Avaliação e Caraterização da Ação Inibitória de Iminociclitóis na Atividade α-Glucosidase de Enterócitos de Mamífero

A diabetes, em particular a diabetes mellitus tipo 2, constitui um distúrbio metabólico que se carateriza por glicemias aumentadas resultantes de diminuição da libertação e/ou ação da insulina. Os inibidores das α-glucosidases surgem como agentes de elevado interesse terapêutico uma vez que podem contribuir para a diminuição da absorção intestinal de glicose e, consequentemente, para um desagravamento da hiperglicemia. Alguns compostos da família iminociclitol são inibidores das α- glucosidases [1] e têm vindo a ser sintetizados diversos compostos novos que podem ser promissores e cuja ação sobre a atividade α-glucosidase de mamífero ainda não foi estudada. Neste trabalho procurou-se estudar a ação de alguns novos compostos da família iminociclitol (figura 1) na atividade α-glucosidase de enterócitos de mamífero, tendo-se também avaliado o grau de toxidade. O efeito dos pares dos enantiómeros foi também estudado

Anti-proliferative effects of compounds derived from glucopyranuronamide

Chemotherapy is a major cancer treatment option. The synthesis of new compounds with better anti-proliferative properties and higher specificity is a current challenge in drug discovery today. Our goal with this work was to develop compounds derived from D-glucuronic acid and to evaluate their anti-proliferative properties. We have synthetized a library of hydroxyamide derivatives of D-glucuronic acid using amines and aminoalcohols. The synthesis of these compounds were based on the work of El-Nezhawy's group, who have designed some novel D-glucuronic acid acetylated and deacetylated derivatives, which showed interesting results with breast cancer cell lines. Anti-proliferative activity of the newly synthesized compounds was examined against human breast adenocarcinoma (MCF-7) and human colon carcinoma (MDST8) cell lines. Cell growth and viability was analysed by the Cell Counting Kit-8 method. The chemotherapeutic agent 5-fluoroacil was used as a positive control, allowing one to estimate the maximal anti-proliferative action expected in both carcinoma cell lines. All the compounds were studied in the 10-9-10-5M range. The compound N-(ethanol)-α/β D-glucopyranuronamide presented the best anti-proliferative potential with an IC50 (concentration of the compound causing 50% decrease in net cell growth) of 1.4x10-7M in MCF-7 cells. The 1-pheny-l-2-hydroxy-ethane-2-yl and the 1-propanol derivatives evoked weak anti-proliferative effects in MCF-7, with slight growth inhibition of 37% and 35%, respectively, for the highest concentration used (10-5M). On the contrary, the MDST-8 cell growth was not affected by these compounds. On the contrary, the 1-hydroxy-2-isopropyl-ethane-2-yl and 3-phenyl-1-hydroxy-propane-2-yl derivatives, exhibited weak anti-proliferative effects (22% and 40%, respectively) at 10-5M, in the MDST8 cell line, without affecting MCF-7 cell growth. None of the compounds exihibited toxic effects, at least up to 72h exposure, in the concentration range studied. These results show that the ethyl substituent was the most effective N-substituent for glucopyranuronamide for anti-proliferative actions in MCF-7 cell line, whilst in the case of the MDST8 cells, 3-phenyl-1-hydroxy-propane-2-yl was the most effective N-substituent. Moreover, all the glucopyranonamide compounds studied presented selective anti-proliferative effects for the different carcinoma cell lines used

3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: inhibition of rat intestinal α-glucosidase

Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 ± 0.046 and a KI of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ∼90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies

First insights into the diet composition of Madeiran and Monteiro’s storm petrels (Hydrobates castro and H. monteiroi) breeding in the Azores

Although studying the diet of threatened species is crucial in terms of conservation, the diet of the Madeiran Storm Petrel (Hydrobates castro) and the vulnerable, Azores-endemic Monteiro's Storm Petrel (H. monteiroi) is mostly unknown. The only information available to date comes from anecdotal observations, analysis of mercury levels and stable isotopes. Here is presented the first insights into prey consumption by adults and chicks from the two species breeding in the Azores Archipelago, Portugal, in the mid-Atlantic Ocean. The rapidly developing field of metabarcoding was used to identify dietary items from fecal samples, to species level where possible. A total of thirteen fish, five cephalopod, one crustacean and two oligochaete operational taxonomic units (OTUs) were detected. Results suggest that both petrel species feed mainly on myctophid fish. However, differences were detected between the prey species consumed by (i) H. monteiroi and H. castro, (ii) two distinct H. castro populations (Vila and Praia islets), and (iii) chicks and adults within the same population

Anti-proliferative effects of novel hydroxyamides and triazoles

Chemotherapy is a major cancer treatment option. The synthesis of new compounds with anti-proliferative properties and specificity is a current challenge in drug-discovery today. Our goal was to develop compounds, either hydroxyamides derived from D-glucuronic acid or triazole-cinchone hybrids, and to evaluate their anti-proliferative properties. Anti-proliferative activity of the newly synthesized compounds was examined against human breast adenocarcinoma (MCF-7) and human colon carcinoma (MDST8) cell-lines. Cell growth and viability was analysed by the Cell-Counting Kit-8 method. The 5-fluoroacil was used as a positive control. The compounds were studied between 10-9-10-5M. Fifteen compounds from the hydroxyamide family and two triazole compounds were investigated. Most of the compounds from the hydroxyamide family revealed mild (~20%) to moderate (50%) anti-proliferative effects in both cell-lines, with the exception of Hydroxyamide B1 which did not affect MDST8 proliferation, and hydroxyamide B3 where proliferation of MDST8 was inhibited by 90%. Triazoles (A and B) evoked a strong (~100%) anti-proliferative effect of MDST8 cell-lines. Proliferation of MCF-7 was selectively and effectively (~98%) inhibited by triazole B while triazole A had a mild effect. In conclusion, when compared to hydroxyamides, triazoles evoked a stronger anti-proliferative effect and might be promising anti-tumoral drugs

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and nonbreeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging speciespublishedVersio

The ARIA-MASK-air® approach

Funding Information: The authors thank Ms Véronique Pretschner for submitting the paper. MASK‐air has been supported by Charité Universitätsmedizin Berlin, EU grants (EU Structural and Development Funds Languedoc Roussillon and Region PACA; POLLAR: EIT Health; Twinning: EIP on AHA; Twinning DHE: H2020; Catalyse: Horizon Europe) and educational grants from Mylan‐Viatris, ALK, GSK, Novartis, Stallergènes‐Greer and Uriach. None for the study. ® Publisher Copyright: © 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.MASK-air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.publishersversionpublishe

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe