Parsley Leaves (Petroselinum Sativum) as Corrosion Inhibitors of Steel DIN 2391 St 37-4 in Acid Medium 5% H2SO4

In this article, the corrosion inhibition of steel DIN 2391 St 37-4 in acidic medium 5% H2SO4 with and without the presence of eco inhibitors of leaf (Petroselinum Sativum) was examined. Inhibitory properties of parsley leaves (Petroselinum Sativum) on steel DIN 2391 St 37-4 were examined by potentiodynamic polarization - Tafel extrapolation, and FTIR method in order to categorize the oxide layer. The test was performed in static medium and with stirring at 600 rpm. By Tafel extrapolation based on changes in corrosion potential, the inhibitor behaves as mixed. Increasing the concentration of inhibitors increases the efficiency of inhibition. Corrosion processes are inhibited by adsorption of organic matter on the surface of steel DIN 2391 St 37-4, forming a film. The obtained results indicate that parsley leaf (Petroselinum Sativum) is an effective eco inhibitor for the tested steel in 5% sulfuric acid.

A Universal Key to Rationally Select Which, Among Nonparametric Species Richness Estimators, Performs Best According to Each Particular Incomplete Sampling

Since most samplings of local species communities are bound to remain substantially incomplete for practical reasons, a wide variety of nonparametric estimators of the number of unrecorded species have been proposed over the past fifty years. Unfortunately, the distinct formulations of each of these estimators naturally lead to substantially divergent estimates. The will to try to select, in each case, the estimator expected to be the more accurate has long been carried out only on a purely empirical, even arbitrary, basis (as is evident from the extensive consultation of much of the past literature on estimating species richness of incompletely sampled communities). So that extrapolating the true species richness of a community from its incomplete survey has long remained quite unsatisfactory. Indeed, the definition of a truly rational procedure for selecting the most accurate (least-biased) estimator actually requires a solidly established theoretical framework, involving to conform, as best as possible, to the general mathematical characteristics of the Species Accumulation Function. Accordingly, unveiling, first of all, these mathematical characteristics of the Species Accumulation Function was a decisive step forward in this perspective. Thereby making it now possible to propose an objective key to rationally select the one, within the series of various estimators, which, depending on each particular sampling, happens to be the least biased in this particular case, thus providing the most accurate estimate of the number of still unrecorded species. And, consequently, making it possible, now, to deliver the best estimate of the true species richness of a local community, despite its being incompletely surveyed.

Prediction of the bioequivalence of different crystal forms of rifampicin based on physiologically based pharmacokinetic model / 中国药科大学学报

@#The physiologically based pharmacokinetic (PBPK) modeling strategy was adopted to predict the pharmacokinetic behavior of crystal forms I and II of rifampicin in humans, which was used to determine whether the two were bioequivalent.After conducting studies in vitro of the two crystal forms, a rat PBPK model was established based on the pharmacokinetic data of intravenous administration in rats.The model was optimized by the pharmacokinetic data of oral administration in rats.Species were extrapolated to healthy humans, and the extrapolation model was used to predict such pharmacokinetic behaviors as the drug-time curve, absorption site, and absorption amount of the two crystal forms of rifampicin in healthy humans.The prediction results of the healthy human model showed that the cmax of form I and form II rifampicin were 8.42 and 10.35 μg/mL, tmax were 0.40 and 0.32 h,and AUC0-t were both 62.90 μg·h/mL.According to the prediction results of absorption, neither crystal form I nor crystal form II rifampicin was absorbed in the stomach, yet both were completely absorbed in the intestinal tract, with both the absorption site and the absorption amount were basically the same.The pharmacokinetic parameters of both crystal forms I and II of rifampicin were very close, which could indicate bioequivalence.

Diversidad y estructura arbórea en afloramientos de carbonato de calcio en Calakmul, México / Tree diversity and structure in carbonate calcium banks in Calakmul, Mexico

Resumen Introducción: La vegetación arbórea de selvas que se desarrolla en ambientes kársticos dominados por carbonato de calcio enfrenta la restricción de agua y nutrientes, lo que condiciona su desarrollo. Objetivo: Analizar la composición, diversidad y estructura de la vegetación arbórea que se desarrolla en afloramientos de calcio (yesales) y sus condiciones edáficas comparándolas con las presentes en vegetación secundaria (VS). Métodos: Se emplearon 17 parcelas de 1 000 m², 14 en yesales y 3 en VS. Se obtuvo una muestra compuesta de suelo por parcela y estimamos pH, conductividad eléctrica (CE-salinidad), % de carbonatos de calcio (CaCO3), materia orgánica (MO), fósforo (P) y nitrógeno (N). La diferencia en la composición de especies se evaluó mediante un análisis de similitud (ANOSIM). Empleamos métodos de rarefacción y extrapolación, estimando la diversidad mediante los números de Hill (q = 0, q = 1 y q = 2). Se utilizó un análisis de regresión linear para evaluar la influencia de las características edáficas en la diversidad, el diámetro y la altura promedios. Resultados: Los suelos en yesales presentaron concentraciones bajas de MO, P y N, valores altos de CE-salinidad y altos porcentajes de CaCO3. Se registraron 6 443 individuos de 54 especies en yesales y 594 individuos de 62 especies en la VS, siendo la composición significativamente diferente. La diversidad, los valores promedio de altura y diámetro fueron menores en yesales respecto de VS, estas diferencias estuvieron relacionadas con las condiciones edáficas. Conclusiones: La vegetación arbórea en yesales tiene una composición semejante a la de selvas subperennifolias de Calakmul. Las tallas pequeñas de los árboles están relacionadas con el alto porcentaje de CaCO3 y los altos valores de CE que condicionan la disponibilidad de MO, N y P. Este estudio apoya la idea de que precarias condiciones edáficas tienen una influencia negativa en la diversidad y la estructura horizontal y vertical de la vegetación arbórea.

Abstract Introduction: Tree vegetation of forests that develops in karst environments dominated by calcium carbonate faces the restriction of water and nutrients, which negatively affects its development. Objective: Analyze the composition, diversity, and structure of tree vegetation that develops in calcium outcrops (yesales) and their edaphic conditions compared to those present in the adjacent secondary vegetation (VS). Methods: Plots of 1 000 m² were used, 14 in yesales and 3 in VS. For soil sampling, we obtained a sample composed of each plot, and estimate pH, electrical conductivity (EC-salinity), % of calcium carbonates (CaCO3), organic matter (OM), phosphorus (P) and nitrogen content (N). The difference in species composition was estimated by similarity analysis (ANOSIM). We used rarefaction and extrapolation methods to standardize sample, and estimate diversity by Hill numbers (q = 0, q = 1 and q = 2). Linear regression was used to determine the relative influence of edaphic characteristics in diversity, average diameter, and height. Results: Soils in yesales presented low concentrations of OM, P, and N, with high values of EC-salinity and high percentages of CaCO3. In yesales, 6 443 individuals were recorded in 54 species and in the secondary vegetation 594 individuals and 62 species, the species composition being significantly different between both conditions. Diversity, average values of height, and diameter were significantly lower in yesales regarding the secondary vegetation, these differences were significantly related to edaphic conditions. Conclusions: Tree vegetation in yesales has a composition like the sub-evergreen forests of Calakmul. Small sizes in the arboreal individuals are related to the high percentage of CaCO3 and the high EC values, which partly condition the low availability of OM, N and P affecting the growth of the trees. This study supports the idea that precarious edaphic conditions have a negative influence on the diversity and horizontal and vertical structure of tree vegetation.

One extraction tool for in vitro-in vivo extrapolation?SPME-based metabolomics of in vitro 2D,3D,and in vivo mouse melanoma models / 药物分析学报

Solid phase microextraction(SPME)in combination with high-resolution mass spectrometry was employed for the determination of metabolomic profile of mouse melanoma growth within in vitro 2D,in vitro 3D,and in vivo models.Such multi-model approach had never been investigated before.Due to the low-invasiveness of SPME,it was possible to perform time-course analysis,which allowed building time profile of biochemical reactions in the studied material.Such approach does not require the multiplication of samples as subsequent analyses are performed from the very same cell culture or from the same individual.SPME already reduces the number of animals required for experiment;therefore,it is with good concordance with the 3Rs rule(replacement,reduction,and refinement).Among tested models,the largest number of compounds was found within the in vitro 2D cell culture model,while in vivo and in vitro 3D models had the lowest number of detected compounds.These results may be connected with a higher metabolic rate,as well as lower integrity of the in vitro 2D model compared to the in vitro 3D model resulting in a lower number of compounds released into medium in the latter model.In terms of in vitro-in vivo extrapolation,the in vitro 2D model performed more similar to in vivo model compared to in vitro 3D model;however,it might have been due to the fact that only compounds secreted to medium were investigated.Thus,in further experiments to obtain full metabolome infor-mation,the intraspheroidal assessment or spheroid dissociation would be necessary.

Comparative Study on Regulatory Measures of Biosimilars in China ，the United States ，Japan and Europe / 中国药房

OBJECTIVE：To provi de reference for drug admini stration supervision of biosimilars in China. METHODS ： Referring to the authoritative documents of the official websites of National Medical Products Administration of China ，FDA of the United States ，European Drug A dministration and Japan ’s D rug and M edical Devices Agency ，and comparing their regulatory measures on the definition ，effectiveness，safety and clinical application of biosimilars，the suggestions were put forward for the improvement of regulatory measures of biosimilars in China. RESULTS & CONCLUSIONS ：Although the definitions biosimilars in different countries/regions were different ，they all required that biosimilars should have the same drug quality ，safety and effectiveness as their corresponding reference drugs. The United States ，the European Union and Japan required enterprises to provide studies on the similarity of early pharmacy ，non-clinical studies such as pharmacology and toxicology ，and clinical studies on immunogenicity ，pharmacokinetics and pharmacodynamics of biosimilars and reference drugs. However ，the similarity between biosimilars and reference drugs had not been required in China. All countries/regions supported the extrapolation of indications of biosimilars. Among which the United States and the European Union required manufacturers to provide detailed data ；Japan only mentioned the relevant concepts of indications extrapolation of biosimilars，but did not mention the specific data requirements. The relevant description of the conditions for the extrapolation of biosimilars in China was not clear enough ，and its application in China was still facing great challenges. In terms of drug interchangeability ，although the United States allowed the use of interchangeable biosimilars to replace reference drugs under the conditions permitted by state laws ，no relevant biosimilars had been approved；European countries had different regulations on the interchangeability of biosimilars；but there was no document explicitly mentioned in China and Japan on the interchangeability of biosimilars. It is suggested that the principle of comparison should be further improved and strict requirements should be appropriately enforced in ensuring the effectiveness and safety of biosimilars；in the field of indication extrapolation ，more detailed data requirements should be put forward ，and the possible risks after extrapolation should be evaluated scientifically ；in terms of the interchangeability of biosimilars ，it is suggested to try to implement the principle of conversion of biosimilars ，but it should be used after consultation among doctors ，pharmacists and patients，and drug use safety should be monitored timely. Meanwhile ，a sound traceability system should be established to ensure drug safety of patients.

Analysis of the current situation of road traffic accidents in the 31 provinces/municipalities of China and the projection for achieving the SDGs target of halving the numbers of death and injury / 中华疾病控制杂志

Objective To analyze the data of road traffic accidents, deaths and injuries in 31 provinces and municipalities in China from 2010 to 2017, and to predict that the number of deaths and injuries caused by road accidents set in the sustainable development goals (SDGs) will be halved by 2020 compared with the target set in 2015. Methods Describing and analyzing the current situation of road traffic accidents in 31 provinces and municipalities in China, and using the trend extrapolation method to predict whether the SDGs target can be achieved by 2020. Results The numbers of traffic accidents, deaths and injuries in Guangdong, Jiangsu, Zhejiang and Shandong Provinces showed a downward trend from 2010 to 2017, but still ranked the front in China. In 2017, Beijing had the highest death rate followed by Guizhou as the second, and Guizhou had the highest injury rate followed by Tianjin as the second. The projected results showed that the numbers of deaths and injuries caused by road traffic accidents in China would be increased by 17% and 1.3% respectively in 2020 indicating that SDGs target could not be met. Among the 31 provinces/municipalities, it was predicted that the numbers of deaths and injuries in Hunan would be reduced to 50.7% and 65.3% in 2015, respectively by 2020, and the target could be achieved; the number of injuries in Shanghai was decreased by 83.3%, but the deaths was only decreased by 34.5%, and there was still a gap with the target; the rest 29 provinces/municipalities could not meet SDGs target. It was expected that the deaths in 11 provinces and municipalities would increase by 2020, with Beijing, Jilin, Jiangxi, Hubei and Guizhou Provinces showing the most significant growth. The number of injured people in 8 provinces and municipalities shows an increasing trend, with Jilin, Jiangxi, Hubei and Guizhou provinces showing significant growth. Conclusions Except for Hunan Province, it was difficult for the whole country and the rest provinces and municipalities to reach the SDGs target. According to the forecast results and the actual situation, a targeted scientific prevention and control strategy can be formulated. The measures taken by Hunan and Shanghai in traffic accident prevention and control were effective and worth learning.

Prueba de caminata de seis minutos ¿es posible predecir el consumo de oxígeno en personas con patologías? Una revisión bibliográfica / Six-Minute Walk Test. Is It Possible to Predict Oxygen Consumption in People with Pathologies? A Bibliographic Review / Teste de caminhada seis minutos. É possível prever o consumo de oxigênio em pessoas com patologia? Uma revisão bibliográfica

Resumen La prueba de caminata de seis minutos (PC6M) consiste en recorrer la mayor distancia posible y se caracteriza por ser una prueba de fácil realización. El objetivo de esta revisión fue examinar la relación entre las variables de distancia recorrida, patologías cardíacas, pulmonares y el consumo de oxígeno de una prueba de criterio en cinta rodante y/o cicloergómetro, y las ecuaciones de predicción del VO2 en la PC6M de Maldonado e Ingle (2006), Vanhelst (2013) y Costa (2017) para personas con patologías. El manuscrito es una revisión bibliográfica que utilizó las bases de datos Scopus y WOS, con artículos en inglés, español y portugués entre 2000 y 2017. La distancia es la variable que más se midió y que más se asoció con el VO2, encontrándose correlaciones significativas con valores de 0.01 hasta 0.8, las patologías más relacionadas con el VO2 máx. fueron la hipertensión pulmonar, enfermedad pulmonar obstructiva, insuficiencia cardíaca, disfunción sistólica ventricular y accidente cerebro-vascular y el cicloergómetro fue el más utilizado en las pruebas de criterio de VO2 máx. Solo una ecuación fue elaborada para niños que eran obesos la que incluyó distancia e IMC (Vanhelst), otra ecuación fue para adultos con enfermedad cardíaca que además incluía el sexo (Costa), una en pacientes con disfunción sistólica ventricular que aparte incorporó la edad, volumen espiratorio y hemoglobina (Ingle) y otra fórmula fue para adultos con insuficiencia cardíaca que consideró la distancia (Maldonado). Se sugiere utilizar la ecuación más apropiada y elaborar modelos predictivos para personas con diversas características.

Abstract The six-minute walk test (SMWT) consists of walking as far as possible and is characterized by being an easy test to perform. This paper examines the relationship between the variables of distance traveled, cardiac and pulmonary pathologies, and the oxygen consumption of a criterion test on treadmill and/or cycle ergometer, and the prediction equations of VO2 in the SMWT of Maldonado and Ingle (2006), Vanhelst (2013) and Costa (2017) for people with pathologies. The paper is a bibliographic review that used the Scopus and WOS databases containing articles in English, Spanish and Portuguese, published between 2000 and 2017. Distance is the variable that was most measured, and it was most associated with VO2; correlations with values from 0.01 to 0.8 were found. The pathologies most related to VO2 max were pulmonary hypertension, obstructive pulmonary disease, and ventricular heart failure and stroke; and the cycle ergometer was the most commonly used in the VO2 max criterion tests. Only one equation was created for children who were obese; it included distance and BMI (Vanhelst). Another equation was generated for adults with heart disease that also included sex (Costa). Besides, one equation was for patients with ventricular systolic dysfunction that also incorporated age, volume expiratory and hemoglobin (Ingle); another one was created for adults with heart failure, and this formula considered the distance (Maldonado). It is suggested to use the most appropriate equation and create predictive models for people with different characteristics.

Resumo O teste de caminhada de seis minutos (TC6M) consiste em andar o mais longe possível e é caracterizado como um teste fácil. O objetivo desta revisão foi examinar a relação entre as variáveis distância percorrida, patologias cardíacas, pulmonares e o consumo de oxigênio de um teste de critério em esteira e/ou ciclo ergômetro, e as equações de predição do VO 2 no TC6M de Maldonado e Ingle (2006), Vanhelst (2013) e Costa (2017) para pessoas com patologias. O manuscrito é uma revisão bibliográfica que utilizou as bases de dados Scopus e WOS, com artigos em inglês, espanhol e português entre 2000 e 2017. A distância é a variável mais medida e mais associada ao VO 2, encontrando correlações significativas com valores de 0,01 a 0,8, as patologias mais relacionadas ao VO 2 max. foram a hipertensão pulmonar, doença pulmonar obstrutiva, insuficiência cardíaca, disfunção sistólica ventricular e acidente vascular encefálico e o ciclo ergômetro foi o mais utilizado nos testes do critério VO 2 max. Apenas uma equação foi desenvolvida para crianças obesas, que incluíram distância e IMC (Vanhelst), outra equação foi para adultos com doença cardíaca que também incluiu sexo (Coast), uma em pacientes com disfunção sistólica ventricular que incorporaram a idade, volume expiratório e hemoglobina (Ingle) e outra fórmula foi para adultos com insuficiência cardíaca que considerou a distância (Maldonado). Sugere-se utilizar a equação mais adequada e desenvolver modelos preditivos para pessoas com características diversas.

Influence of Fishing Activity on Total Species Richness and Abundance Unevenness in Reef Fish Communities: A Case Study in a Brazilian Tropical Coral Complex

The internal organization of reef-fish communities, particularly the species richness and the hierarchical structuring of species abundances, depends on many environmental factors, including fishing intensity and proportion of macroalgal cover which are expected to have determinant influences. However, reported studies on this topic are generally based on incomplete samplings (almost unavoidable in practice when dealing with highly uneven and species-rich communities), so that the derived results can be appreciably skewed. To overcome this difficulty, the incomplete samplings involved in this study were completed numerically through a reliable extrapolation procedure. This precaution provided a safe confirmation that reduced fishing activity and increased macroalgae cover both contribute to enhance the total species richness and to reduce the abundance unevenness in these reef fish communities. Yet, it is shown that this reduction of abundance unevenness is almost entirely attributable to the increase in species richness.

The Exploration of Extrapolation of Data from Adults to Pediatric Population / 中国医疗器械杂志

Pediatric medical devices cannot meet the existing medical needs now. In consideration of the difficulty that clinical trials conducted in pediatric population, reasonable extrapolation of adult device data to pediatric population can maximize the use of existing data, as well as reduce unnecessary clinical trials in pediatric populations. It can also help accelerate the development and marketing of pediatric medical devices and ensure the clinical demand of pediatric devices. We analyzed the related guiding principles in America, and explored the extrapolation of medical device data to pediatric population in China from the perspective of medical device technology evaluation, hoping to provide reference in promoting China's data extrapolation.

El papel de los biosimilares en la enfermedad inflamatoria intestinal: una realidad en nuestro país / The Role of Biosimilars in Inflammatory Bowel Disease: A Reality in our Country

Resumen La enfermedad inflamatoria intestinal (EII) es un término con el que se conocen varias entidades, las 2 más importantes son: la colitis ulcerativa idiopática (CUI) y la enfermedad de Crohn (EC), cuyo origen es multifactorial y se caracterizan por un fenómeno inflamatorio, crónico, recurrente con diferentes grados de severidad del tubo digestivo; pero además con afectación potencial de otros órganos. En la última década ha habido un renovado interés en dichas entidades, debido a una incidencia creciente de estas, pero también debido al desarrollo de medicamentos que por primera vez están cambiando la historia natural de estas enfermedades: son los medicamentos llamados biológicos, que son aquellos producidos o derivados de organismos vivos y representan el sector de mayor crecimiento en la industria farmacéutica mundial. Debido al interés comercial, se han desarrollado y sometido a las autoridades reguladoras productos no originadores; similares, pero no idénticos a los productos de referencia. La Agencia Europea de Medicamentos (EMA) aprobó el primer biosimilar del infliximab para todas las indicaciones en las cuales este estaba aprobado, incluidas: colitis ulcerativa moderada a severa en todas las edades, EC moderada a severa en todas las edades, al igual que EC fistulizante, artritis psoriásica (AP), psoriasis, espondilitis anquilosante (EA) y artritis reumatoide (AR) (1). En esta revisión nos proponemos definir lo que son estos productos al igual que algunos conceptos relacionados (extrapolación, sustitución e intercambiabilidad), además hacer una revisión histórica de su desarrollo, sus indicaciones actuales, las posiciones de las diferentes asociaciones científicas al respecto y, lo más importante, brindar datos de la vida real en cuanto a su efectividad, seguridad y costos en los diferentes países donde se han estado usando.

Abstract The term Inflammatory Bowel Disease (IBD) is used to identify several entities, the two most important of which are Idiopathic Ulcerative Colitis (IUC) and Crohn's Disease (EC). Both are multifactorial in origin, are chronic and recurrent, are characterized by inflammation, have varying degrees of severity, and potentially involve other organs. In the last decade there has been renewed interest in these entities due to growing incidence and to the development of drugs called biologicals. For the first time, these drugs have changed the natural history of these diseases. They are produced or derived from living organisms and represent the fastest growing sector in the global pharmaceutical industry. Due to commercial interest, products similar but not identical to the original products have been developed and submitted to regulatory authorities. The European Medicines Agency has approved the first biosimilar for infliximab for all indications for which it has been approved. These include moderate to severe ulcerative colitis (UC) at all ages, moderate to severe Crohn's disease (CD) at all ages, fistulizing Crohn's disease, Psoriasic arthritis, Psoriasis, Ankylosing Spondylitis, and Rheumatoid Arthritis. 1 In this review, we define what these products are, as well as some concepts coined for their usage including extrapolation, substitution and interchangeability. We also make a historical review of their development, current indications, the positions of various scientific associations with respect to them, and - most importantly - provide real-life data regarding their effectiveness, safety and costs in countries where they have been used.

<b>Pharmacovigilance and Regulatory Science</b> / 薬剤疫学

The concept of regulatory science (RS) was proposed in 1987 by Dr. Mitsuru Uchiyama. He describes “RS is the science of optimizing scientific and technological developments according to objectives geared toward human health. It is also the science of predictive evaluation. In properly carrying out the mission of regulation, we must engage in appropriate research activities and harmonize technology with society's needs. This can be accomplished only by accurately comprehending and carefully exploiting the characteristics and trends of new technologies, reactions, materials, and substances”. This article describes the development and the present status of RS in Japan, US and EU. FDA (US authority) defines RS as the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products, and considers RS as a useful tool to accelerate the approval of new drugs and their delivery to patients. On the other hand, PMDA (Japanese authority) takes RS as the norms of regulatory activities in assessment and approval of useful drugs to meet the needs of patients. Pharmacovigilance (PV), defined by WHO, is the pharmacological science relating to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. PV focuses on safety of drugs and, therefore, can be a part of RS which deals with all aspects of pharmaceutical products including efficacy, safety and quality. The occurrence rate of adverse effects leading to death is revealed quite high by the studies in US and in Japan. Prediction and prevention of adverse effects are urgent matter that RS and PV should deal with.

Acute silver toxicity to Cnesterodon decemmaculatus (Pisces: Poeciliidae) in a river with extreme water-quality characteristics / Toxicidad aguda de la plata sobre Cnesterodon decemmaculatus (Pisces: Poeciliidae) en un río con características extremas de calidad de agua

Abstract. A 96 h acute silver toxicity test was performed in order to determine silver toxicity (LC50) to a local fish species (Cnesterodon decemmaculatus) in a river with extreme water-quality characteristics (Pilcomayo River, South America) and evaluate a cross-fish-species extrapolation of the Biotic Ligand Model. The dissolved silver concentrations tested were 0.095, 0.148, 0.175 and 0.285 mg Ag L−1. The 96 h Ag LC50 calculated for C. decemmaculatus was 0.14 mg L−1 (0.18 - 0.10) and the value predicted by BLM for Pimephales promelas was 0.051 mg Ag L−1. Test water elevated hardness may have exerted some protective effect. High mean water pH may have exerted a major protective effect by reducing silver free ion form and causing silver precipitation. The mortality pattern observed in this toxicity test may lend some support to a relationship between gill silver accumulation and mortality. A cross-fish-species extrapolation of Ag BLM for P. promelas was not valid in Pilcomayo River water and experimental conditions of this toxicity test.

Con el objeto de determinar la toxicidad de la plata en un pez nativo (Cnesterodon decemmaculatus), se llevó a cabo un ensayo estático de toxicidad aguda a 96 horas en un agua natural con características de calidad de agua, extremas (río Pilcomayo, Sudamérica). Asimismo, se evaluó una posible extrapolación inter-especie del Modelo del Ligando Biótico en el agua experimental. La concentración inicial de plata en solución en los distintos tratamientos fue de 0,095; 0,148; 0,175 y 0,285 mg Ag L −1 . La CL50 a las 96 horas calculada para C. decemmaculatus fue de 0,14 (0.18 - 0.10) mg Ag L−1 y el valor predicho por el BLM para Pimephales promelas fue de 0,051 mg Ag L−1. La elevada dureza del agua experimental pudo haber tenido algún efecto protector frente a la toxicidad de la plata. El valor medio de pH del ensayo fue elevado y posiblemente tuvo un gran efecto protector por reducción de la forma iónica libre y precipitación del metal. El patrón de mortalidad observado en este ensayo de toxicidad apoyaría la relación causa-efecto entre acumulación de plata en las branquias y mortalidad. La extrapolación inter-especie del BLM para P. promelas no resultó válida en el agua del río Pilcomayo y en las condiciones experimentales de este ensayo.

Model-based Meta-analysis of population pharmacokinetic models for paclitaxel in humans, rats and mice / 中国药学杂志

OBJECTIVE: To establish a quantitative method to evaluate the relationship on the PK parameters of paclitaxel among different species by using the model-based Meta-analysis, and provide a reference for species extrapolation and dose determination of new drug research and development. METHODS: Relevant literatures were searched in Pub-Med, CNKI, WanFang and other databases, and all search results were filtrated with the criteria and classified according to species. Using NONMEM to construct the model for human, rats and mice, respectively. Evaluating the performance of the model with normalized prediction distribution errors (NPDE), and calculating the correlation coefficient of species with allometric scaling method. RESULTS: The nonlinear mixed-effects model (NONMEM) was developed to describe the paclitaxel PK profiles for mice, rats and humans. A two-compartment pharmacokinetic model fitted the data well, and consistent with the reported results. The models were evaluated by NDPE, the final model was accurate and reliable. The allometric scaling of CL and Vtotal among three different species for paclitaxel was r2=0.9974 and r2=0.9372, respectively. CONCLUSION: Take paclitaxel for example, established the model-based meta-analysis, successfully, and evaluated the correlation on the PK parameters of paclitaxel among different species quantitatively.

Derivation of Ecological Protective Concentration using the Probabilistic Ecological Risk Assessment applicable for Korean Water Environment: (I) Cadmium

Probabilistic ecological risk assessment (PERA) for deriving ecological protective concentration (EPC) was previously suggested in USA, Australia, New Zealand, Canada, and Netherland. This study suggested the EPC of cadmium (Cd) based on the PERA to be suitable to Korean aquatic ecosystem. First, we collected reliable ecotoxicity data from reliable data without restriction and reliable data with restrictions. Next, we sorted the ecotoxicity data based on the site-specific locations, exposure duration, and water hardness. To correct toxicity by the water hardness, EU's hardness corrected algorithm was used with slope factor 0.89 and a benchmark of water hardness 100. EPC was calculated according to statistical extrapolation method (SEM), statistical extrapolation methodAcute to chronic ratio (SEMACR), and assessment factor method (AFM). As a result, aquatic toxicity data of Cd were collected from 43 acute toxicity data (4 Actinopterygill, 29 Branchiopoda, 1 Polychaeta, 2 Bryozoa, 6 Chlorophyceae, 1 Chanophyceae) and 40 chronic toxicity data (2 Actinopterygill, 23 Branchiopoda, 9 Chlorophyceae, 6 Macrophytes). Because toxicity data of Cd belongs to 4 classes in taxonomical classification, acute and chronic EPC (11.07 microg/l and 0.034 microg/l, respectively) was calculated according to SEM technique. These values were included in the range of international EPCs. This study would be useful to establish the ecological standard for the protection of aquatic ecosystem in Korea.

Associação de cetamina S(+) e midazolam pelo método convencional de cálculo e pela extrapolação alométrica em bugios-ruivo (Alouatta guariba clamitans): resposta clínica e cardiorrespiratória / S(+) ketamine and midazolam association by the conventional method of calculation and allometric extrapolation in red howler monkeys (Alouatta guariba clamitans): clinical and cardiopulmonary response

O objetivo deste estudo foi avaliar o protocolo de contenção química com cetamina S(+) e midazolam em bugios-ruivos, comparando o cálculo de doses pelo método convencional e o método de extrapolação alométrica. Foram utilizados 12 macacos bugios (Alouatta guariba clamitans) hígidos, com peso médio de 4,84±0,97kg, de ambos os sexos. Após jejum alimentar de 12 horas e hídrico de seis horas, realizou-se contenção física manual e aferiram-se os seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), tempo de preenchimento capilar (TPC), temperatura retal (TR), pressão arterial sistólica não invasiva (PANI) e valores de hemogasometria arterial. Posteriormente, os animais foram alocados em dois grupos: GC (Grupo Convencional, n=06), os quais receberam cetamina S(+) (5mg kg-1) e midazolam (0,5mg kg-1), pela via intramuscular, com doses calculadas pelo método convencional; e GA (Grupo Alometria, n=06), os quais receberam o mesmo protocolo, pela mesma via, utilizando-se as doses calculadas pelo método de extrapolação alométrica. Os parâmetros descritos foram mensurados novamente nos seguintes momentos: M5, M10, M20 e M30 (cinco, 10, 20 e 30 minutos após a administração dos fármacos, respectivamente). Também foram avaliados: qualidade de miorrelaxamento, reflexo podal e caudal, pinçamento interdigital, tempo para indução de decúbito, tempo hábil de sedação, qualidade de sedação, e tempo e qualidade de recuperação. O GA apresentou menor tempo para indução ao decúbito, maior grau e tempo de sedação, bem como redução significativa da FC e PANI de M5 até M30, quando comparado ao GC. Conclui-se que o grupo no qual o cálculo de dose foi realizado por meio da alometria (GA) apresentou melhor grau de relaxamento muscular e sedação, sem produzir depressão cardiorrespiratória significativa.

The aim of this study was to evaluate a protocol of chemical restraint comparing the conventional method of calculation (weight dose) and allometric extrapolation. Twelve healthy red howler monkeys (Alouatta guariba clamitans), average weight 4.84±0.97kg, male and female, were used for this study. After a 12-hour period of food restriction and 6 hours of water restriction, the animals were physically restraint and the following parameters were measured: heart rate (HR), respiratory rate (RR), capillary refill time (CRT), rectal temperature (RT), non invasive systolic arterial pressure (NISAP) and arterial blood gases analysis. The animals were distributed into two groups: CG (Conventional Group, n=6), in which the animals received S(+) ketamine (5mg kg-1) and midazolam (0.5mg kg-1), by intramuscular (IM) injection; and AG (Allometry Group, n=6), in which the animals also received S(+) ketamine and midazolan IM, but the doses were calculated by allometric extrapolation. Parameters were evaluated at the following moments: M5, M10, M20 and M30 (5, 10, 20 and 30 minutes after IM injection, respectively). Muscle relaxation, pedal and caudal reflexes, interdigital pinch, recumbency time, sedation's quality and duration, and recovery time and its quality were also evaluated. The AG had a faster time for recumbency, higher period and quality of sedation, and a significantly reduction on HR and SAP from M5 to M30 when compared to CG. It was concluded that allometric extrapolation presented a better muscle relaxation and sedation without significant cardiorespiratory depression.

A Novel Method for Effectively Preserving PPG Pulse Waveform Information / 航天医学与医学工程

Objective To reduce information loss in the refining processing of photoplethysmographic (PPG) pulse waveform. Method A novel PPG pulse waveform refining processing technique, named truncation/extrapolation technique was proposed. The key point of the proposed technique was to preserve the shape pattern of the most significant parts of the waveform at the expense of the distortion of the insignificant part. Thus, as compared with the conventional time-normalization method, the proposed technique ensured the accumulation coherent of the signal energy could be. Result Waveform analysis and comparison of experimental data between two methods verified the effectiveness of the proposed method in maintaining the most significant time domain features of the pulse waveform over a relatively wide range of the heart rate change, especially the shape and width of the dominant peak and the position of the dicrotic notch of the first derivative of PPG(dPPG). Conclusion The proposed method reduces the information loss in PPG pulse waveform refining processing, thus helps further processing of the PPG signal using some advanced signal processing techniques, such as waveform modeling and pattern recognition.

Bridging studies in clinical trials for new drug application / 中国临床药理学与治疗学

AIM:To introduce the concept of bridging study and its strategies in clinical trials for new drug application.METHODS:The concept of bridging study proposed in the ICH E5 guideline was introduced,with a case using bridging strategies in the new drug applications(NDAs)approved by the regulatory authority in Japan.The concrete mode and the development of bridging studies in Asia were summarized.RESULTS:With the application of the ICH E5,some countries and regions have successfully used the bridging strategy in the new drug applications.The bridging strategy is becoming a common and practical basis for the decision making of marketing approvals of new drugs in the Asia-pacific country.CONCLUSION:The currently bridging studies in Asia will play an important role in the extrapolation of foreign clinical data in new drug application.Using bridging study is very helpful in judging ethnic differences of drugs,reducing duplication of clinical trails,as well as shortening clinical development periods.

The extrapolation method in dosage is equivalent in effectiveness between man and experimental animals

Introduction on the factors influence dosage that is equivalent in effectiveness between animals. They comprised drug metabolism, minimum concentration have with effect in serum, the effective time, cellular respiration, organic weight rate comparison with body weight, heat production, cytochrom C, volume of kidney and body surface.

Cross-specialty linkage and extrapolation of resource-based relative value scales

This article describes methods used to produce a RBRVS (resource-based relative value scales), a common scale from two specialties (internal medicine and general surgery) and explains the newly developed extrapolation process within each specialty. To produce a common scale, we selected six 'same' services as linking services common to both specialties. Then we used the bi-weighted least squares method to locate all the same services on a single, common scale. By using the same method, we tried to extrapolate all the services within each specialty, not by the method of Kelly et al, dividing all the services within the specialty into families (small homogeneous groups of services) to apply charge-based ratios. To compare both methods, we extrapolated all the services of general surgery according to each method. With the correlation analysis to compare both results to American RVUs, we found that general surgery's RVUs from our own extrapolation method turned out to be more highly correlated with American RVUs than from Kelly's extrapolation method. Consequently, extrapolation with bi-weighted least squares method gave reasonable results.