Background
In humans, topically applied nanocarriers penetrate effectively into the hair follicles where they can be exploited for the localized and targeted treatment of skin disorders.
Objective
...The objective of the present study was to examine the applicability of particle‐based systems for follicular drug delivery in companion animals and livestock, which have a large follicular reservoir.
Animals
Skin samples from 10 beagle dogs, 14 Wistar rats and four ears from freshly slaughtered cross‐bred pigs were used.
Methods
Fluoresceinamine labelled poly (L‐lactide‐co‐glycolide) nanocarriers (256 or 430 nm) were applied on the different skin samples. After penetration, skin biopsies were removed and cryohistological cross sections prepared and investigated with regard to the follicular penetration depths (in μm ± standard deviation) of the nanocarriers using confocal laser scanning microscopy.
Results
In canine, rat and porcine hair follicles, the smaller nanoparticles were detected at mean follicular penetration depths of 630.16 ± 135.75 μm, 253.55 ± 47.36 μm and 653.40 ± 94.71 μm, respectively. The larger particles were observed at average follicular depths of 604.79 ± 132.42 μm; 262.87 ± 55.25 μm and 786.81 ± 121.73 μm, respectively, in canine, rat and porcine hair follicles. Statistically significant differences (P < 0.05) in the mean follicular penetration depths of the differently sized nanocarriers could be determined for the canine and porcine skin samples.
Conclusion
The mean follicular penetration depths of the differently sized nanocarriers were mostly significantly different between the different species, which might be due to different species‐specific follicular dimensions. This issue needs to be addressed specifically in further studies.
Résumé
Contexte
Chez l'homme, les nanovecteurs topiques pénètrent efficacement dans les follicules pileux où ils peuvent être utilisés en traitement localisé et ciblé des troubles cutanés.
Objectif
L'objectif de cette étude était d'examiner l'applicabilité des systèmes de particules pour la libération de médicament dans le follicule pileux chez les animaux de compagnie et d’élevage, qui ont des réservoirs folliculaires larges.
Sujets
Des échantillons cutanés de 10 chiens beagles, 14 rats Wistars et de quatre oreilles de porcs croisés récemment abattus.
Méthodes
Les nanovecteurs de fluorescéinamine (L‐lactide‐co‐glycolide) (256 ou 430 nm) ont été appliqués sur différents échantillons cutanés. Après pénétration, les biopsies cutanées ont été retirées et des coupes cryohistologiques ont été réalisées et analysées pour la profondeur de pénétration folliculaire des nanovecteurs (en μm ± déviation standard) par microscopie confocal à balayage laser.
Résultats
Pour les follicules pileux de chien, de rat et de porc, les plus petites nanoparticules ont été détectées à une profondeur de pénétration folliculaire moyenne respective de 630.16 ± 135.75 μm, 253.55 ± 47.36 μm et 653.40 ± 94.71 μm. Les particules les plus larges ont été observées à des profondeurs folliculaires moyennes respectives de 604.79 ± 132.42 μm; 262.87 ± 55.25 μm et 786.81 ± 121.73 μm pour les chiens, rats et porcs. Des différences statistiques significatives (P < 0.05) de la profondeur de pénétration folliculaire moyenne des différentes tailles de nanovecteurs ont pu être déterminées pour les échantillons de peau canine et porcine.
Conclusion
Les profondeurs de pénétration folliculaire moyenne des différentes tailles de nanovecteurs étaient significativement différentes entre les différents espèces ce qui pourraient être dû aux dimensions folliculaires différentes spécifiques d'espèces. Cette question doit être traitée spécifiquement dans d'autres études.
Resumen
Introducción
en humanos, la aplicación tópica de nanopartículas penetra de forma efectiva en los folículos pilosos y pueden ser utilizados para el tratamiento localizado y dirigido de las enfermedades de la piel.
Objetivo
el objetivo del presente estudio fue examinar la aplicabilidad de sistemas basados en nanoparticulas para la liberación de fármacos a nivel folicular en animales de compañía y ganado, los cuales tienen un reservorio grande folicular.
Animales
se utilizaron muestras de piel de 10 perros de raza Beagle, 14 ratas Wistar, y cuatro orejas de cerdos cruzados recientemente sacrificados.
Métodos
nanoparticulas con poli (L‐lactida‐co‐glicolido) marcadas con fluoresceinamina (256 o 430 nm) fueron aplicadas en las diferentes muestras de piel. Tras la penetración las biopsias de piel fueron retiradas, se prepararon criosecciones histológicas y se investigaron con respecto a la profundidad de penetración folicular (en micrómetros ± desviación estándar) de las nanoparticulas utilizando microscopía confocal de láser.
Resultados
en los folículos pilosos de perros, ratas y cerdos las nanopartículas más pequeñas fueron detectadas a una media de penetración folicular de 630,16 ± 135,75 μm, 253,55 ± 47,36 μm y 653,40 ± 94,71 μm, respectivamente. Las partículas de mayor tamaño se observan a profundidades medias de 604,79 ± 132,42 μm; 262,87 ± 55,25 μm y 786,81 ± 121,73 μm, respectivamente en folículos pilosos de perros, ratas y cerdos. Se determinaron diferencias estadísticamente significativas (P < 0,05) en la profundidad de penetración media folicular de los diferentes tamaños de nanopartículas para las muestras caninas y de cerdo.
Conclusión e importancia clínica
las profundidades medias de penetración folicular de los diferentes tamaños de nanopartículas fueron significativamente diferentes entre las distintas especies, lo cual puede ser debido a las diferentes dimensiones de los folículos entre las especies. Este hallazgo necesita ser investigado específicamente con otros estudios.
Zusammenfassung
Hintergrund
Beim Menschen penetrieren topisch aufgetragene Nanocarrier effektiv in die Haarfollikel, wo sie für die lokalisierte und gezielte Behandlung von Hauterkrankungen genützt werden können.
Ziel
Das Ziel dieser Studie war eine Untersuchung der Applizierbarkeit von Partikel‐hältigen Systemen zur Wirkstofflieferung in die Follikel bei Haus‐ und Nutztieren, die ein großes Follikel‐reservoir aufweisen.
Tiere
Hautproben von 10 Beagles, 14 Wistar Ratten und vier Ohren von frisch geschlachteten Schweinemischlingen wurden verwendet.
Methoden
Mit Fluorescinamin markierte Poly (L‐lactid‐co‐glycolid) Nanocarrier (256 und 430 nm) wurden auf die verschiedenen Hautproben aufgetragen. Nach dem Einziehen in die Haut wurden Hautbiopsien genommen und cryohistologische Kreuz‐Sektionsschnitte präpariert und in Bezug auf die follikuläre Penetrationstiefe (in μm ± Standardabweichung) der Nanocarrier mittels Confocaler Laser Scanning Mikroskopie untersucht.
Ergebnisse
In den Haarfollikeln von Hund, Ratte bzw Schwein wurden kleinere Nanopartikel bei einer durchschnittlichen follikulären Penetrationstiefe von 630,16 ± 135,75 μm, 253,55 ± 47,36 μm bzw 653,40 ± 94,71 μm gefunden. Die größeren Partikel wurden bei einer durchschnittlichen follikulären Tiefe von 604,79 ± 132,42 μm, 262,87 ± 55,25 μm bzw 786,81 ± 121,73 μm bei Haarfollikeln von Hund, Ratte bzw Schwein gefunden. Statistisch signifikante Unterschiede (P<0,05) bei der durchschnittlichen follikulären Penetrationstiefe der verschieden großen Nanocarrier konnte für die Hautproben der Hunde und der Schweine festgestellt werden.
Schlussfolgerung
Die durchschnittliche Penetrationstiefe der verschieden großen Nanocarrier waren hauptsächlich zwischen den verschiedenen Spezies statistisch signifikant unterschiedlich, was auf unterschiedliche Spezies‐spezifische follikuläre Dimensionen zurückzuführen sein könnte. Diese Tatsache sollte in zukünftigen Studien speziell untersucht werden.
要約
背景
ヒトにおいて、局所投与されたナノキャリアは限局化および標的化された皮膚疾患の治療のため利用される毛包内に効果的に浸透する。
目的
この研究の目的は、大型の毛包を保有する伴侶動物および家畜における、毛包への薬物輸送のための粒子ベースシステムの適応性を検査することである。
供与動物
10頭のビーグル、14頭のウィスター系ラット、および解体直後の交雑種の豚の耳4つからの皮膚材料を使用した。
方法
フルオレセインアミンをラベルしたポリ(L‐lactide‐co‐glycolide)ナノキャリア(256 or 430 nm)を異なる皮膚材料に塗布した。浸透後、皮膚生検を行い、凍結組織学的切片を作成し、共焦点レーザー走査顕微鏡を用いてナノキャリアの毛包浸透深度(μm ± 標準偏差)に関して調査を行った。
結果
イヌ、ラット、ブタの毛包において、平均毛包浸透深度がそれぞれ630.16 ± 135.75 μm、253.55 ± 47.36 μmおよび653.40 ± 94.71 μmで小さい方のナノ分子が検出された。イヌ、ラット、ブタの毛包において、大きな方のナノ分子は平均毛包深度がそれぞれ604.79 ± 132.42 μm、262.87 ± 55.25 μm および786.81 ± 121.73 μmで認められた。サイズの異なるナノキャリアの平均毛包浸透深度における統計学的な有意差(P < 0.05)はイヌとブタの皮膚材料で判明した。
結論
サイズの異なるナノキャリアの平均毛包浸透深度は異なる動物種間で大部分に有意差が存在したが、それは異なる動物種特異的毛包サイズに起因しているかもしれない。この内容は今後の研究において、具体的に取り組む必要がある。
摘要
背景
在人类,局部应用纳米载体可有效渗入到毛囊并在其中产生作用,进而对皮肤病进行靶向治疗。
目的
当前研究的目的为检测将药物输入毛囊的粒子系统,在有大容量毛囊的伴侣动物和家畜身上的使用。
动物
皮肤样本取自10只比格犬、14只维斯塔鼠和四只新屠宰的杂交猪的耳朵。
方法
将氨基荧光素标记的聚合物(羟基乙酸)纳米载体(256或430纳米)应用于不同的皮肤样本。渗透作用后,皮肤活检、制备组织细胞学交叉切片,并使用共聚焦激光扫描显微镜进行纳米载体毛囊渗透深度调查(单位是μm ±标准偏差)。
结果
在犬、鼠和猪的毛囊中,平均毛囊渗透深度分别为630.16 ± 135.75 μm、253.55 ± 47.36 μm和653.40 ± 94.71 μm时,可发现较小的纳米粒子。较大的粒子可见于平均深度分别为604.79 ± 132.42 μm、262.87 ± 55.25 μm 和786.81 ± 121.73 μm的毛囊。不同大小纳米载体的平均毛囊渗透深度在统计学上有显著差异(P < 0.05),这些差异可鉴别犬和猪的皮肤样本。
总结
不同种属间、不同大小纳米载体的平均毛囊渗透深度有明显不同,可能是因为不同种属的毛囊大小各异。这个问题在未来需要进一步研究。
Background – In humans, topically applied nanocarriers penetrate effectively into the hair follicles where they can be exploited for the localized and targeted treatment of skin disorders. Objective ‐ The objective of the present study was to examine the applicability of particle‐based systems for follicular drug delivery in companion animals and livestock, which have a large follicular reservoir. Conclusion – The mean follicular penetration depths of the differently sized nanocarriers were mostly significantly different between the different species, which might be due to different species‐specific follicular dimensions. This issue has to be specifically addressed in further studies.
The article analyses attitudes of European citizens towards gender equality. It describes how the EU script on gender relations emphasizes gender equality. Subsequently, the article analyses the ...extent to which citizens of different European countries agree with this idea, based on Eurobarometer dataThe analyses show a strong overall support for gender equality in the economic, political, and educational realms, but also differences between countries. In explaining these differences, we go beyond other studies not only by concentrating on endogenous characteristics of the analysed countries, but also by taking into account their levels of modernization, institutionalized gender regimes, and religious composition. Moreover; following neo-institutionalist theory, we include an exogenous variable -the influence of the EU - in multi-level analyses and can show that in addition to all endogenous variables, it also has an effect on attitudes towards gender relations.
Display omitted
► Investigate morphology of pentacene nanocolumn arrays fabricated by glancing angle deposition. ► Presence of interdigitated heterojunction OPVCs achieved by spin-coating PCBM. ► ...Comparison of three structure OPVCs performance.
Arrays of crystalline and regularly spaced pentacene nanocolumns, with a typical diameter of ca. 150
nm, were fabricated by glancing angle deposition on indium tin oxide substrates. The nanocolumn arrays were used to form large interface area organic heterojunction photovoltaic cells (OPVCs) by spin coating 6,6-phenyl-C61-butyric acid methyl ester (PCBM) as the acceptor material to fill the voids between nanocolumn. The light to electrical energy conversion efficiency of nanocolumn-based OPVCs was three times higher compared to planar heterojunction OPVCs of the same materials due to a significantly enlarged donor/acceptor interface area where exciton dissociation can occur. Further OPVC performance improvement was achieved through employing a thin pentacene electron-blocking layer before nanocolumn formation, which prevented electron current leakage to the anode.
Fiber Injection Molding is an innovative process for manufacturing 3D fiber formed parts. Within the process fibers are injected in a special mold through a movable nozzle by an air stream. This ...process allows a resource efficient production of near net-shape long fiber-preforms without cutting excess. For the properties of the preforms the mold filling is decisive, but current state of the art lacks methods to monitor mold filling online. In this paper a system for monitoring the mold filling based on image processing methods is presented. Therefor a camera and back-lighting has been integrated into a fiber injection mold. The detected filling level and fiber distribution is passed to the PLC of the fiber injection molding machine, which allows the operator to monitor the current mold filling state by means of a visual display. The image processing approach consists of preprocessing, binarization and segmentation. For the preprocessing and binarization several methods including a k-means algorithm, the Otsu thresholding method and a convolutional artificial neural network have been implemented and evaluated. Additionally the illumination of the mold has been investigated and found to have a very large influence on the quality of the results of all investigated methods. The results of the binarization are evaluated on the basis of ground truth images, where an absolute difference between labeled and binarized images is formed and the number of misinterpreted pixels is counted. Among the investigated methods, the method based on the Otsu threshold has been found to be the most efficient with regard to the achievable performance as well as to the correct detection of the current filling. The investigated approach allows the acquisition of more data about the mold filling process to improve models.
Abstract
Background
While Germany has a long tradition in HIV research with many well-established regional cohorts, there was a lack of collaborative efforts toward harmonized data collection and ...biobanking, both key strategies for efficient translational research projects. Key challenges are heterogeneity of data systems and privacy concepts, of existing study and data collection protocols, and sample collection, storage, and sharing.
Methods
In 2013, we established the Translational Platform HIV (TP-HIV) with support of the German Centre for Infection Research (DZIF) as a collaboration between university hospitals and specialized HIV care centers throughout Germany. After assessing the individual needs of all partner sites, we have taken comprehensive action to create a common platform for collaboration in all research stages. We developed protocols, rules of operation, biobanking strategies, and privacy concepts for all collaborating partner sites. Patients infected with HIV (PLWH) who sign the informed consent for the TP-HIV are pro- and retrospectively included in the cohort.
Results
To date, the TP-HIV infrastructure is implemented at 27 member sites from 11 cities, potentially extending to more than 20,000 patients currently treated for HIV across Germany. Facing the special needs in the German research environment, the TP-HIV established a unique data- and biomaterial collection allowing expedited translational research and reduce project overheads, regulatory burden, and data security regulations for investigators. By active surveillance, rapid access to individual patient groups such as patients with acute HIV infection, TP-HIV is an ideal platform for early phase clinical trials with new drug candidates. Researchers with clinical, biological, epidemiological, and statistical expertise have been brought together within the TP-HIV, which enables an effective translational chain from bench to bedside and back. New collaborations have been established with currently 23 active study protocols.
Conclusion
The TP-HIV has demonstrated to be a powerful tool for generating and testing research hypotheses in PLWH. In the future, we will work to further expand our network and address the pressing needs in the German research environment.
Disclosures
All authors: No reported disclosures.
Non-invasive imaging techniques in microbial disease models have delivered valuable insights in the intimate pathogen-host interplay during infection. Here we describe evaluation and validation of a ...transgenic bioluminescence reporter strain of the human-pathogenic mold Aspergillus fumigatus, one of the main fungal pathogens affecting immunocompromised individuals. Expression and surface display of the Gaussia princeps luciferase allowed sensitive and rapid detection of luminescence emitted from this strain after substrate addition, with photon fluxes strongly correlating to the amounts of fungal conidia or germlings. The reporter strain allowed spatio-temporal monitoring of infection in a cutaneous model of aspergillosis, where neutropenic mice maintained the fungal burden while immunocompetent ones were able to clear it entirely. Most importantly, antifungal therapy could be followed in this type of disease model making use of the bioluminescent A. fumigatus strain. In conclusion, combining sensitivity of the Gaussia luciferase with a surface display expression system in the fungal host allows longitudinal infection studies on cutaneous forms of aspergillosis, providing perspective on drug screening approaches at high-throughput.
Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. ...Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-kappaB (NF-kappaB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-kappaB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-kappaB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 microgml.sup.-1 LPS ± hydrocortisone (10.sup.-5 M), and NF-kappaB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-kappaB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-kappaB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such ...candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-kappaB (NF-kappaB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-kappaB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-kappaB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 microgml.sup.-1 LPS ± hydrocortisone (10.sup.-5 M), and NF-kappaB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Hydrocortisone inhibited LPS induced nuclear translocation of NF-kappaB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Hydrocortisone fails to inhibit LPS induced nuclear NF-kappaB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The international competition leads manufacturers in high-wage countries to focus more on high-value products, which often come at the disadvantage of small batch sizes. To remain competitive, the ...plant engineering for should be time and cost effective. One approach to achieve this are modular production lines. In the presented contribution, a product orientated web- service for the configuration of a modular production plant investigated. The resulting model then is interpreted by a code generator to generate a PLC line control. The approach is validated with a plant of metal hybrid carbon fiber seat rests.
Science Communication Leßmöllmann, Annette; Dascal, Marcelo; Gloning, Thomas
2019, Letnik:
17
eBook
This handbooks series aims to integrate knowledge of communication structures and processes. It is global in orientation, dedicated to cultural and epistemological diversity as well as different ...scholarly approaches. The series features volumes on 'messages, codes and channels', 'mode of address: communication situations and context', 'methodology in communication science' and 'application areas'. The latter features volumes devoted to a large range of specialist areas of communication science. The series as a whole aims at meeting the needs of undergraduates, postgraduates, academics and researchers across the area of communication studies.
PDF
