Liquid chromatography method to assay tretinoin in skin layers : validation and application in skin penetration/retention studies

A liquid chromatography (LC) method for the quantification of tretinoin (TTN) in different matrices (adhesive tape, cotton and porcine skin layers, stratum corneum, viable epidermis, and dermis) was validated and applied in in vitro porcine skin penetration/retention studies. This study proposes, for the first time, a method for assaying TTN in separated porcine skin layers (stratum corneum, viable epidermis, and dermis). The skin studies were carried out using tape stripping and cutaneous retention techniques. The procedures for the extraction of TTN from dermatological formulations (creams and gels) and biological and non-biological matrices used with the tape stripping and retention techniques were also evaluated. The LC method consisted of a mobile phase composed of a mixture of methanol, water, and glacial acetic acid (85:15:1, v/v); a C18 column used as the stationary phase; a flow rate of 1.0 mL min 1; an injection volume of 100 μL; and TTN detection at 342 nm. The method was linear in the range of 0.05–15.00 μg mL 1 (r ¼ 0.9999), and it was precise and accurate. The limit of detection (LOD) and limit of quantification (LOQ) were 0.0165 μg mL 1 and 0.0495 μg mL 1, respectively. TTN was extracted from different matrices, showing good precision [relative standard deviation (RSD) of <5%] and accuracy (89.4–113.9%). This method was successfully applied in the evaluation of TTN skin retention/permeation from dermatological formulations (cream and gel). A higher penetration of TTN through the skin was achieved with the gel rather than the cream, showing the influence of the dosage form. Therefore, the developed method can easily be applied in porcine skin penetration/retention studies of dermatological formulations containing TTN, and it is able to discriminate the behaviours of the different formulations

12,500+ and counting: biodiversity of the Brazilian Pampa

Knowledge on biodiversity is fundamental for conservation strategies. The Brazilian Pampa region, located in subtropical southern Brazil, is neglected in terms of conservation, and knowledge of its biodiversity is fragmented. We aim to answer the question: how many, and which, species occur in the Brazilian Pampa? In a collaborative effort, we built species lists for plants, animals, bacteria, and fungi that occur in the Brazilian Pampa. We included information on distribution patterns, main habitat types, and conservation status. Our study resulted in referenced lists totaling 12,503 species (12,854 taxa, when considering infraspecific taxonomic categories [or units]). Vascular plants amount to 3,642 species (including 165 Pteridophytes), while algae have 2,046 species (2,378 taxa) and bryophytes 316 species (318 taxa). Fungi (incl. lichenized fungi) contains 1,141 species (1,144 taxa). Animals total 5,358 species (5,372 taxa). Among the latter, vertebrates comprise 1,136 species, while invertebrates are represented by 4,222 species. Our data indicate that, according to current knowledge, the Pampa holds approximately 9% of the Brazilian biodiversity in an area of little more than 2% of Brazil’s total land The proportion of species restricted to the Brazilian Pampa is low (with few groups as exceptions), as it is part of a larger grassland ecoregion and in a transitional climatic setting. Our study yielded considerably higher species numbers than previously known for many species groups; for some, it provides the first published compilation. Further efforts are needed to increase knowledge in the Pampa and other regions of Brazil. Considering the strategic importance of biodiversity and its conservation, appropriate government policies are needed to fund studies on biodiversity, create accessible and constantly updated biodiversity databases, and consider biodiversity in school curricula and other outreach activitie

Nomenclature, Diagnosis and Management of Drug-induced Autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report.

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarizes the major topics discussed at a joint International Conference held between Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and often resolve spontaneously after stopping the culprit drug whereas patients with AIH mostly need long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements such as Khat and Tinospora cordifolia have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow a precise diagnosis and similarly, there is no single feature which is diagnostic of AIH. A management algorithm is proposed. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterization of this condition

Nomenclature, Diagnosis and Management of Drug-induced Autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarizes the major topics discussed at a joint International Conference held between Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and often resolve spontaneously after stopping the culprit drug whereas patients with AIH mostly need long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements such as Khat and Tinospora cordifolia have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow a precise diagnosis and similarly, there is no single feature which is diagnostic of AIH. A management algorithm is proposed. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterization of this condition

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Proyecto, investigación e innovación en urbanismo, arquitectura y diseño industrial

Actas de congresoLas VII Jornadas de Investigación “Encuentro y Reflexión” y I Jornadas de Investigación de becarios y doctorandos. Proyecto, investigación e innovación en Urbanismo, Arquitectura y Diseño Industrial se centraron en cuatro ejes: el proyecto; la dimensión tecnológica y la gestión; la dimensión social y cultural y la enseñanza en Arquitectura, Urbanismo y Diseño Industrial, sustentados en las líneas prioritarias de investigación definidas epistemológicamente en el Consejo Asesor de Ciencia y Tecnología de esta Universidad Nacional de Córdoba. Con el objetivo de afianzar continuidad, formación y transferencia de métodos, metodología y recursos se incorporó becarios y doctorandos de los Institutos de investigación. La Comisión Honoraria la integraron las tres Secretarias de Investigación de la Facultad, arquitectas Marta Polo, quien fundó y María del Carmen Franchello y Nora Gutiérrez Crespo quienes continuaron la tradición de la buena práctica del debate en la cotidianeidad de la propia Facultad. Los textos que conforman las VII Jornadas son los avances y resultados de las investigaciones realizadas en el bienio 2016-2018.Fil: Novello, María Alejandra. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Repiso, Luciana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Mir, Guillermo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Brizuela, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Herrera, Fernanda. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Períes, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Romo, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Gordillo, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Andrade, Elena Beatriz. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentin

Lipid-core nanocapsules: cutaneous penetration studies and proposition of strategies to assess the in vitro drug release

Neste trabalho foi avaliada a permeação/penetração cutânea in vitro (pele suína) de propionato de clobetasol nanoencapsulado incorporado em um semissólido, empregando células de difusão de Franz. A nanoencapsulação foi capaz de reduzir a quantidade de fármaco que penetra nas camadas da pele (estrato córneo, epiderme e derme) sem alterar a forma (distribuição percentual) como o propionato de clobetasol se distribui. A adequabilidade de diferentes membranas sintéticas (acetato de celulose, policarbonato e membrana de diálise) para a avaliação da liberação in vitro, empregando células de difusão de Franz, a partir desta formulação foi também estudada. A partir da combinação de diferentes técnicas analíticas (espalhamento de luz dinâmica, microscopias eletrônicas de transmissão e varredura) foi observado que a membrana de menor tamanho de poro (membrana de diálise, 12 kDa de cut off) é a mais adequada para a condução deste tipo de avaliação, pois é a única capaz de evitar a passagem de nanocápsulas íntegras da formulação para o meio receptor das células de difusão, em detrimento das membranas de policarbonato e acetato de celulose (0,05 μm e 0,45 μm de tamanho de poro, respectivamente). Além disso, uma nova estratégia para a avaliação da liberação in vitro de fármacos associados a nanocápsulas de núcleo lipídico, combinando fluxo contínuo de meio de liberação e sacos de diálise foi proposta neste trabalho. A técnica mostrou-se adequada para a obtenção do perfil de liberação in vitro a partir de suspensões de nanocápsulas contendo diferentes fármacos modelo (prednisolona e propionato de clobetasol), possibilitando a diferenciação destes sistemas de soluções contendo os fármacos livres, graficamente e pelos valores de fluxo calculados. Adicionalmente, esta estratégia mostrou-se apropriada para a manutenção da concentração de fármaco no meio de liberação afastada da saturação, contribuindo para o atendimento da condição sink. Ainda, classificamos o sistema como um protótipo semi-automatizado para a avaliação da liberação in vitro de fármacos, capaz de gerar resultados com maior precisão em relação à diálise convencional.The in vitro cutaneous permeation/penetration (porcine skin) of clobetasol propionate-loaded lipid-core nanocapsules incorporated into a semisolid dosage form was evaluated, using the Franz diffusion cells technique. It was shown that the nanoencapsulation was able to reduce the drug amount penetration into skin layers (stratum corneum, epidermis and dermis) without changing the way (percentual distribution) that it was distributed. The suitability of different synthetic membranes (cellulose acetate, polycarbonate, and dialysis membrane) to assess the in vitro drug release using Franz diffusion cells from this formulation was also studied. It was ascertained by combining different analytical techniques (dynamic light scattering, scanning and transmition electron microscopy) that the membrane with smaller pore size (dialysis membrane, 12 kDa cut off) is the most appropriate for conducting this kind of study, because it is the only one able of preventing the passage of intact nanocapsules from formulation to Franz diffusion cells receptor media, instead of polycarbonate and cellulose acetate membranes (0.05 and 0.45 pore size, respectively). In addition, a new strategy to assess in vitro drug release drug-loaded lipid-core nanocapsules was proposed, associating continuous flow of release media and dialysis sac. The proposed system was adequate to assess the in vitro drug release profiles from nanocapsule suspensions containing different model drugs (prednisolone and clobetasol propionate), enabling the differentiation of these systems from drug solutions, graphically and by the calculated flux values. Furthermore, this strategy was suitable to maintain the drug concentration into release media far away from saturation, contributing to the sink condition. Also, the proposed system was described as a semi-automated prototype for in vitro drug release evaluation, able to produce results with greater accuracy than conventional dialysis technique

Lipid-core nanocapsules: cutaneous penetration studies and proposition of strategies to assess the in vitro drug release

Neste trabalho foi avaliada a permeação/penetração cutânea in vitro (pele suína) de propionato de clobetasol nanoencapsulado incorporado em um semissólido, empregando células de difusão de Franz. A nanoencapsulação foi capaz de reduzir a quantidade de fármaco que penetra nas camadas da pele (estrato córneo, epiderme e derme) sem alterar a forma (distribuição percentual) como o propionato de clobetasol se distribui. A adequabilidade de diferentes membranas sintéticas (acetato de celulose, policarbonato e membrana de diálise) para a avaliação da liberação in vitro, empregando células de difusão de Franz, a partir desta formulação foi também estudada. A partir da combinação de diferentes técnicas analíticas (espalhamento de luz dinâmica, microscopias eletrônicas de transmissão e varredura) foi observado que a membrana de menor tamanho de poro (membrana de diálise, 12 kDa de cut off) é a mais adequada para a condução deste tipo de avaliação, pois é a única capaz de evitar a passagem de nanocápsulas íntegras da formulação para o meio receptor das células de difusão, em detrimento das membranas de policarbonato e acetato de celulose (0,05 μm e 0,45 μm de tamanho de poro, respectivamente). Além disso, uma nova estratégia para a avaliação da liberação in vitro de fármacos associados a nanocápsulas de núcleo lipídico, combinando fluxo contínuo de meio de liberação e sacos de diálise foi proposta neste trabalho. A técnica mostrou-se adequada para a obtenção do perfil de liberação in vitro a partir de suspensões de nanocápsulas contendo diferentes fármacos modelo (prednisolona e propionato de clobetasol), possibilitando a diferenciação destes sistemas de soluções contendo os fármacos livres, graficamente e pelos valores de fluxo calculados. Adicionalmente, esta estratégia mostrou-se apropriada para a manutenção da concentração de fármaco no meio de liberação afastada da saturação, contribuindo para o atendimento da condição sink. Ainda, classificamos o sistema como um protótipo semi-automatizado para a avaliação da liberação in vitro de fármacos, capaz de gerar resultados com maior precisão em relação à diálise convencional.The in vitro cutaneous permeation/penetration (porcine skin) of clobetasol propionate-loaded lipid-core nanocapsules incorporated into a semisolid dosage form was evaluated, using the Franz diffusion cells technique. It was shown that the nanoencapsulation was able to reduce the drug amount penetration into skin layers (stratum corneum, epidermis and dermis) without changing the way (percentual distribution) that it was distributed. The suitability of different synthetic membranes (cellulose acetate, polycarbonate, and dialysis membrane) to assess the in vitro drug release using Franz diffusion cells from this formulation was also studied. It was ascertained by combining different analytical techniques (dynamic light scattering, scanning and transmition electron microscopy) that the membrane with smaller pore size (dialysis membrane, 12 kDa cut off) is the most appropriate for conducting this kind of study, because it is the only one able of preventing the passage of intact nanocapsules from formulation to Franz diffusion cells receptor media, instead of polycarbonate and cellulose acetate membranes (0.05 and 0.45 pore size, respectively). In addition, a new strategy to assess in vitro drug release drug-loaded lipid-core nanocapsules was proposed, associating continuous flow of release media and dialysis sac. The proposed system was adequate to assess the in vitro drug release profiles from nanocapsule suspensions containing different model drugs (prednisolone and clobetasol propionate), enabling the differentiation of these systems from drug solutions, graphically and by the calculated flux values. Furthermore, this strategy was suitable to maintain the drug concentration into release media far away from saturation, contributing to the sink condition. Also, the proposed system was described as a semi-automated prototype for in vitro drug release evaluation, able to produce results with greater accuracy than conventional dialysis technique