Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice

The oral route is the most frequently used method of drug intake in humans. Oral administration of drugs to laboratory animals such as mice typically is achieved through gavage, in which a feeding needle is introduced into the esophagus and the drug is delivered directly into the stomach. This method requires technical skill, is stressful for animals, and introduces risk of injury, pain and morbidity. Here we investigated another method of drug administration. The benzimidazole derivative albendazole was emulsified in commercially available honey and administered to mice by voluntary feeding or gavage. Mice that received albendazole by either gavage or honey ingestion had virtually identical levels of serum albendazole sulfoxide, indicating that uptake and metabolism of albendazole was similar for both administration techniques. In addition, dosing mice with the albendazole-honey mixture for 8 wk had antiparasitic activity comparable to earlier studies using gavage for drug administration. Compared with gavage, voluntary ingestion of a drug in honey is more rapid, less stressful to the animal, and less technically demanding for the administrator. Because of its low cost and ready availability, honey presents a viable vehicle for drug delivery.

Fukushima Effects on Media Coverage and Attitudes in Germany

The paper examines the question, in how far Fukushima caused changes in the media coverage and the public opinion about nuclear power in Germany. To answer this question we used two methods, content analysis and survey. Firstly we analysed data from a quantitative content analyses to examine changes in the media coverage about nuclear power between 2010 and 2011. The first investigation period lasted from 10.07.2010 to 04.09.2010, immediately before the German Bundestag vote for the lifetime extension of nuclear power stations. The second investigation period covered the first two months of media coverage after Fukushima from 12.03.2011 to 16.5.2011. Secondly our data consist of a representative telephone panel survey (n=341). As the first wave was carried out from 16.8.2010 to 06.9.2010 and the second wave from 15.5.2011 to 04.06.2011 these data set gives us the unique possibility to investigate attitude changes about nuclear power on the individual level.

Fukushima und die Folgen. Medienberichterstattung, Öffentliche Meinung, Politische Konsequenzen

Am 11. März 2011 ereignete sich vor der japanischen Küste ein schweres Erdbeben. Es löste einen gewaltigen Tsunami aus, der an der Ostküste Japans schwere Schäden hervorrief und fast 20.000 Menschen das Leben kostete. Im Atomkraftwerk Fukushima verursachte der Tsunami eine Reaktorkatastrophe, in deren Folge insbesondere in Deutschland eine heftige Diskussion über die Atomenergie entflammte, die schließlich zum deutschen Atomausstieg führte. Die Reaktorkatastrophe erfuhr international eine große öffentliche (Medien-) Aufmerksamkeit und rief auch die kommunikationswissenschaftliche Forschung auf den Plan. Ergebnisse dieser Forschungen, die an verschiedenen Stellen unabhängig voneinander durchgeführt wurden, sind in diesem Band versammelt. In insgesamt 13 Beiträgen werden die medialen und öffentlichen Reaktionen auf das Unglück empirisch analysiert. Die Beiträge befassen sich zum einen mit der Darstellung der Atomenergie in historischer Vergleichsperspektive, wobei die Reaktorkatastrophe in Tschernobyl als Referenzpunkt für Fukushima diente. In weiteren Beiträgen wird die Dynamik der Berichterstattung in Deutschland fokussiert. Fünf Beiträge betrachten die Reaktionen der Medien in internationaler Vergleichsperspektive und weitere vier untersuchen die Reaktionen der Bevölkerung auf die Ereignisse in Fukushima. Die Beiträge beruhen überwiegend auf quantitativen Inhaltsanalysen und Befragungen, aber es wurden auch qualitative Methoden sowie automatisierten Verfahren der Textanalyse verwendet. Zudem wurden in mehreren Studien verschiedene Formen der Datenerhebung kombiniert. Durch die Zusammenführung der unterschiedlichen Perspektiven wird eine differenzierte Einschätzung der medialen und gesellschaftlichen Konsequenzen des Extremereignisses möglich. Die Umrisse eines Forschungsprogramms für die Nachhaltigkeits-, Energie- und Umweltkommunikation werden sichtbar.

Wirksamkeit des Programms "Reasoning and Rehabilitation Revised" für inhaftierte Frauen in der Schweiz - eine Erkundungsstudie

Hintergrund Bei dem revidierten Programm „Reasoning and Rehabilitation“ (R&R2) handelt es sich um einen gruppentherapeutischen Ansatz zur Behandlung spezifischer Probleme von Straftätern. Hier werden erstmals Effekte der deutschsprachigen Version für Mädchen und junge Frauen berichtet. Material und Methode Die Effekte des Gruppentrainings wurden bei 11 inhaftierten Frauen durch standardisierte Fragebogen erfasst. Hierbei interessierten Veränderungen sozial-interpersoneller, motivationaler, psychopathologischer und emotionsregulatorischer Merkmale. Zudem wurden die Zufriedenheit mit der Behandlung und der klinische Eindruck erhoben. Ergebnisse Die erfassten proximalen Effektmaße unterstützen überwiegend die Hypothese einer Wirksamkeit des R&R2 bei Frauen. Das Programm erwies sich als veränderungsinduzierend und wurde gut angenommen. Schlussfolgerung Die Ergebnisse dieser isolierten Evaluation des R&R2-Trainings bei Frauen weisen auf positive Veränderungen spezieller Problembereiche hin. Jedoch werden weiterführende Studien zum intra- und extramuralen Verhalten sowie distalen Rückfälligkeitsmaß benötigt.

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice

OBJECTIVES To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. METHODS AND MATERIALS Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. RESULTS The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. CONCLUSIONS Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice.

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.

A novel blood-sparing agent in cardiac surgery? First in-patient experience with the synthetic serine protease inhibitor MDCO-2010: a phase II, randomized, double-blind, placebo-controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

BACKGROUND Antifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients. METHODS In this phase II, double-blind, placebo-controlled study, 32 patients undergoing isolated primary coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were influence on coagulation, chest tube drainage, and transfusion requirements. RESULTS PK analysis showed linear dosage-proportional correlation between MDCO-2010 infusion rate and PK parameters. Blood loss was significantly reduced in the 3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011, respectively). The incidence of allogeneic blood product transfusions was lower with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited dosage-dependent antifibrinolytic effects through suppression of D-dimer generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM analysis as well as anticoagulant effects demonstrated by prolongation of activated clotting time and activated partial thromboplastin time. No systematic differences in markers of end organ function were observed among treatment groups. Three patients in the MDCO-2010 groups experienced serious adverse events. One patient experienced intraoperative thrombosis of venous grafts considered possibly related to the study drug. No reexploration for mediastinal bleeding was required, and there were no deaths. CONCLUSIONS This first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.