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Photodynamic treatment of oral squamous cell carcinoma cells with low curcumin concentrations
(2017)
Objective: Curcumin is known for its anti-oxidative, anti-inflammatory and anti-tumorigenic qualities at concentrations ranging from 3.7µg/ml to 55µg/ml. Therefore it is pre-destined for tumour therapy. Due to high oral doses that have to be administered and the low bioavailability of curcumin new therapy concepts have to be developed. One of these therapy concepts is the combination of low curcumin concentrations and UVA or visible light. Aim of our study was to investigate the influence of this treatment regime on oral squamous cell carcinoma cells.
Materials and Methods: A human oral squamous cell carcinoma cell line (HN) was pre-incubated with low curcumin concentrations (0.01µg/ml to 1µg/ml). Thereafter cell cultures were either left un-irradiated or were irradiated either with 1J/cm2 UVA or for 5min with visible light. Quantitative analysis of proliferation, membrane integrity, oxidative potential and DNA fragmentation were done.
Results: It could be shown that low curcumin concentrations neither influenced proliferation, nor cell morphology, nor cell integrity nor apoptosis. When combining these curcumin concentrations with UVA or visible light irradiation cell proliferation as well as development of reactive oxygen species was reduced whereas DNA fragmentation was increased. Concentration as well as light entity specific effects could be observed.
Conclusions: The present findings substantiate the potential of the combination of low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer of the oral mucosa.
Case description: A patient with a Barrett oesophageal carcinoma and a resection of the oesophagus with gastric pull-up developed swallowing disorders 6 years and 2 months after the operation. Within 1 year and 7 months two recurrences of the tumor at the anastomosis were found and treated with combined chemoradiotherapy or chemotherapy respectively. 7 years and 9 months after the operation local tumor masses and destruction were present with no ability to orally drink or eat (full feeding by jejunal PEG tube): quality of life was poor, as saliva and mucus were very viscous (pulling filaments) and could not be swallowed and had to be spat out throughout the day and night resulting in short periods of sleep (awaking from the necessity to spit out). In total the situation was interpreted more as a problem related to a feeling of choking (with food or fluid) in the sense of a functional dysphagia rather than as a swallowing disorder from a structural stenosis.
At that time acetylcysteine (2 times 200 mg per day, given via the PEG tube) and irradiation with water-filtered infrared-A (wIRA), a special form of heat radiation, of the ventral part of the neck and the thorax were added to the therapy. Within 1 day with acetylcysteine saliva and mucus became less viscous. Within 2 days with wIRA (one day with 4 to 5 hours with irradiation with wIRA at home) salivation decreased markedly and quality of life clearly improved: For the first time the patient slept without interruption and without the need for sleep-inducing medication. After 5 days with wIRA the patient could eat his first soft dumpling although drinking of fluids was still not possible. After 2½ weeks with wIRA the patient could eat his first minced schnitzel (escalope).
Following the commencement of wIRA (with typically approximately 90–150 minutes irradiation with wIRA per day) the patient had 8 months with good quality of life with only small amounts of liquid saliva and mucus and without the necessity to spit out. During this period the patient was able to sleep during the night.
Discussion: The main physiological effects of water-filtered infrared-A (wIRA) are: wIRA increases tissue temperature, tissue oxygen partial pressure and tissue perfusion markedly.
The five main clinical effects of wIRA are: wIRA decreases pain, inflammation and exudation/hypersecretion, and promotes infection defense and regeneration, all in a cross-indication manner. Therefore there is a wide range of indications for wIRA.
The effects of wIRA are based on both its thermal effects (relying on transfer of heat energy) and thermic effects (temperature-dependent effects, occurring together with temperature changes) as well as on non-thermal and temperature-independent effects like direct effects on cells, cell structures or cell substances.
Conclusion: Besides in a variety of other indications for wIRA, in cases of swallowing disorders (functional dysphagia) and hypersalivation or hypersecretion of mucus the use of wIRA should be considered as part of the treatment regime for improving a patient’s quality of life.
Wassergefiltertes Infrarot A (wIRA) ist eine spezielle Form der Wärmestrahlung mit hohem Eindringvermögen in das Gewebe und geringer thermischer Belastung der Hautoberfläche.
wIRA steigert deutlich Temperatur, Sauerstoffpartialdruck und Durchblutung im Gewebe und wirkt auch über nicht-thermische zelluläre Effekte.
wIRA mindert indikationsübergreifend Schmerzen (mit relevant weniger Analgetikabedarf), Entzündung und vermehrte Sekretion und fördert Infektionsabwehr und Regeneration.
Entsprechend breit sind die klinischen Anwendungsmöglichkeiten von wIRA.
wIRA ist ein kontaktfreies, verbrauchsmaterialfreies, leicht anzuwendendes, (selbst bei Wunden) als angenehm empfundenes Verfahren mit guter Tiefenwirkung und anhaltendem Wärmedepot.
wIRA ist u.a. einsetzbar zur Verbesserung der Heilung akuter und chronischer Wunden (wobei selbst eine ungestört "normal" ablaufende Wundheilung noch verbessert werden kann: schneller, schmerzärmer), bei Hauterkrankungen (wie vulgären Warzen, Herpes labialis, Herpes Zoster, Sklerodermie, Akne papulopustulosa; aktinischen Keratosen im Rahmen einer Photodynamischen Therapie), zur Resorptionsverbesserung topisch applizierter Substanzen, bei muskuloskeletalen Erkrankungen (wie Arthrosen, Arthritiden, Lumbago, ankylosierender Spondyloarthritis), zur Regeneration nach Sport, beim komplexen regionalen Schmerzsyndrom (CRPS), bei Polyneuropathien und in Kombination mit Strahlentherapie oder Chemotherapie in der Onkologie.
Volker Woltersdorff's essay 'Sexual Ghosts and the Whole of History: Queer Historiography, Post-Slavery Subjectivities, and Sadomasochism in Isaac Julien's "The Attendant"' discusses the controversial concept of wholeness in historiography with regard to the fascination with past horrors and the desire to do justice to their victims who retain a ghostly presence. The essay retraces how this commitment produces a dilemma, as it can result either in the aspiration to historical wholeness as full memoralization or alternatively in the radical rejection of wholeness as an impossible healing. Employing Elizabeth Freeman's notion of 'erotohistoriography', Woltersdorff introduces affect into the work of historiography in order to find an escape from the dilemmatic impasse between history's wholeness as pacified reconciliation and as ongoing catastrophe along the lines of Walter Benjamin. Sadomasochism is presented as a practice that may correspond most adequately to the paradoxical affect caused by traumatic history that continues to haunt the present. Indeed, re-enactments of historical oppression and violence occur frequently within the BDSM community. However, what distinguishes them from 'living history' re-enactments is their potential to modify affective attachments to history by altering the historical script. The essay elaborates this potential through Isaac Julien's 1993 short film "The Attendant", which, in a kind of queer re-enactment, overwrites the memory of colonial chattel slavery by a sadomasochistic encounter of a black guardian and a white visitor in a museum dedicated to the history of slavery. The film raises the ethical and political question of how to relate affectively to the legacy and ongoing presence of racism. Against this backdrop, the author argues that, through the BDSM scenario and its changes to the historical script, Julien's film represents and promotes a paradoxical way to perform both the memorialization and the forgetting of past horrors and pleasures. Here, historical wholeness acquires a conflicting double meaning of both achieving completeness and restoring integrity. Woltersdorff concludes by interpreting "The Attendant" as urging a utopian perspective, produced by the tension between the impossibility of history's wholeness and the necessary, reparative desire for it. The article concludes by highlighting the paradox that Julien's film shows wholeness 'to be impossible and yet necessary' and 'expresses a necessary desire made impossible'. While the essay explicitly engages with the figure of haunting, one could perhaps speak here also of plasticity insofar as the contradictory conjunction of remembering and forgetting seems to rely on a malleability of affects and on producing an affective economy that sustains the fantasmatic remembrance of a painful past through paradoxical pleasure but breaks with any pleasure derived from real inequality, injustice, or suffering imparted non-consensually.
Background: As members of the Notothenioidei - the dominant fish taxon in Antarctic waters - the family Bathydraconidae includes 12 genera and 17 species. The knowledge of these species inhabiting an isolated environment is rather fragmentary, including their parasite fauna. Studies on fish hosts and their associated parasites can help gain insights into even remote ecosystems and be used to infer ecological roles in food webs; however, ecological studies on the Bathydraconidae are scarce.
Results: In this study, stomach contents and parasite fauna of the Antarctic dragonfish species Parachaenichthys charcoti (n = 47 specimens) as well as of Gerlachea australis (n = 5), Gymnodraco acuticeps (n = 9) and Racovitzia glacialis (n = 6) were examined. The parasite fauna of P. charcoti consisted of eight genera represented by 11 species, with three of them being new host records. Overall, 24 parasite genera and 26 species were found in the sampled fish, including eleven new host records.
Conclusion: Analyses revealed that the majority of the parasite species found in the different fish hosts are endemic to Antarctic waters and are characterized by a broad host range. These findings are evidence for the current lack of knowledge and the need for further parasitological studies of fish species in this unique habitat.
Einleitung: Sirolimus, ein mechanistic target of rapamycin (mTOR)-Inhibitor, wurde trotz fehlender Zulassung zur Rejektionsprophylaxe nach Lebertransplantation als Reserveimmunsuppresivum in individuellen Indikationen eingesetzt. Als weiterer mTOR-Inhibitor wurde Everolimus 2012 für diese Indikation zugelassen. Ziel dieser Arbeit war eine systematische Analyse klinischer und pharmakologischer Daten im Rahmen einer Konversion einer Sirolimus- zu einer Everolimus-basierten Immunsuppression im Langzeitverlauf nach Lebertransplantation
Methoden und Patienten: Es erfolgte eine retrospektive, systematische Analyse biochemischer und klinischer Daten vor und nach der Umstellung bei 16 Patienten (Männer/Frauen, 8/8) nach Lebertransplantation, bei denen eine Umstellung der Immunsuppression von Sirolimus auf Everolimus erfolgt war mit besonderem Augenmerk auf Transplantatfunktion, Nierenfunktion und metabolische Komorbiditäten. Die statistische Analyse erfolgte mittels des Friedman-Tests zum Vergleich mehrerer abhängiger Stichproben, worauf bei signifikantem Ergebnis eine Post-hoc-Analyse folgte.
Ergebnisse: Die Patienten waren im Median (Minimum-Maximum) 10,1 (4-22,3) Jahre nach Lebertransplantation von Sirolimus auf Everolimus umgestellt worden. Bei der Mehrheit der Patienten war keine Dosisanpassung nach der Umstellung notwendig. Im Beobachtungszeitraum wurden keine Transplantatabstoßung oder klinisch relevante Komplikationen beobachtet. Zudem wurden vor und nach Umstellung keine signifikanten Unterschiede hinsichtlich Nierenfunktion, Diabetes mellitus oder arteriellem Blutdruck festgestellt. Die Bilirubin-Serumkonzentration war nach der Umstellung auf Everolimus niedriger, während AST-, ALT- und Triglycerid-Serumkonzentrationen signifikant höher waren.
Zusammenfassung: Diese Arbeit stellt die erste systematische Analyse der Konversion einer Sirolimus- auf eine Everolimus-basierten Immunsuppression im Langzeitverlauf nach Lebertransplantation dar. Relevante Komplikationen einschließlich Abstoßungen wurden nicht beobachtet.
Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients.Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire- HCV, Work Productivity and Activity-Specific Health Problem) before, during, and after treatment.A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to -24.4% by treatment week 12, up to -8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to -7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs.IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores.
Effective market discipline incentivizes financial institutions to limit their risk-taking behavior, making it a key element for financial regulation. However, without adequate incentives to monitor and control the risk-taking behavior of financial institutions market discipline erodes. As a consequence, bailing out financial institutions, as happened unprecedentedly during the recent financial crisis, may impose indirect costs to financial stability if bailout expectations of investors change. Analyzing US data covering the period between 2004 and 2014, Hett und Schmidt (2017) find that market participants adjusted their bailout expectations in response to government interventions, undermining market discipline mechanisms. Given these findings, policymakers need to take into account the potential effects on market discipline when deciding about public support to troubled financial institutions in the future. Considering the parallelism of events and public responses during the financial crisis as well as the recent developments of Italian banks, these results not only concern the US, but also have important implications for European financial markets and policy makers.
Der Proust'sche Fragebogen dient traditionell dazu sich kennenzulernen, sei es in einem französischen Salon, wo er einst entstand, sei es auf der letzten Seite eines deutschen Magazins. Wir haben unseren eigenen Fragebogen für den ZfL BLOG entworfen. Hier antwortet jetzt Karine Winkelvoss, französische Germanistin aus Rouen, die seit 2015 mit einem Forschungsstipendium der Alexander von Humboldt-Stiftung für erfahrene Wissenschaftler zu Gast am ZfL ist.
Der Literatur- und Medienwissenschaftler Tobias Wilke widmet sich in seinem Aufsatz der in der Forschung bislang unbeachtet gebliebenen Beziehung von "Aura" und "Medium". Dem Begriff des technischen Mediums, so Wilke, liegt ein nicht-technisches Konzept von Medialität zugrunde, das sich in enger Korrelation und Konvergenz mit dem Aura-Begriff herausbildet. Die Aura ist die sichtbare Umhüllung eines Objekts und damit ein Phänomen der optischen Wahrnehmung, in der die Konturen des Gegenstandes aufgelöst werden, wie Benjamin am Beispiel von Van Goghs "De sterrennacht" ausführt. Wilke verortet Benjamins Kunstwerk-Aufsatz an einer medienhistorischen Zäsur, die den Übergang von einem spiritistischen zu einem technologischen Verständnis von Medialität markiert.