Assessment of perfluoroalkyl substances in placenta by coupling salt assisted liquid-liquid extraction with dispersive liquid-liquid microextraction prior to liquid chromatography-tandem mass spectrometry.

The widespread use of perfluoroalkyl substances (PFAS) is resulting in a broad human exposure to these endocrine disrupting chemicals (EDCs), prompting biomonitoring research to evaluate its magnitude and impact, especially during critical windows of exposure such as fetal and perinatal periods. This study was focused on developing a method to determine 10 PFAS in placental tissue by combining salt-assisted liquid-liquid extraction with dispersive liquid-liquid microextraction and using liquid chromatography-tandem mass spectrometry. Chemometric strategies were applied to optimize the experimental parameters. The limit of quantification was 0.02 ng g-1 for all analytes, and the inter-day variability (as relative standard deviation) ranged from 7.9% to 13.8%. Recoveries ranged from 88.2% to 113.9%. The suitableness of the procedure was demonstrated by assessing the targeted compounds in 20 placenta samples. The highest concentrations were recorded for perfluorooctanoic acid and perfluorooctane sulfonate, with maximum concentrations of 0.62 and 1.02 ng g-1 and median concentrations of 0.13 and 0.53 ng g-1, respectively. Median concentrations of the other PFAS ranged from detected values to 0.08 ng g-1. This analytical procedure yields useful data on fetal exposure to PFAS.

Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI.

INTRODUCTION: The application of low-intensity electrical stimulation (LIES) to neural tissue increases neurochemical factors responsible for regeneration as nerve growth factor. Stem cell (SC) therapy for patients with Spinal cord injury (SCI) promote some increase functional improvement. OBJECTIVE: Investigate the electromyographic response in paraplegic dogs undergoing LIES and SC transplantation. METHODS: 27 dogs paraplegics with SCI were divided into three groups with different types of therapy. GADSC: two SC transplants (n = 9); GLIES: LIES (n = 8); GCOMB: two SC transplants and LIES (n = 10). Adipose derived mesenchymal stem cells (ADSCs) were transplanted by lumbar puncture in the amount of 1.2 × 106 cells/50 µL. Acupuncture needles positioned in the interspinous space were used for stimulation. The electrical stimulation was applied with a mean voltage ∼30 mV and four consecutive modulated frequencies (5 Hz, 10 Hz, 15 Hz and 20 Hz) within 5 min each. The patients motor performance was evaluated before (Pre) the procedure and after 30 (Post30) and 60 (Post60) days, from electromyography root mean square (EMGRMS) registered with subcutaneous electrodes in the vastus lateralis muscle, while the animals were in quadrupedal position. RESULTS: All three groups showed a significant intra-group increase of EMGRMS (Pre vs. Post30 or Pre vs. Post60). However, there were no statistically significant differences between Post30 and Post60. The inter-group test (GADSC X GLIES X GCOMB) did not present significance when compared the instants Pre (p = 0.34), Post30 (p = 0.78) and Post60 (p = 0.64). CONCLUSION: Some dogs recovered motor activity, expressed by the EMGRMS, in all groups, in pre vs. post (30 or 60 days) comparisons.

Papain wound dressings obtained from poly(vinyl alcohol)/calcium alginate blends as new pharmaceutical dosage form: Preparation and preliminary evaluation.

Transparent, soft, flexible, mechanically resistant films, which are ideal for use as wound dressings were prepared in the presence of 2% papain, a proteolytic enzyme that can play a role in the chemical debridement of the skin and can accelerate the healing process. The films, based on poly(vinyl alcohol):calcium alginate blends with increasing concentrations of polysaccharide (10, 20, and 30% v/v), were obtained by casting method. FTIR and DSC analyses were performed to assess the composition and miscibility of blends. Mechanical properties such as tensile strength, elasticity modulus, and elongation at breakpoint were evaluated. The influence of different concentrations of calcium alginate on physical attributes of films like wettability, swelling capacity and mechanical properties was determined. The stability of papain in the films was assessed indirectly by hemolytic activity assay employing direct contact method and confirmed by technique based on blood agar diffusion. Preliminary cytotoxicity was evaluated with the XTT method. The results showed that at the polymer concentrations tested, the blends were miscible. The increase in the content of the calcium alginate increased the wettability and swelling capacity of the films, which is desirable in wound dressings. On the other hand, mechanical resistance decreased without causing breakage of the films during the swelling tests. The hemolytic activity of the films was maintained during the studied period, suggesting the stability of papain in the proposed formulations. Cellular viability indicated that the films were non-toxic. The analysis of the results showed that it is possible to prepare interactive and bioactive wound dressing containing papain from blends of PVA and calcium alginate polymers.

Visualization, quantification and coordination of Ag+ ions released from silver nanoparticles in hepatocytes.

Silver nanoparticles (AgNPs) can enter eukaryotic cells and exert toxic effects, most probably as a consequence of the release of Ag+ ions. Due to the elusive nature of Ag+ ionic species, quantitative information concerning AgNP intracellular dissolution is missing. By using a synchrotron nanoprobe, silver is visualized and quantified in hepatocytes (HepG2) exposed to AgNPs; the synergistic use of electron microscopy allows for the discrimination between nanoparticular and ionic forms of silver within a single cell. AgNPs are located in endocytosis vesicles, while the visualized Ag+ ions diffuse in the cell. The averaged NP dissolution rates, measured by X-ray absorption spectroscopy, highlight the faster dissolution of citrate-coated AgNPs with respect to the less toxic PVP-coated AgNPs; these results are confirmed at the single-cell level. The released Ag+ ions recombine with thiol-bearing biomolecules: the Ag-S distances measured in cellulo, and the quantitative evaluation of gene expression, provide independent evidence of the involvement of glutathione and metallothioneins in Ag+ binding. The combined use of cutting-edge imaging techniques, atomic spectroscopy and molecular biology brings insight into the fate of AgNPs in hepatocytes, and more generally into the physicochemical transformations of metallic nanoparticles in biological environments and the resulting disruption of metal homeostasis.

Design, characterization and preliminary in vitro evaluation of a mucoadhesive polymer based on modified pectin and acrylic monomers with potential use as a pharmaceutical excipient.

Bio-based polymers have been reported to have applications in biomedical and pharmaceutical areas. Polysaccharides, especially prepared from plant sources, have served a variety of uses. This work aims to prepare a polymer for use as a pharmaceutical excipient containing a functionalized carbohydrate (pectin) and acrylic monomers (methyl methacrylate, butyl methacrylate and ethyl acrylate) via an emulsion polymerization technique. Carbon double bonds were incorporated into the pectin by reacting this natural polymer with glycidyl methacrylate. The methacrylated pectin was then polymerized with acrylic monomers by emulsion polymerization. The mucoadhesive performance of the materials was investigated by in vitro preliminary assays based on viscometric studies, texture analysis and film wettability. The obtained results showed that the synergistic viscosity increase with greater concentrations of modified pectin. The contact angle decreased, suggesting an increase in the wettability for polymers with large amounts of methacrylated pectin. The addition of mucin in lattices caused an increase in the intermolecular forces and in the work of adhesion. This corroborates the use of pectin as a mucoadhesive excipient for mucoadhesive drug delivery systems.

Specifications for hard condensed matter specimens for three-dimensional high-resolution tomographies.

Tomography is a standard and invaluable technique that covers a large range of length scales. It gives access to the inner morphology of specimens and to the three-dimensional (3D) distribution of physical quantities such as elemental composition, crystalline phases, oxidation state, or strain. These data are necessary to determine the effective properties of investigated heterogeneous media. However, each tomographic technique relies on severe sampling conditions and physical principles that require the sample to be adequately shaped. For that purpose, a wide range of sample preparation techniques is used, including mechanical machining, polishing, sawing, ion milling, or chemical techniques. Here, we focus on the basics of tomography that justify such advanced sample preparation, before reviewing and illustrating the main techniques. Performances and limits are highlighted, and we identify the best preparation technique for a particular tomographic scale and application. The targeted tomography techniques include hard X-ray micro- and nanotomography, electron nanotomography, and atom probe tomography. The article mainly focuses on hard condensed matter, including porous materials, alloys, and microelectronics applications, but also includes, to a lesser extent, biological considerations.

Design of prolonged release tablets using new solid acrylic excipients for direct compression.

The design of new excipients that extend the release of drugs from tablets over prolonged periods is essential in reaching enhanced therapeutic performances. In this sense, the objective of this study was to develop new excipients, based on acrylic monomers (ethyl acrylate, methyl methacrylate, and butyl methacrylate) for use in direct compression (DC). The polymeric excipients were prepared by suspension and emulsion polymerization reactions and were characterized by FTIR to confirm the polymerization reaction. For the success of direct compression, excipients must present good flow and compactability properties. Therefore, excipients were submitted to analysis of morphology (SEM), particle size and size distribution by laser diffraction, and powder density (bulk density and tapped density). The Carr index, Hausner ratio, flow ratio, and cotangent of the angle α were determined. Thereafter, the polymeric excipients were used to prepare inert matrices by DC using propranolol hydrochloride (PHCl) as a model drug. The tablets were evaluated for average weight, breaking force, and friability tests. The release profiles were determined, and the dissolution kinetics was studied. The results indicated that matrices prepared from excipients obtained by suspension polymerization (NWCB and PECB) presented a release of PHCl for a period exceeding 12h, most likely due to the higher micromeritic properties. The results suggested that the increase in the percentage of polymers, as well as in the compression time, resulted in a higher hardness of the matrix with a reduced rate release of the PHCl. Finally, in vitro preliminary tests showed that the polymeric excipients produced were non-toxic for the gingival fibroblasts.

Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery.

Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release.

[Spanish cross-sectional growth study 2008. Part I: weight and height values in newborns of 26-42 weeks of gestational age]. / Estudio transversal español de crecimiento 2008. Parte I: valores de peso y longitud en recién nacidos de 26-42 semanas de edad gestacional.

INTRODUCTION: Gestational age and neonatal anthropometric parameters are related to neonatal and postnatal morbidity and mortality. SUBJECTS AND METHODS: Weight and vertex-heel length were evaluated in 9.362 caucasian newborns (4.884 males and 4.478 females) products of single pregnancies, 26-42 weeks of gestational age, born between 1999 and 2002 in Vall d'Hebron (Barcelona, Spain) and Miguel Servet (Zaragoza, Spain) Children's Hospitals. RESULTS: Mean and standard deviation and percentile distribution values of weight, and length according to sex and gestational age are presented. A progressive increase in these parameters with gestational age and a sexual dimorphism was observed from the 30 week of gestational age onwards, with statistically-significant differences (p<0.01) from 35 weeks of gestational age. At 38 and 42 weeks of gestational ages these differences were 170 g, 160 g, 0.8 cm and 0.9 cm respectively. An increase in weight and length values in relation to previous Spanish studies (1987-1992) was also documented. CONCLUSIONS: A sexual dimorphism in intrauterine anthropometric growth parameters was observed. These parameters change with time and may be updated.

Estudio transversal español de crecimiento 2008. Parte I: valores de peso y longitud en recién nacidos de 26-42 semanas de edad gestacional / Spanish cross-sectional growth study 2008. Part I: weight and height values in newborns of 26-42 weeks of gestational age

Introducción: La edad gestacional, el peso y la longitud al nacer son factores relacionados con la morbilidad y mortalidad en el período neonatal y en la vida adulta. Sujetos y métodos: Valoración del peso y la longitud vértice-talón al nacer, en 9.362 recién nacidos vivos de raza caucásica (4.884 varones y 4.478 niñas) y de gestaciones únicas (26-42 semanas de edad gestacional), nacidos entre 1999 y 2002 en el Hospital Materno-Infantil Vall d’Hebron de Barcelona y en el Hospital Materno-Infantil Miguel Servet de Zaragoza. Resultados: Valores de la media y desviación estándar, y distribución percentilada del peso y de la longitud en los recién nacidos de ambos sexos según su edad gestacional. Existe un incremento progresivo con la edad gestacional y un dimorfismo sexual a partir de la semana 30 de gestación con diferencias estadísticamente significativas entre ambos sexos para ambos parámetros (p < 0,01) a partir de la semana 35 de edad gestacional. A las 38 y 42 semanas de edad gestacional los valores de la media para el peso y para la longitud son, respectivamente, 170 y 160 g, y 0,8 y 0,9 cm superiores en los varones que en las niñas. También se observó un incremento en los valores de la media de peso y longitud respecto a estudios previos (1987-1992). Conclusiones: Existe un dimorfismo sexual en el peso y la longitud de los recién nacidos pretérmino y a término. Estos parámetros cambian con el tiempo y deben ser revisados periódicamente (AU)

Introduction: Gestational age and neonatal anthropometric parameters are related to neonatal and postnatal morbidity and mortality. Subjects and methods: Weight and vertex-heel length were evaluated in 9.362 caucasian newborns (4.884 males and 4.478 females) products of single pregnancies, 26-42 weeks of gestational age, born between 1999 and 2002 in Vall d’Hebron (Barcelona, Spain) and Miguel Servet (Zaragoza, Spain) Children’s Hospitals. Results: Mean and standard deviation and percentile distribution values of weight, and length according to sex and gestational age are presented. A progressive increase in these parameters with gestational age and a sexual dimorphism was observed from the 30 week of gestational age onwards, with statistically-significant differences (p < 0.01) from 35 weeks of gestational age. At 38 and 42 weeks of gestational ages these differences were 170 g, 160 g, 0,8 cm and 0,9 cm respectively. An increase in weight and length values in relation to previous Spanish studies (1987-1992) was also documented. Conclusions: A sexual dimorphism in intrauterine anthropometric growth parameters was observed. These parameters change with time and may be updated (AU)

Triploidía completa 69XXY / Complete triploidy 69,XXY

No disponible

Crecimiento intrauterino retardado frente a pequeño para su edad gestacional / Retarded intrauterine growth versus small for gestational age

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Modelisation of an unspecialized quadruped walking mammal.

Kinematics and structural analyses were used as basic data to elaborate a dynamic quadruped model that may represent an unspecialized mammal. Hedgehogs were filmed on a treadmill with a cinefluorographic system providing trajectories of skeletal elements during locomotion. Body parameters such as limb segments mass and length, and segments centre of mass were checked from cadavers. These biological parameters were compiled in order to build a virtual quadruped robot. The robot locomotor behaviour was compared with the actual hedgehog to improve the model and to disclose the necessary changes. Apart from use in robotics, the resulting model may be useful to simulate the locomotion of extinct mammals.

Quantification by additive RT-PCR of HIV-1 RNA plasma levels in different stages of HIV-1 infection.

In this study, virion-associated RNA was measured in plasma from twenty six patients in various stages of HIV-1 disease by the additive RT-PCR method. Plasma viral RNA levels were inversely correlated (r = -0.72894) with total CD4+ cell counts and directly (r = 0.86964) with serum titre beta 2-microglobulin in chronically infected patients. This additive RT-PCR is based on a mathematical logistic adjustment of the standard curve and the use of an internal standard identical to the target molecule, which represents a control system for the efficiency of RT-PCR and allows a continuous assessment of the accuracy based on the recovery.

Angiotensin I-converting enzyme genotypes and angiotensin II receptors. Response to therapy.

In the present study, we studied angiotensin II type 1 (AT1) and type 2 (AT2) receptor messengers by quantitative reverse transcriptase-polymerase chain reaction. We examined peripheral blood mononuclear cells from 30 healthy subjects and 50 subjects with primary hypertension, in whom angiotensin I-converting enzyme genotype was determined, before and after 15 days of treatment with different antihypertensive drugs. The medication included a calcium channel antagonist, an angiotensin I-converting enzyme inhibitor, and a beta 1-blocker. We also studied the relationship between AT1 receptor gene expression and biochemical parameters of the renin-angiotensin system. AT1 receptor messenger levels were positively correlated with plasma renin activity in both normotensive and untreated hypertensive subjects. Increases of this messenger and plasma angiotensin II levels were correlated with the D allele in the same individuals. AT1 receptor messenger levels decreased significantly with angiotensin I-converting enzyme inhibitor treatment in subjects with the DD genotype, and a significant decrease was observed in subjects with the II and ID genotypes treated with a calcium antagonist. No changes were observed in mRNA with the beta 1-blocker. We conclude that the AT2 receptor is not expressed in peripheral leukocytes and that AT1 receptor messenger levels vary in relation to angiotensin I-converting enzyme genotype and pharmacological treatment. These results suggest that angiotensin I-converting enzyme genotype may be an important factor when deciding on antihypertensive therapy in individuals with primary hypertension.