reviews was 13.6:1. The literature has been growing more quickly since the 2010s. Major contributing countries were China, the United States, India, Japan, and South Korea. Most of the publications appeared in journals specialized in pharmacology pharmacy, biochemistry molecular biology, chemistry, and plant science. Some of the frequently mentioned chemicals/chemical classes were alkaloid, palmatine, jatrorrhizine, coptisine, isoquinoline, and sanguinarine. The prevalent medical conditions under investigation included Alzheimers disease, cancer, diabetes, and obesity.Acknowledge the support by the Polish KNOW (LeadingNational Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015 and the European Union under the European Regional Development Fund (Homing/2017-4/41). Antoni Sureda has been supported by the Institute of Health Carlos III (Project CIBEROBN CB12/03/30038). Joanna Feder-Kubis was financed by the Polish Ministry of Science and Higher Education for the Faculty of Chemistry of Wrocław University of Science and Technology.info:eu-repo/semantics/publishedVersio