Determination of non-toxic and subtoxic concentrations of potential antiviral natural anthraquinones

Anthraquinones-rich extracts of Heterophyllaea pustulata Hook f. (Rubiaceae) exhibited in vitro antiviral activity against Herpes Simplex Virus Type I, from which several anthraquinones (AQs) were isolated and identified. The Maximum Non-Cytotoxic Concentration (MNCC), the subtoxic concentration (SubTC), and the CC50 of each AQ were determined on a mammalian eukaryotic cell line (Vero cells) by means of Neutral Red uptake assay; the cytopathic effect was simultaneously evaluated by optical microscopy. The range of concentrations where each AQ did not exhibit cytotoxicity was established, which is limited by the MNCC: rubiadin 1-methyl ether, damnacanthol and pustuline were found to be markedly less cytotoxic. To the remaining AQs, we could estimate a SubTC (about 10 μg/mL) that assures 80 % cellular viability. Therefore, we determined a concentration range which could be used to evaluate the antiviral effect of each AQ since it ensures the viability of the host cell.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Spontaneous photosensitization by Heterophyllaea pustulata Hook. f. (Rubiaceae), in sheep from Northwestern Argentina

Heterophyllaea pustulata Hook. f. (Rubiaceae) is a phototoxic plant. It grows in the Andean area of northwest of Argentina, and it causes significant economic losses in the livestock. This plant induces dermal lesions by photosensitization probably due to its content of photosensitizing anthraquinones. This paper describes an outbreak of poisoning in Corriedale sheepfold, which had an incidence of 49%. Ear skin biopsies and blood samples were collected of six affected animals. Liver enzymes remained within the reference limits. Histopathologically, a deep necrotizing dermatitis was identified in all samples. H. pustulata was identified in the areas of grazing. Anthraquinone concentration in leaves was 0.84% p/p, expressed as rubiadin. All findings allow us to conclude that the diagnosis is a primary photosensitization. Huge regional economic losses could be attributed to H. pustulata poisoning, although its toxicity has been little studied.Facultad de Ciencias Veterinaria

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Roadmap on printable electronic materials for next-generation sensors

The dissemination of sensors is key to realizing a sustainable, ‘intelligent’ world, where everyday objects and environments are equipped with sensing capabilities to advance the sustainability and quality of our lives—e.g., via smart homes, smart cities, smart healthcare, smart logistics, Industry 4.0, and precision agriculture. The realization of the full potential of these applications critically depends on the availability of easy-to-make, low-cost sensor technologies. Sensors based on printable electronic materials offer the ideal platform: they can be fabricated through simple methods (e.g., printing and coating) and are compatible with high-throughput roll-to-roll processing. Moreover, printable electronic materials often allow the fabrication of sensors on flexible/stretchable/biodegradable substrates, thereby enabling the deployment of sensors in unconventional settings. Fulfilling the promise of printable electronic materials for sensing will require materials and device innovations to enhance their ability to transduce external stimuli—light, ionizing radiation, pressure, strain, force, temperature, gas, vapours, humidity, and other chemical and biological analytes. This Roadmap brings together the viewpoints of experts in various printable sensing materials—and devices thereof—to provide insights into the status and outlook of the field. Alongside recent materials and device innovations, the roadmap discusses the key outstanding challenges pertaining to each printable sensing technology. Finally, the Roadmap points to promising directions to overcome these challenges and thus enable ubiquitous sensing for a sustainable, ‘intelligent’ world

El texto base como material didáctico del Sistema Educativo Bimodal de la UNPA

La sociedad del siglo XXI se ha visto marcada por la evolución que han tenido las Tecnologías de la Información y la Comunicación (TIC), aspecto que ha sido transversal a todos los ámbitos sociales y especialmente, al educativo. En este sentido, la Educación a Distancia mediada por las tecnologías se ha configurado como uno de los retos más importantes que nuestro país tiene en el marco de la Educación Superior. Numerosas son las instituciones educativas que se han acoplado a este nuevo desafío. Una de ellas es la Universidad Nacional de la Patagonia Austral (UNPA), organismo que desde el año 2004 ha comenzado a construir una alternativa en el proceso de enseñanza y aprendizaje a través de la creación del Sistema Educativo Bimodal. Bajo esta nueva relación pedagógica se acrecientan las posibilidades que fortalecen la aplicación de saberes a través diversos medios. Uno de ellos es el Texto Base, material didáctico por excelencia en la educación bimodal de la UNPA. El mismo favorece la comunicación y el aprendizaje en un alumno que estudia una carrera a distancia o un tramo de la misma. De esta manera, la UNPA fortalece los lazos que encaminan su política educativa hacia una universidad inclusiva.Red de Universidades con Carreras en Informática (RedUNCI

Partition coefficient (log P) determination of anthraquinone derivatives isolated from Heterophyllaea pustulata Hook. f. (Rubiaceae)

Las antraquinonas (AQs) aisladas de la especie fototóxica Heterophyllaea pustulata Hook. f. (Rubiáceas), soranjidiol, 1-metil éter de soranjidiol, rubiadina, 1-metil éter de rubiadina, damnacantal y damnacantol, son agentes fotosensibilizantes Tipo I y/o Tipo II. A su vez, presentan una potencial aplicación terapéutica debido a que extractos enriquecidos en las mismas y obtenidos a partir de hojas y tallos de H. pustulata, demostraron una importante actividad antibacteriana y antifúngica in vitro con baja toxicidad aguda in vivo. Con el fin de estimar la capacidad de estas AQs para ingresar y distribuirse en el organismo, atravesando membranas biológicas y así, poder desencadenar los efectos biológicos descriptos, se determinó el log P (expresión logarítmica de la lipofilicidad) de las mismas mediante el método de la ampolla. Con excepción de damnacantol, las AQs ensayadas presentaron un valor superior de log P en comparación a metoprolol. Además el valor promedio de log P para cada AQ fue comparable al valor obtenido mediante cálculos teóricos (CLogP).The anthraquinones isolated from the phototoxic species Hetero-phyllaea pustulata Hook. f. (Rubiáceas), soranjidiol, soranjidiol 1-methyl ether, rubiadin, rubiadin 1-methyl ether, damnacanthal and damnacanthol, are Type I and/or Type II photosensitizers. In addition, they show a potential therapeutic use according to results where extracts enriched in these metabolites and obtained from leaves and stems of H. pustulata demonstrated an important antibacterial and antifungal activity in vitro with a low acute toxicity in vivo. In order to estimate the capacity of these AQs to penetrate into the cells and their body distribution by going through biological membranes with the aim to unleash the described biological effects, we determinated the log P of each one by using the shake flash technique. Except for damnacanthol, all of the AQs tested showed a higher value of log P compared to metoprolol. In addition, the average value of log P for each AQ was similar to the theoretical value (CLogP).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Partition coefficient (log P) determination of anthraquinone derivatives isolated from Heterophyllaea pustulata Hook. f. (Rubiaceae)

Las antraquinonas (AQs) aisladas de la especie fototóxica Heterophyllaea pustulata Hook. f. (Rubiáceas), soranjidiol, 1-metil éter de soranjidiol, rubiadina, 1-metil éter de rubiadina, damnacantal y damnacantol, son agentes fotosensibilizantes Tipo I y/o Tipo II. A su vez, presentan una potencial aplicación terapéutica debido a que extractos enriquecidos en las mismas y obtenidos a partir de hojas y tallos de H. pustulata, demostraron una importante actividad antibacteriana y antifúngica in vitro con baja toxicidad aguda in vivo. Con el fin de estimar la capacidad de estas AQs para ingresar y distribuirse en el organismo, atravesando membranas biológicas y así, poder desencadenar los efectos biológicos descriptos, se determinó el log P (expresión logarítmica de la lipofilicidad) de las mismas mediante el método de la ampolla. Con excepción de damnacantol, las AQs ensayadas presentaron un valor superior de log P en comparación a metoprolol. Además el valor promedio de log P para cada AQ fue comparable al valor obtenido mediante cálculos teóricos (CLogP).The anthraquinones isolated from the phototoxic species Hetero-phyllaea pustulata Hook. f. (Rubiáceas), soranjidiol, soranjidiol 1-methyl ether, rubiadin, rubiadin 1-methyl ether, damnacanthal and damnacanthol, are Type I and/or Type II photosensitizers. In addition, they show a potential therapeutic use according to results where extracts enriched in these metabolites and obtained from leaves and stems of H. pustulata demonstrated an important antibacterial and antifungal activity in vitro with a low acute toxicity in vivo. In order to estimate the capacity of these AQs to penetrate into the cells and their body distribution by going through biological membranes with the aim to unleash the described biological effects, we determinated the log P of each one by using the shake flash technique. Except for damnacanthol, all of the AQs tested showed a higher value of log P compared to metoprolol. In addition, the average value of log P for each AQ was similar to the theoretical value (CLogP).Colegio de Farmacéuticos de la Provincia de Buenos Aire

La ubicuidad en la propuesta de Educación a Distancia de la UNPA

La Universidad Nacional de la Patagonia Austral, para dar respuesta a las demandas de educación superior en la región, ha incorporado un sistema de educación a distancia, el que ha ido evolucionando conforme el crecimiento de las necesidades institucionales y la aparición de herramientas más sofisticadas en el mercado. En este trabajo se detalla la incorporación de los sistemas de videoconferencias (sistema de videoconferencia punto a punto, y sistema de videoconferencia a través de Internet) al Sistema Educativo Bimodal de la UNPA, destacando aspectos funcionales, técnicos y operativos.Red de Universidades con Carreras en Informática (RedUNCI