Drug delivery to the hair follicle : role of follicular tight junctions as a biological barrier and the potential for targeting clobetasol nanocarriers

The porcine ear skin model has become a well-accepted in vitro model for follicular uptake studies of nanoparticle-based drug delivery systems. The present study further confirms the suitability and transferability of this model to human tissue regarding chemical composition of various hair follicle (HF) components, as well as expression and localization of follicular tight junction (TJ) proteins claudin-1, -3, -4, occludin, and ZO-1, by means of confocal Raman microscopy, qPCR, and immunostaining, respectively. Moreover, combining confocal Raman microscopy and optical profilometry allowed for a 3-D analysis of cyanoacrylate biopsies, the main analytical method to quantify follicular uptake, showing the removal of intact HFs and thus only further corroborating suitability and reliability of this technique. Furthermore, functionality of follicular TJs was investigated and a continuous TJ barrier was detected throughout the HF via an extracellular tracer molecule, confirming a second line of defense for xenobiotics. Modification of this barrier using EDTA was feasible. Lastly, the interplay of follicular uptake and interfollicular, transdermal permeation of three different nanocarriers for Clobetasol was evaluated. Although differing in the molecular architecture, all three particles displayed similar drug-releases and a similar reduction in skin permeation as opposed to dissolved drug. Follicular uptake, however, was particle-dependent. Massage amplified this uptake.Das Schweineohr-Hautmodell ist ein anerkanntes in vitro-Modell für follikuläre Aufnahmestudien von Nanopartikel-basierten Wirkstoffträgersystemen. Die vorliegende Arbeit bestätigt die Übertragbarkeit dieses Modells auf den Menschen hinsichtlich chemischer Zusammensetzung der verschiedenen Haarfollikel (HF)-Komponenten, sowie der Expression und Lokalisierung der follikulären Tight Junction (TJ) Proteine Claudin-1, -3, -4, Occludin und ZO-1, welche mittels konfokaler Raman Mikroskopie, qPCR und Immunfärbung gezeigt werden konnten. Durch die Kombination von konfokaler Raman-Mikroskopie und optischer Profilometrie wurde zudem eine 3D-Analyse von Cyanoacrylatbiopsien durchgeführt. Diese Analyse zeigte eine Entfernung des gesamten, intakten HF, wodurch Nutzen und Zuverlässigkeit der Technik bewiesen wurden. Ebenfalls wurde die Funktionalität der follikulären TJs untersucht. Mit Hilfe eines extrazellulären Tracermoleküls wurde eine intakte, kontinuierliche TJ-Barriere über den gesamten HF festgestellt, welche durch EDTA geöffnet werden konnte. Schließlich wurde ein Zusammenspiel zwischen follikulärer Aufnahme und Hautpermeation durch Verwendung dreier verschiedener mit Clobetasol-beladener Nanopartikel gezeigt. Obwohl sich diese in ihrem molekularen Aufbau unterscheiden, erzeugten alle ähnliche Arzneimittel-Freisetzungsprofile, sowie eine vergleichbare Minderung der Hautpermeation. Die follikuläre Aufnahme war jedoch Partikelabhängig. Massage verstärkte diese Aufnahme stets

EVIDÊNCIAS CLÍNICAS NO USO DA HIPODERMÓCLISE EM PACIENTES ONCOLÓGICOS:: REVISÃO INTEGRATIVA DA LITERATURA

Objetivo: identificar as evidências oriundas da literatura científica acerca da utilização da hipodermóclise na prática clínica em pacientes portadores de câncer. Método: Trata-se de revisão integrativa da literatura, cuja questão norteadora da pesquisa é “Quais são as evidências clínicas acerca da utilização da hipodermóclise em pacientes portadores de câncer?”. Foram utilizadas as bases eletrônicas de dados LILACS e MEDLINE. Resultados: A amostra foi de 12 artigos, cuja maioria era de origem norte-americana (41,6%), Os artigos trouxeram a definição da hipordermóclise e alguns destacaram a descrição da técnica em pacientes idosos com câncer, outras doenças crônicas e desidratação. Os maiores destaques nas publicações foram a maior adesão terapêutica pelo paciente na utilização da via subcutânea, bem como a facilidade e a segurança de utilização da técnica por meio da equipe de enfermagem, no hospital ou domicilio, além de ser de baixo custo. Conclusão: É consenso que é uma via satisfatória em pacientes com câncer e que é pouco utilizada ainda devido a falta de treinamento de profissionais

Film - Körper : Beiträge zu einer somatischen Medientheorie

Prof. Dr. Jens Schröter ist Herausgeber der Reihe und die Herausgeber der einzelnen Hefte sind renommierte Wissenschaftler und -innen aus dem In- und Ausland.Es kann als positives Zeichen für eine immer weiter marginalisiert zu werden drohende Disziplin wie die Filmwissenschaft gelten, dass mit der neuen Ausgabe der medienwissenschaftlichen Schriftenreihe Navigationen nach der Veröffentlichung von High Definition Cinema (Frühjahr 2011) nun erneut – ein Jahr später – ein Sammelband mit filmwissenschaftlichem Fokus vorliegt. Unter dem Titel Film|Körper versammelt er Bausteine zu einer Körpertheorie des Films, die zwischen poststrukturalistischer und phänomenologischer Tradition vermitteln wollen. Es handelt sich bei Film|Körper zugleich um die zweite Publikation des Forschungsprojekts Körpertheorie der Medien, geleitet von Ivo Ritzer (Universität Mainz) und Marcus Stiglegger (Universität Siegen). Eine erste Tagung fand bereits im Oktober 2010 an der Johannes Gutenberg-Universität Mainz statt und resultierte in dem Sammelband Global Bodies. Mediale Repräsentationen des Körpers (2012).

Correction: Gross anatomy, histology and blood vessel topography of the alimentary canal of the Inland Bearded Dragon (Pogona vitticeps).

[This corrects the article DOI: 10.1371/journal.pone.0234736.]

Gross anatomy, histology and blood vessel topography of the alimentary canal of the Inland Bearded Dragon (Pogona vitticeps).

Imaging techniques have proved to be crucial for diagnosis in reptile species. The topography of the internal organs of bearded dragons has been described in recent studies as meeting the small animal practitioners´ demand for knowledge concerning their anatomy. However, the nomenclature in the respective literature is not uniform, which could lead to misunderstandings concerning the respective and/or affected parts of the alimentary canal. Therefore, the aim of this study was to provide clear information on anatomy and histology of the alimentary canal of bearded dragons including supplying blood vessels. For the dissection of the alimentary canal, 11 Inland Bearded Dragons (Pogona vitticeps) were used (five males, six females), which had been euthanised for clinical reasons other than those concerning the digestive tract or had died spontaneously. The supplying arteries were demonstrated by injecting red latex into the aorta, while the intestinal veins were filled with blue latex via the portal vein. Microscopic examination was carried out on specimens of seven additional bearded dragons using routine histologic procedures. Macroscopically, the sections of the alimentary canal from oral to aboral were distinguished into oesophagus, stomach, small intestine, colic ampulla, colic isthmus, rectum and cloaca. Differentiation of the duodenum, jejunum and ileum was only possible when considering the bile duct, the vasculature and the histology of the organ wall. Arteries supplying the oesophagus and the final straight part of the large intestine originated from the aorta in a segmental manner. Between these, three unpaired arteries arose from the aorta. Their branches supplied stomach and intestine excluding its last part. Based on the findings of the present study, a nomenclature for the different parts of the alimentary canal and the supplying blood vessels of bearded dragons is suggested which is well understandable for veterinary practitioners and is based on zoological knowledge of reptiles

Specific anatomy and radiographic illustration of the digestive tract and transit time of two orally administered contrast media in Inland bearded dragons (Pogona vitticeps).

The aim of this study was to describe the specific gross and radiographic anatomy of the digestive tract of inland bearded dragons (Pogona vitticeps). Eleven bearded dragon cadavers of both sexes (6 females, 5 males) were dissected to examine, measure, and document the specific gross anatomy of the alimentary canal. Measurements collected from the cadavers included snout-vent length, total length of the alimentary canal, and the lengths of the individual sections of the gastrointestinal tract, including the esophagus, stomach, small intestine, ampulla coli, isthmus coli, rectum, and the distance from the coprodeum to the vent opening. Twenty-two healthy adult bearded dragons (13 females, 9 males) maintained under standardized husbandry conditions underwent a physical examination, blood collection, and whole-body dorsoventral and lateral survey radiographs; these animals were used to provide the radiographic images of the complete digestive tract. For the subsequent contrast passage studies, two different contrast media, barium sulfate (BaSO4, Barilux suspension) and an iodinated ionic radiocontrast agent (Sodium meglumine amidotrizoate [SMAT], Gastrografin), were used. Water-diluted Barilux suspension (dose 9 ml/kg) was administered orally to 5 bearded dragons, while Gastrografin (dose 5ml/kg) was administered orally to 21 bearded dragons. Four animals were used for both contrast media studies, but received a break of four weeks in between. Dorsoventral and laterolateral radiographs were collected at 0 (baseline), 15, 30, and 45 minutes and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, and 36 hours after each contrast medium was administered. Both contrast media were found to illustrate the alimentary tracts in the adult bearded dragons. Transit time was substantially faster with SMAT, and SMAT illustrated the entire gastrointestinal tract within 36 hours; BaSO4 did not fully illustrate the gastrointestinal tract in 36 hours. These results might serve as a guideline for the interpretation of subsequent contrast studies in this lizard species

Evidências clínicas no uso da hipodermóclise em pacientes oncológicos: revisão integrativa da literatura

Objetivo: identificar as evidências oriundas da literatura científica acerca da utilização da hipodermóclise na prática clínica em pacientes portadores de câncer. Método: Trata-se de revisão integrativa da literatura, cuja questão norteadora da pesquisa é “Quais são as evidências clínicas acerca da utilização da hipodermóclise em pacientes portadores de câncer?”. Foram utilizadas as bases eletrônicas de dados LILACS e MEDLINE. Resultados: A amostra foi de 12 artigos, cuja maioria era de origem norte-americana (41,6%), Os artigos trouxeram a definição da hipordermóclise e alguns destacaram a descrição da técnica em pacientes idosos com câncer, outras doenças crônicas e desidratação. Os maiores destaques nas publicações foram a maior adesão terapêutica pelo paciente na utilização da via subcutânea, bem como a facilidade e a segurança de utilização da técnica por meio da equipe de enfermagem, no hospital ou domicilio, além de ser de baixo custo. Conclusão: É consenso que é uma via satisfatória em pacientes com câncer e que é pouco utilizada ainda devido a falta de treinamento de profissionais

Sulfonated red and far-red rhodamines to visualize SNAP- and Halo-tagged cell surface proteins

The (in)ability to permeate membranes is a key feature of chemical biology probes that defines their suitability for specific applications. Here we report sulfonated rhodamines that endow xanthene dyes with cellular impermeability for analysis of surface proteins. We fuse charged sulfonates to red and far-red dyes to obtain Sulfo549 and Sulfo646, respectively, and further link these to benzylguanine and choloralkane substrates for SNAP-tag and Halo-tag labelling. Sulfonated rhodamine-conjugated fluorophores maintain desirable photophysical properties, such as brightness and photostability. While transfected cells with a nuclear localized SNAP-tag remain unlabelled, extracellular exposed tags can be cleanly visualized. By multiplexing with a permeable rhodamine, we are able to differentiate extra- and intracellular SNAP- and Halo-tags, including those installed on the glucagon-like peptide-1 receptor, a prototypical class B G proteincoupled receptor. In more complex biological systems, Sulfo549 and Sulfo646 labelled transfected neurons derived from induced pluripotent stem cells (iPSCs), allowing STED nanoscopy of the axonal membrane. Together, this work provides a new avenue for rendering dyes impermeable for exclusive extracellular visualization via self-labelling protein tags. We anticipate that Sulfo549, Sulfo646 and their congeners will be useful for a number of cell biology applications where labelling of intracellular sites interferes with accurate surface protein analysis

Sulfonated red and far-red rhodamines to visualize SNAP- and Halo-tagged cell surface proteins

The (in)ability to permeate membranes is a key feature of chemical biology probes that defines their suitability for specific applications. Here we report sulfonated rhodamines that endow xanthene dyes with cellular impermeability for analysis of surface proteins. We fuse charged sulfonates to red and far-red dyes to obtain Sulfo549 and Sulfo646, respectively, and further link these to benzylguanine and choloralkane substrates for SNAP-tag and Halo-tag labelling. Sulfonated rhodamine-conjugated fluorophores maintain desirable photophysical properties, such as brightness and photostability. While transfected cells with a nuclear localized SNAP-tag remain unlabelled, extracellular exposed tags can be cleanly visualized. By multiplexing with a permeable rhodamine, we are able to differentiate extra- and intracellular SNAP- and Halo-tags, including those installed on the glucagon-like peptide-1 receptor, a prototypical class B G proteincoupled receptor. In more complex biological systems, Sulfo549 and Sulfo646 labelled transfected neurons derived from induced pluripotent stem cells (iPSCs), allowing STED nanoscopy of the axonal membrane. Together, this work provides a new avenue for rendering dyes impermeable for exclusive extracellular visualization via self-labelling protein tags. We anticipate that Sulfo549, Sulfo646 and their congeners will be useful for a number of cell biology applications where labelling of intracellular sites interferes with accurate surface protein analysis