Covid-19: Vacina boa é a aplicada de forma adequada / Covid-19: Vacina boa é a aplicada de forma adequada

Na atualidade, fotografar ou gravar o instante da imunização contra a Covid-19 se tornou rotina compartilhada nas redes sociais. Essa exposição instigou a observação de uma questão relevante: a técnica de aplicação está correta? Com a veiculação de imagens, é possível visualizar as vacinas sendo administradas em diferentes áreas do músculo deltoide, o que pode acarretar efeitos adversos. A otimização da qualificação técnica e pedagógica dos profissionais que elaboram e ministram as capacitações, bem como o envolvimento efetivo dos vacinadores nos treinamentos para injeção intramuscular é uma necessidade constante para evitar mais danos à saúde da população

Currently, photographing or recording the instant of immunization against Covid-19 has become a shared routine on social networks. This exposition prompted the observation of a relevant question: is the application technique correct? With the transmission of images, it is possible to visualize the vaccines being administered in different areas of the deltoid muscle, which can cause adverse effects. The optimization of the technical and pedagogical qualification of the professionals who design and deliver the training, as well as the effective involvement of vaccinators in training for intramuscular injection, is a constant need to avoid further damage to the health of the population

Otimização de método extrativo para raízes de Arctium lappa L / Extractive method optimization for Arctium lappa l. Roots / Optimización de un método de extracción de raíces de Arctium lappa L

Arctium lappa L. é indicada no Formulário de Fitoterápicos da Farmacopeia Brasileira para o tratamento de distúrbios urinários leves. Estudos já demonstraram o potencial antioxidante, anti-inflamatório e antidiabético deste extrato, onde foram identificados fenóis, lignanas, taninos e flavonoides. O objetivo deste trabalho foi otimizar o método extrativo de raízes de A. lappa. Realizou-se o preparo de extratos por diferentes métodos: Ultrassom, Soxhlet, maceração e turbo extração. A otimização foi realizada por turbo extração seguindo um planejamento fatorial 23, empregando como fatores: teor alcoólico, concentração da matéria prima e tempo de extração. Os extratos foram avaliados quanto ao resíduo seco, teores de fenóis e flavonoides, e atividade antioxidante. Com relação ao resíduo seco, e aos teores de fenóis e flavonoides, os métodos de ultrassom e turbo extração demonstraram melhor poder extrativo. Devido ao menor tempo e custo operacional, a otimização foi realizada por turbo extração, e o extrato otimizado foi obtido utilizando álcool 60%, em proporção matéria prima solvente 1:10 e tempo de extração de 15 minutos. Estas análises poderão nortear futuros testes de transposição de método para escala industrial, diminuindo mão de obra, tempo e custos, visando obter produtos fitoterápicos mais eficientes, com valor acessível à população.

Arctium lappa L. is indicated in the Brazilian Pharmacopeia Herbal Medicines Form for the treatment of mild urinary disorders. Studies have already demonstrated the antioxidant, anti-inflammatory and antidiabetic potential of this extract, where phenols, lignans, tannins and flavonoids were identified. The objective of this work was to optimize the extractive method of A. lappa roots. Extracts were prepared by different methods: Ultrasound, Soxhlet, maceration and vortical extraction. The optimization was performed by vortical extraction following a 23 full factorial design, using as factors: alcohol content, drug concentration and extraction time. The extracts were evaluated for dry residue, phenols and flavonoids contents, and antioxidant activity. Regarding the dry residue, and the phenols and flavonoids contents, the ultrasound and vortical extraction methods showed better extractive power. Due to the lower operating time and cost, the optimization was performed by vortical extraction, and the optimized extract was obtained using 60% alcohol, in a 1:10 drug solvent ratio and extraction time of 15 minutes. These assessments guide the future tests of transposition of the method to an industrial scale, reducing manpower, time and costs, aiming to obtain more efficient phytotherapic products, with affordable value for the population.

Arctium lappa L. está indicado en la Formulacao de Fitoterápicos da Farmacopeia Brasileira para el tratamiento de trastornos urinarios leves. Los estudios han demostrado el potencial antioxidante, antiinflamatorio y antidiabético de este extracto, donde se identificaron fenoles, lignanos, taninos y flavonoides. El objetivo de este trabajo fue optimizar el método extractivo de las raíces de A. lappa. Los extractos se prepararon por diferentes métodos: Ultrasonido, Soxhlet, maceración y turboextracción. La optimización se realizó mediante turboextracción siguiendo una planificación factorial de 23, empleando como factores: tenor alcohólico, concentración de materia prima y tiempo de extracción. Se evaluaron los extractos para determinar el residuo seco, el contenido de fenoles y flavonoides y la actividad antioxidante. En cuanto al contenido de residuo seco, fenoles y flavonoides, los métodos de extracción por ultrasonidos y turbo demostraron un mejor poder de extracción. Debido al menor tiempo y coste operativo, la optimización se realizó mediante turboextracción, y el extracto optimizado se obtuvo utilizando alcohol 60%, en proporción disolvente-materia 1:10 y tiempo de extracción de 15 minutos. Estos análisis podrán orientar futuros ensayos de transposición del método para escala industrial, reduciendo mano de obra, tiempo y costes, con el objetivo de obtener productos fitoterapéuticos más eficientes, con valor accesible para la población.

Bioprocess optimization of interferon ß-1-a in Pichia pastoris and its improved inhibitory effect against hepatocellular carcinoma cells

Interferon-ß-1a (INF-ß-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-ß-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-ß- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-ß-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-ß-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- ß-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO

Optimization of expression yield in a stable cell line expressing a novel mutated chimeric tissue plasminogen activator (mt-PA)

Abstract The development of stable cell lines producing recombinant proteins is very time-consuming and laborious. One of the practical approaches successfully performed is Fluorescence-Activated Cell Sorting (FACS). A mutated chimeric tissue plasminogen activator (mt-PA) was developed by removing the first three domains of t-PA, insertion of GHRP sequence and mutation toward resistance to plasminogen activator inhibitor-1 (PAI-1). In the current study, a new stable CHO-DG44 cell line producing mt-PA was developed by two sequential clonal selections: FACS and clonal-selection by limiting dilution. Furthermore, the expression was more evaluated using two different expression media. Finally, the high-producing clones were selected based on the dot blot and amidolytic activity test. The transfection efficiency of CHO-DG44 cells was 38% as measured by flow cytometry on green fluorescent protein (GFP). After performing FACS on stable cell pools, the expression yield was increased to fifty-fold. In terms of growth profile, CD-DG44 showed higher viability and cell density results than ProCHO5 medium. The expression of mt-PA was significantly higher in CD-DG44 than in ProCHO5, 765 and 280 IU/mL, respectively. Our data indicated that selection of an appropriate expression medium played a critical role in the development of potent producing stable cells by FACS.

Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

Novel biopharmaceutical development investigations towards drug and formulation performance optimization

For a drug to excerpt pharmacological action after oral intake, it first needs to be released from the formulation, get into solution (dissolve), be absorbed, and reach the systemic circulation. Since only solubilized drugs can be absorbed, and thus have therapeutic effect, the understanding of the dissolution and drug release processes of a drug product is of primary importance. Such understanding allows a robust formulation development with an ideal in vivo performance. In order to meet set standards, the performance assessment of oral drug products, such as dissolution testing, often applies conditions that are not reflective of the in vivo environment. The use of non-physiologically relevant dissolution method during the drug product development phase can be misleading and give poor mechanistic understanding of the in vivo dissolution process. Hence, we hypothesized that applying physiologically relevant conditions to the dissolution test would result in more accurate in vivo predictability for a robust and precise development process. Since the buffering system in the intestinal lumen operates at low molarity values, phosphate buffer at low buffer capacity was used as a first approach to an in vivo relevant parameter. Furthermore, a biphasic system was used, that is, the low buffer capacity medium was paired with an organic layer (n-octanol) to mimic the concurrent drug absorption that happens with the in vivo dissolution. Both poorly and highly soluble drugs in immediate release formulations (ibuprofen and metronidazole, respectively) were tested in this set-up to assess the dissolution in the aqueous medium and the partitioning to the organic phase. Additionally, enteric coated formulations were tested in bicarbonate buffer at the in vivo reported molarities values to assess the impact of buffer species on drug dissolution. The evaluated parameters were the buffer system (bicarbonate buffer vs. phosphate buffer), buffer capacity and medium pH. In all approaches, dissolution was also carried out in compendial buffer for comparison purposes. Our results demonstrate that the USP-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied noncompendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating drug release with improved physiological relevance. Similarly, all the enteric coated formulations displayed a fast release in phosphate buffer and complied with the compendial performance specifications. On the other hand, they all had a much slower drug release in bicarbonate buffer and failed the USP acceptance criteria. Also, the nature of the drug (acid vs base) impacted the dissolution behavior in bicarbonate buffer. This study indicates that compendial dissolution test for enteric coated tablets lacks physiological relevance and it needs to be reevaluated. Thus, an in vivo relevant performance method for EC products is needed. Overall, the findings of this thesis comprehensively demonstrates that meaningful differences in performance and accordance to clinical reports were only obtained when physiological relevant conditions were applied. Hence, our results indicate that the central hypothesis was answered positively

Para que um medicamento exerça a ação farmacológica após a ingestão oral, ele primeiro precisa ser liberado da formulação, dissolver, ser absorvido e atingir a circulação sistêmica. Uma vez que apenas medicamentos solubilizados podem ser absorvidos e, assim, ter efeito terapêutico, a compreensão dos processos de dissolução e liberação de um medicamento é de extrema importância. Tal compreensão permite o desenvolvimento de uma formulação robusta com o desempenho in vivo ideal. Para atender aos padrões regulatórios previamente estabelecidos, a avaliação da performance de formulações orais, como por exemplo, o teste de dissolução, frequentemente aplica condições que não refletem o ambiente fisiológico. O uso de métodos de dissolução não fisiologicamente relevante durante a fase de desenvolvimento do medicamento pode gerar resultados equivocados sem uma compreensão mecanistica do processo de dissolução in vivo. Portanto, a hipótese desse trabalho é que a aplicação de condições fisiologicamente relevantes no teste de dissolução resultaria em uma predição mais precisa da dissolução in vivo para um processo de desenvolvimento robusto e preciso. Uma vez que o sistema tampão no lúmen intestinal possui baixa molaridade, o tampão fosfato com baixa capacidade tamponante foi usado como uma primeira abordagem como um meio de dissolução fisiologicamente relevante. Além disso, foi utilizado um sistema bifásico, ou seja, o meio de baixa capacidade tamponante combinado a uma fase orgânica (n-octanol) para imitar a absorção in vivo. Formulações de liberação imediata contendo fármacos de baixa e de alta solubilidade (ibuprofeno e metronidazol, respectivamente) foram testadas no sistema bifásico para avaliar a dissolução no meio aquoso e a partição para a fase orgânica. Ademais, formulações com revestimento entérico foram testadas em tampão bicarbonato nos valores de molaridades fisiológicos para avaliar o impacto da espécie tamponante na dissolução do fármaco. Os parâmetros avaliados foram o sistema tampão (tampão bicarbonato vs. tampão fosfato), capacidade tamponante e pH médio. Em todas as abordagens, a dissolução também foi realizada em tampão farmacopeico para fins de comparação. Nossos resultados demonstraram que o método de dissolução farmacopeico não foi discriminativo, enquanto o meio com menor capacidade tamponante diferenciou entre as formulações obtidas via granulação úmida ou compressão direta. Ademais, a utilização da fase orgânica no teste de dissolução bifásica auxiliou no controle do pH do meio aquoso. Portanto, os métodos não compendiais aplicados foram mais discriminativos do que as condições de dissolução convencionais. Neste estudo, foi demonstrado como a dissolução bifásica e uma baixa capacidade tamponante podem ser usadas para avaliar as diferenças na performance de formulações. Esta pode ser uma abordagem valiosa durante os estágios iniciais do desenvolvimento de medicamentos para investigar a liberação destes sob condições fisiologicamente relevantes. Da mesma forma, todas as formulações com revestimento entérico exibiram uma liberação rápida em tampão de fosfato e atenderam às especificações farmacopeicas. Entretanto, a liberação do fármaco foi muito mais lenta em tampão de bicarbonato e consequentemente não cumpriram com as especificações farmacopeicas. Além disso, a natureza do fármaco (ácido vs. base) impactou o comportamento de dissolução no tampão de bicarbonato. Este estudo indica que o teste de dissolução convencional para comprimidos de liberação retardada não possui relevância fisiológica e precisa ser reavaliado. Portanto, os resultados desta tese demonstram de forma abrangente que diferenças significativas na performance condizentes com relatórios clínicos foram obtidas apenas quando as condições fisiológicas relevantes foram aplicadas. Esses resultados indicam que a hipótese central foi respondida positivamente

Aplicação da eletroforese capilar - espectrometria de massas para identificação dos produtos de degradação do aripiprazol em medicamentos / Application of capillary electrophoresis - mass spectrometry to identify aripiprazole degradation products in drugs

Diretrizes internacionais e nacionais como a FDA (Food and Drug Administration), ICH (International Council for Harmonisation) e ANVISA (Agência Nacional de Vigilância Sanitária) estabelecem a exigência de testes de estabilidade para entender melhor a qualidade de um medicamento. O estudo de estabilidade deve ser realizado usando métodos indicativos de estabilidade que possam qualificar e quantificar os insumos farmacêuticos do medicamento, bem como as impurezas e produtos de degradação nele contidos. O aripiprazol é um antipsicótico atípico de segunda geração aprovado para o tratamento de esquizofrenia, transtorno bipolar, depressão e transtornos do espectro do autismo. Os métodos oficiais descritos nas farmacopeias para avaliar o aripiprazol e suas impurezas utilizam a cromatografia líquida de alta eficiência (HPLC) como técnica principal. Nesta pesquisa, objetivou-se desenvolver um método indicativo de estabilidade por eletroforese capilar de zona (CZE) para o aripiprazol na forma farmacêutica de comprimidos, e identificação dos produtos de degradação por espectrometria de massas. O estudo de degradação forçada e a optimização do método desenvolvido por CZE foram realizados utilizando o conceito de delineamento de experimentos (DoE). A separação do aripiprazol de seus produtos de degradação foi conseguida usando uma coluna capilar de sílica fundida (30,2 cm x 75 µm ID), eletrólito de formiato de amônio 6 mmol/L (pH 3) com 5% de metanol sob um potencial de 15 kV e detecção em 214 nm. A capacidade indicativa de estabilidade do método foi investigada pela análise do aripiprazol após ser submetido a condições de estresse ácido, alcalino, térmico, fotolítico e oxidativo, de acordo com as diretrizes ICH. A oxidação foi a principal via de degradação entre as condições de estresse avaliadas. O aripiprazol foi separado dos seus produtos de degradação oxidativa em tempo de corrida abaixo de 5 minutos. O método por CZE mostrou ser linear na faixa de 60 - 140 µg/mL, R2 = 0,9980, precisão calculada como desvio padrão relativo (DPR) menor que 2% e exatidão calculada como recuperação média de 100,93 ± 0,77%. Os resultados obtidos demonstram que o método por HPLC-RP em modo gradiente, separou o aripiprazol e seus produtos de degradação em um tempo de corrida de 30 minutos. Quatro produtos de degradação foram detectados pelo método LC-MS e o principal produto de degradação oxidativo foi identificado. O aripiprazol mostrou-se suscetível à oxidação no grupo piperazina, gerando principalmente o composto aripiprazol-1-N-óxido

International and national guidelines such as the FDA (Food and Drug Administration), ICH (International Council for Harmonization) and ANVISA (National Health Surveillance Agency) establish the requirement for stability tests to better understand quality of a medicine. The stability study must be carried out using stability indicating methods that can qualify and quantify the pharmaceutical ingredients of the drug, as well as the impurities and degradation products contained therein. Aripiprazole is a second-generation atypic antipsychotic drug approved for the treatment of schizophrenia, bipolar disorder, depression, and autism spectrum disorders. The official method described in the pharmacopoeias to evaluate aripiprazole and its impurities is high performance liquid chromatography (HPLC) as the main technique. In this research, the objective was to develop an indicative method of stability by capillary zone electrophoresis (CZE) for aripiprazole in the pharmaceutical form of tablets, and identification of degradation products by mass spectrometry. The forced degradation study and the optimization of the method developed by CZE were carried out using the concept of design of experiments (DoE). The separation of aripiprazole from its degradation products was achieved using a fused silica capillary column (30,2 cm x 75 µm ID), 6 mmol/L ammonium formate electrolyte (pH 3) with 5% methanol under a potential of 15 kV and detection at 214 nm. The indicative stability of the method was investigated by analyzing aripiprazole after being subjected to acid, alkali, thermal, photolytic and oxidative stress conditions, according to the ICH guidelines. Oxidation was the main degradation pathway among the stress conditions evaluated. Aripiprazole was separated from its oxidative degradation products at run times below 5 minutes. The CZE method proved to be linear in the range of 60 - 140 µg/mL, R2 = 0,9980, precision calculated as a relative standard deviation (DPR) of less than 2% and accuracy calculated as a mean recovery of 100,93 ± 0,77%. The results obtained demonstrate that the HPLC-RP method in gradient mode separated aripiprazole and its degradation products in a run time of 30 minutes. Four degradation products were detected by the LC-MS method and the main oxidative degradation product was identified. Aripiprazole was shown to be susceptible to oxidation in the piperazine group, generating mainly the compound aripiprazole-1-N-oxide

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Moviéndonos hacia la Urología Híbrida / Moving Towards Hybrid Urology

"Cogito ergo sum" la famosa frase de René Descartes tendría que replantearse hoy como "decido, luego existo". La inteligencia natural es esencialmente una batalla de la racionalidad contra el sesgo y el ruido, la vida finalmente se trata de una suma de decisiones. La medicina no es ajena a este conflicto; es una ciencia humana que gravita sobre la incertidumbre y por ello quienes la ejercemos debemos considerar el fallo como un potencial desenlace, pero el fenómeno de la ilusión terapéutica algunas veces produce un efecto cegador que perpetúa nuestro sesgo. La promesa de disminuir este potencial riesgo en las decisiones y la optimización consecuente en los procesos humanos es lo que dio origen al desarrollo al que llamamos "inteligencia artificial".

"Cogito ergo sum" the famous phrase of René Descartes would have to be rephrased today as "I decide, therefore I am". Natural intelligence is essentially a battle of rationality against bias and noise; life is ultimately a sum of decisions. Medicine is no stranger to this conflict; it is a human science that gravitates on uncertainty and therefore those of us who practice it must consider failure as a potential outcome, but the phenomenon of therapeutic illusion sometimes produces a blinding effect that perpetuates our bias. The promise of reducing this potential risk in decisions and the consequent optimization of human processes is what gave rise to the development we call "artificial intelligence".

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Renovación y trasformación / Renewal and transformation

Los cambios que se realizan en cualquier aspecto de la vida son necesarios, transforman la imagen y revitalizan. La mayoría de los cambios conllevan a renovación. Todos los animales se renuevan, las aves pierden sus plumas y reaparecen otras, más vivas, sanas, coloridas y de mejor brillo. Los mamíferos recambian solo su pelaje, algunos de manera estival y muchos de ellos acomodando su color al entorno. El más conocido y evidente es el de los reptiles, las serpientes realizan un proceso biológico complejo que implica aumento de secreciones tipo linfa debajo de la piel antigua que le ayuda a cambiar paulatinamente a su nueva piel. Todos estos cambios son necesarios y revitalizan, dan lozanía y mejoran el estado de ánimo. La SCCOT y la RCCOT han decidido hacer algunos cambios.

Optimization of glycerol-based medium composition for antifungal metabolites production by Bacillus subtilis

Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.

Optimización de la protección en radiología y cardiología intervencionista pediatrica en América Latina y el Caribe (OPRIPALC) / Optimization of protection in pediatric interventional cardiology and radiology in Latin America and the Caribbean (OPRIPALC)

El objetivo del presente artículo ha sido describir el programa "Optimización de la Protección en Radiología Intervencionista Pediátrica en América Latina y el Caribe" (OPRIPALC) que nace el año 2018 como respuesta conjunta de la Organización Panamericana de la Salud y la Organización Mundial de la Salud, en cooperación con el Organismo Internacional de Energía Atómica, para colaborar con sus Estados miembros en asegurar que las exposiciones a la radiación de los pacientes pediátricos sean las mínimas necesarias durante los procedimientos intervencionistas. Actualmente, hay 18 centros de los siguientes 10 países que participan: Argentina, Brasil, Chile, Colombia, Costa Rica, Cuba, Ecuador, México, Perú y Uruguay. Para el desarrollo del programa se plantean una serie de objetivos, productos, actividades y resultados esperados. La puesta en marcha de la WEB de OPRIPALC ha significado un instrumento muy válido para seguir la información actualizada del programa. Un programa actualizado de formación en radioprotección para los profesionales implicados en el programa, se está realizando por medio de "webinars". Se deberá seguir actuando en la aplicación del programa de control de calidad básico para los equipos de rayos X participantes y validar los valores de los Niveles de Referencia para Diagnóstico (NRDs). Se propone formar un equipo de trabajo entre los Físicos Médicos y Tecnólogos Médicos participantes de OPRIPALC para implicarse en las pruebas de control básicas que todos los centros debieran realizar. Se han presentado algunos resultados iniciales de OPRIPALC en eventos científicos internacionales. Se está avanzando en proponer unos primeros valores sobre NRDs en procedimientos de intervencionismo cardiológico pediátrico por bandas de edad y peso. OPRIPALC es una de las pocas iniciativas de carácter regional para obtener valores de NRDs en procedimientos intervencionistas pediátricos. Se espera que tanto los valores de referencia como la metodología empleada en OPRIPALC, puedan ser utilizados en otras regiones del mundo.

The objective of this article has been to describe the program "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) that was born in 2018 as a joint response of the Pan American Health Organization and the World Organization of the Health, in cooperation with the International Atomic Energy Agency, to collaborate with its member states in ensuring that radiation exposures of pediatric patients are the minimum necessary during interventional procedures. Currently, there are 18 centers from the following 10 countries participating: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico, Peru and Uruguay. For the development of the program, a series of objectives, products, activities and expected results are proposed. The launch of the OPRIPALC WEBSITE has been a very valid instrument for following up-to-date information on the program. An updated training program in radiation protection for the professionals involved in the program is being carried out through webinars. It should continue acting in the application of the basic quality control program for the participating X-ray equipment and validate the values of the Diagnostic Reference Levels (DRLs). It is proposed to form a work team among the OPRIPALC participating medical physicists to get involved in the basic control tests that all centers should carry out. Some initial results of OPRIPALC have been presented at international scientific events. Progress is being made in proposing first values on DRLs in pediatric cardiac intervention procedures by age and weight bands. OPRIPALC is one of the few regional initiatives to obtain DRLs values in pediatric interventional procedures. It is expected that both the reference values and the methodology used in OPRIPALC can be used in other regions of the world.

Lean: Introduction of a Quality Improvement Concept into Percutaneous Nephrolithotomy to Improve Efficiency while Maintaining Safety / Lean: introducción de un concepto en la nefrolitotomía percutánea para mejorar la eficiencia mientras se mantiene la seguridad

Introduction and objective Standardization of surgical interventions reduces complications and costs and positively impacts intra and postoperative outcomes. Implementation of the lean concept, initially proposed in the auto industry, now becomes an interesting approach in the surgical setting. We want to present the results of how percutaneous nephrolithotripsy (PCNL) in a high-level center can be positively impacted by implementing the lean concept. Methods We evaluated a total of 140 PCNL procedures. Group 1 included all cases operated prior to implementing the lean concept and group 2 was composed of those operated after implementing the lean concept. We looked for all seven sources of waste to identify and modify our practice to improve efficiency and safety. We then collected intraoperative times and compared the ones prior to those after the implementation. Results After implementing the lean concept, with an average of six PCNL cases per day, a comparison was made to an equivalent number of cases prior to the lean implementation (group 1). The average total operative time for PCNL preintervention was 138 (confidence interval [CI]: 79 to 170) minutes and postlean intervention was 71.1 (CI: 43 to 157) minutes. Surgical time (cystoscopy to skin closure) was 36.1 (CI: 25 to 50) minutes prelean and 50 minutes postlean (CI: 23 to 154). For this last one, bilateral procedures were performed. Operative room turnover time was 27.8 (CI: 21 to 38) minutes prelean and 5.67 (CI: 3.5 to 12) minutes postlean. Induction time was 16.5 (CI: 5 to 55) minutes prelean and 5.4 (CI: 3.5 to 7.5) minutes postlean. Conclusion Implementation of the lean concept enables optimization of the surgical procedure, allowing hospitals to reduce costs and standardization.

Introducción y objetivo La estandarización de los procedimientos quirúrgicos reduce complicaciones, costos, y mejora resultados intra y postoperatorios. El concepto lean fue utilizado por primera vez en la industria automotriz. El presente trabajo busca implementar el concepto lean para optimizar el procedimiento de nefrolitotomía percutánea (NLP) en nuestro medio. Métodos Se realizaron 140 procedimientos de nefrolitotomía percutánea, los cuales se dividieron en 2 grupos: uno en el cual se registraron los tiempos intraoperatorios, y el segundo en que se registraron los tiempos luego de la implementación del concepto lean. Resultados Durante el período estudiado, se realizaron 70 procedimientos luego de la implementación del concepto lean, y se logró realizar un promedio de 6 procedimientos por día. Se compararon los tiempos operatorios, y se encontró un tiempo operatorio total promedio de 138 (intervalo de confianza [IC]: 79 a 170) minutos pre-lean, y de 71,1 (IC: 43 a 157) minutos post-lean. El tiempo quirúrgico (cistoscopia a cierre de piel) pre-lean fue de 36,1 (IC: 25 a 50) minutos, y el post-lean fue de 50 (IC: 23 a 154) minutos. Para este último, se trató de procedimientos bilaterales. El cambio de sala fue de 27,8 (IC: 21a 38) minutos pre-lean, y de 5,67 (IC: 3.5 a 12) minutos post-lean. El tiempo de inducción fue de 16.5 (IC: 5 a 55) minutos pre-lean, y de 5.4 (IC: 3.5 a 7.5) minutos post-lean. Conclusiones La implementación del concepto lean permite optimizar el procedimiento, con reducción de costos y estandarización del modelo de atención para cualquier centro asistencial. La movilización de los especialistas en nuestro modelo de atención permite un mayor cubrimiento poblacional de alta calidad.

Optimization of energy consumption per kg of pure meat by electrical and thermal systems in broiler chicken farms / [Otimização do consumo de energia por kg de carne pura por meio de sistemas térmicos em granjas de frangos de corte]

The present study was conducted to investigate the effect of electrical and thermal systems optimization on energy consumption in broiler farms. Experiments were conducted in 4 different climates (cold, hot, dry, and temperate) with four treatments (4 broiler farms in each region) and 5 iterations (5 rearing periods per farm) on the Ross 308 strain of broiler chicken in a completely randomized basic design. The results showed that the solutions applied in cold and dry climates had a significant effect on reducing energy consumption (P<0.05). In the hot climate, although the reduction in energy consumption was observed after the application of the solutions, the difference was not statistically significant (P>0.05). Also, the application of solutions in temperate climates created a significant difference in the specific amount of thermal energy consumption per kilo of meat and total energy (P<0.05). Overall, the results of the present experiment showed that optimizing the electrical and thermal systems of broiler houses could reduce energy consumption in all climates.(AU)

O presente estudo foi realizado para investigar o efeito da otimização de sistemas elétricos e térmicos no consumo de energia em fazendas de frangos de corte. Foram realizadas experiências em 4 climas diferentes (frio, quente, seco e temperado) com quatro tratamentos (4 granjas de frangos de corte em cada região) e 5 iterações (5 períodos de criação por granja) na cepa Ross 308 de frangos de corte em um projeto básico completamente aleatório. Os resultados mostraram que as soluções aplicadas em climas frios e secos tiveram um efeito significativo na redução do consumo de energia (P<0,05). No clima quente, embora a redução no consumo de energia tenha sido observada após a aplicação das soluções, a diferença não foi estatisticamente significativa (P>0,05). Além disso, a aplicação de soluções em climas temperados criou uma diferença significativa na quantidade específica de consumo de energia térmica por quilo de carne e energia total (P<0,05). Em geral, os resultados do presente experimento mostraram que a otimização dos sistemas elétricos e térmicos das casas de frangos de corte poderia reduzir o consumo de energia em todos os climas.(AU)

Módulo Cartas Avales para el Sistema Informático Colpadi de la Unidad Central de Cooperación Médica. Cuba / Module Letters Guarantees for the Colpadi Computer System of the Central Unit for Medical Cooperation. Cuba

La Unidad Central de Cooperación Médica (UCCM) es un centro de excelencia del Ministerio de Salud Pública (MINSAP). Este centro se encarga de garantizar el cumplimiento de los compromisos internacionales contraídos por el MINSAP y el Gobierno de la República de Cuba, en el área de la cooperación médica a través de la asistencia técnica y docente. El objetivo de este desarrollo es implementar un módulo para el Sistema Integral para la Gestión de Información en la Colaboración Médica Cubana (Colpadi), que optimice el proceso de gestión de cartas avales que se generan en la UCCM. El trabajo que se desarrolla contribuye de forma positiva al concepto de excelencia de la institución. El proyecto tiene un enfoque cualitativo, con alcance descriptivo, de tipo retrospectivo y diseño no experimental, de corte transversal. Se emplean los métodos científicos de observación y análisis documental. Además, la implementación utilizando el Lenguaje Unificado de Modelado (UML) y la metodología RUP de desarrollo de software. Como resultado se obtiene un módulo, como parte del sistema informático Colpadi, que optimiza el proceso de gestión de cartas avales. Las cartas avales se entregan a los cooperantes internacionalistas del MINSAP en sus vacaciones y al finalizar su misión en el exterior. Con la implementación de la aplicación informática se obtienen varias ventajas como la automatización de los vuelos de entrada, las solicitudes automáticas para el procesamiento de las cartas avales, los reportes estadísticos y el tratamiento de la información(AU)

Central Unit for Medical Cooperation (UCCM) is a center of excellence of the Ministry of Public Health (MINSAP). This center is in charge for guaranteeing compliance with the international commitments made by MINSAP and the Government of the Republic of Cuba, in the area of ​​medical cooperation through technical and educational assistance. This research contributes positively to the institution's concept of excellence. Its objective is to implement a module for the Colpadi computer system, which it optimizes the process for managing the guarantee letters generated at the UCCM. The research has a qualitative approach, with a descriptive scope, of a retrospective type and a non-experimental, cross-sectional design. Scientific observation and documentary analysis methods are used; as well as UML, and RUP software development methodology in its implementation. As a result, a module is obtained, as part of the Colpadi computer system, which it optimizes the guarantee letter management process. The letters of guarantee are delivered to the internationalist aid workers of the MINSAP, on their vacations and at the end of their mission abroad. With the implementation of the computer application, several advantages are obtained, such as the automation of the incoming flights, the automatic requests for the processing of the letters of guarantee, the statistical reports and the treatment of the information(AU)

Recuperación mejorada después de la cirugía: un cambio de paradigma en cuidados peri operatorios. Artículo de revisión / Enchanced recovery after surgry: a paradigm shift in perioperative care. Review article

La recuperación mejorada después de la cirugía (ERAS®) es un protocolo multimodal aplicado a la atención peri operatoria. Estos protocolos están implementados por un equipo multidisciplinario centrado en el paciente, incorporan personal clínico ambulatorio, enfermeras, anestesiólogos, personal de recuperación post operatoria, personal de nutrición, fisioterapeutas, trabajadores sociales y cirujanos. Independientemente de la subespecialidad quirúrgica, todos los protocolos ERAS® comparten los mismos objetivos: optimización pre operatoria del paciente, disminución del estrés peri operatorio, mantenimiento de la función fisiológica post operatoria y tiempo de recuperación acelerado después de la cirugía. Los protocolos ERAS® están diseñados para reducir la respuesta al estrés quirúrgico, facilitar el mantenimiento de la composición corporal y función orgánica para lograr una recuperación temprana(AU)

Enhanced Recovery After Surgery (ERAS®) is a multimodal protocol applied to perioperative care. These protocols are implemented by a multidisciplinary patient-centered team, incorporating outpatient clinical staff, nurses, anesthesiologists, post-operative recovery staff, nutrition staff, physical therapists, social workers, and surgeons. Regardless of the surgical subspecialty, all ERAS® protocols share the same objectives: preoperative optimization of the patient, reduction of perioperative stress, maintenance of post-operative physiological function, and accelerated recovery time after surgery. ERAS® protocols are designed to reduce the response to surgical stress, facilitate the maintenance of body composition and organ function to achieve early recovery(AU)

Manual para otimização da aquisição de medicamentos no âmbito hospitalar / Manual for optimizing the acquisition of medicines in the hospital environment

Introdução: a falta de um medicamento durante a internação hospitalar, põe em risco o correto cumprimento dos planos terapêuticos traçados para os pacientes, o que pode vir a gerar a recidiva de um quadro clínico, o prolongamento do tempo de internação e o consequente aumento de custos para a instituição, seja ela pública ou privada. Dentro da cadeia logística do medicamento, diversas são as etapas que podem contribuir para o desabastecimento. No âmbito hospitalar essa logística se dá por meio do ciclo da assistência farmacêutica que compreende as etapas de seleção, programação, aquisição, armazenamento, distribuição e dispensação de medicamentos. Os estoques da farmácia hospitalar são caracterizados por ciclos de demandas e de ressuprimentos, com flutuações significativas, o que dificulta a disponibilidade na mesma proporção da utilização do medicamento. Tendo em vista esta complexidade torna-se necessário o uso de indicadores, que avaliem os processos de trabalho. Objetivos: o objetivo deste estudo foi identificar as principais causas de desabastecimento de medicamentos em uma unidade de saúde e desenvolver um manual para otimização da aquisição de medicamentos. Materiais e método: Inicialmente foi realizado um mapeamento do fluxo de valor a fim de compreender a movimentação de materiais e informações envolvidos no processo de aquisição de medicamentos. Posteriormente, confeccionou-se uma planilha para registrar o fluxo logístico dos produtos, que resultou na obtenção dos pontos críticos do processo. A coleta dos dados de aquisição de medicamentos foi realizada durante o ano de 2019. Os critérios avaliados foram definidos com base nas ocorrências que mais contribuíram para o desabastecimento, seja pela relevância, ou pela frequência. Por fim foi elaborado um manual contendo critérios, normas, e procedimentos, a serem seguidos a fim de se evitar o desabastecimento. Resultados: Elaboração de um manual para otimização da aquisição de medicamentos composto por: mapa do fluxo de valor logístico de medicamentos, planilha para registro da logística de aquisição de medicamentos, procedimentos operacionais padrão para a gestão da aquisição de medicamentos. Conclusão: com o manual espera-se otimizar a gestão logística de medicamentos e reduzir a incidência de problemas com desabastecimento, gerando um impacto positivo na assistência ao paciente

Introduction: the lack of a drug during hospitalization puts at risk the correct compliance with the therapeutic plans outlined for the patients, which can lead to the recurrence of a clinical condition, the extension of the hospital stay and the consequent increase in costs for the institution, whether public or private. Within the drug's logistics chain, there are several steps that can contribute to shortages. In the hospital context, this logistics takes place through the pharmaceutical care cycle, which comprises the stages of selection, programming, acquisition, storage, distribution and dispensing of medicines. Hospital pharmacy stocks are characterized by cycles of demand and resupply, with significant fluctuations, which makes availability in the same proportion as the use of the medication difficult. Due to this complexity, it is necessary to use indicators that assess work processes. Objectives: The aim of this study was to identify the main causes of drug shortages in a health unit and to develop a manual for optimizing drug acquisition. Materials and method: Initially, a mapping of the value stream was carried out in order to understand the flow of materials and information involved in the drug procurement process. Subsequently, a spreadsheet was made to record the logistical flow of the products, which resulted in the critical points of the process being obtained. Logistic data for drug acquisition during 2019 were collected and the criteria evaluated were defined based on the occurrences that most contributed to the shortage, either by relevance or by the frequency with which they occurred. Finally, a manual was created containing criteria, norms, and procedures to be followed in order to avoid shortages. Results: Preparation of a manual for optimizing drug procurement, comprising: a map of the logistical value flow of drugs, a spreadsheet for recording the logistics of drug procurement, standard operating procedures for managing drug procurement. Conclusion: the manual is expected to optimize the logistical management of medicines and reduce the incidence of problems with shortages, generating a positive impact on patient care

Isolation and characterization of antihypertensive peptides from soy bean protein

Proteins and peptides are the most diverse biomolecules found in nature and make our interest due to their wide applications in food and pharmaceutical industry. Angiotensin Converting Enzyme (ACE) plays a major role in controlling blood pressure. The inhibition of ACE with peptides is a main target in the regulation of hypertension. The objective of the present study was to investigate the therapeutic potential of soy bean. This was accomplished by isolation of ACE inhibitory peptides using response surface methodology (RSM) and characterization of these bioactive peptides by mass spectrometry. 31 hydrolyzed fractions were isolated and evaluated for their ACE inhibition potential. Hydrolyzed fraction having highest ACE inhibitory activity was characterized by liquid chromatography-mass spectrometry (LC-MS) technique. RSM results showed maximum ACE inhibition potential (64%) by hydrolyzate was obtained at 45 ºC temperature, pH 8.0, E/S 0.2 in 2 hours hydrolysis time. Results of LC-MS analysis revealed Ser-Gly, Ser-Pro, Met-Ala, His-Ala, Lys-Pro, Phe-Thr, Met-Leu, Pro-Arg, Ala-Pro-Val, Pro-Ala-Leu, Val-Met-Gly, Pro-Leu-Val, Pro-Pro-Gln, His-Arg-Gly, Ser-Phe-Val-Leu, Ala-Val-His-Try, Arg-Thr-Val-Arg, His-His-Tyr-Leu-Val, Asp-Gly-Ala-Cys-Ser-Ala-Asn and MetVal-Thr-Gly-Pro-Gly-Cys-His bioactive peptides in hydrolyzed fraction of soy bean. Our data provide evidence that response surface methodology is a good approach for isolation of antihypertensive bioactive peptides with more potent activity as nutraceuticals or pharmaceuticals. Therefore soy bean can be use for industrial production of pharmaceutical grade natural medicines for handling high blood pressure.