Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Reduced tumor growth in vivo and increased c-Abl activity in PC3 prostate cancer cells overexpressing the Shb adapter protein

Background  

Induction of apoptosis is one strategy for treatment of prostate cancer. The Shb adapter protein has been found to regulate apoptosis in various cell types and consequently human prostate cancer 3 (PC3) cells were transfected to obtain cells overexpressing Shb in order to increase our understanding of the mechanisms regulating PC3 cell apoptosis.     

Winkelstabile Plattenfixation

There are fundamental biomechanical differences between fixed-angle plate systems, also referred to as internal fixators, and conventional plate-screw fixation systems. Fixed-angle systems have rapidly gained widespread acceptance in recent years for almost all indications and anatomical sites. This contribution presents tips and tricks on their implantation and on the management of complications. Much of the information has already been presented elsewhere, in print or orally. Some of it is based on the authors’ own experience in their hospitals. The tips and tricks presented here are intended to help surgeons find pragmatic solutions to intraoperative problems.     

Diagnostische videoassistierte Thorakoskopie

Modern radiologic diagnostics show a variety of pathological changes in the mediastinum, pleura, and lung but no evidence on their histogenesis. Transbronchial and transthoracal fine-needle aspiration biopsy usually cannot yield detailed diagnostic results because of its small size. Sufficient and representative material can be obtained by thoracoscopy. Video-assisted thoracoscopy allows safe and fast diagnosis of diffuse lung diseases, pleural diseases including malignant mesothelioma, indeterminate peripheral lung nodule, and mediastinal masses. This gentle diagnostic method can give invaluable information guiding further management of the thoracic injury. Video-assisted thoracoscopy is a safe and effective guiding tool if performed by experienced thoracic surgeons able to convert to thoracotomy. It is to be noted that interpretation of intraoperative findings plays a decisive role in interdisciplinary diagnostics of intrathoracal diseases.     

Mandibular displacement in Angle Class II, Division 2 malocclusion

The effect of the treatment of Angle Class II, Division 2 malocclusion was studied in 22 children by x-ray cephalometry and by recording the relation between the retruded and the intercuspal mandibular positions. The treatment was performed in three phases. In the first phase the upper incisors were proclined, and the deep bite was corrected with an upper removable plate. In the second phase the distal occlusion was corrected with an activator. The result was retained in the third phase with a second activator designed for retention. The relation between the retruded (RCP) and the intercuspal (ICP) mandibular positions was recorded with wax bites and dental casts mounted in a modified gnathothesiometer. The anteroposterior distance between RCP and ICP was large before the start of the treatment. The distance was unchanged after proclination of the upper incisors and correction of the deep bite but decreased after correction of the distal occlusion and increased again somewhat during the retention phase. The proclination of the upper incisors and the correction of the deep bite (phase one of the treatment) did not result in mandibular anterior positioning. This fact and the results of the recordings of the relation between RCP and ICP were interpreted as evidence that the mandible is not posteriorly displaced in Class II, Division 2 malocclusion.     

Die Skelettszintigraphie beim neu diagnostizierten Prostatakarzinom

ZusammenfassungHintergrund Die Indikationsstellung zur Skelettszintigraphie beim neu diagnostizierten, unbehandelten Prostatakarzinom ist kontrovers.Patienten und Methoden In der vorliegenden retrospektiven Studie untersuchten wir 406 Patienten, die unabhängig von PSA-Wert und Histologie eine Staging-Skelettszintigraphie erhielten. Aus dem Patientengut evaluierten wir verschiedene Leitlinien und Empfehlungen bezüglich ihrer Vorhersagekraft. Die Kosten wurden gemäß EBM und GOÄ kalkuliert. Bei der Klassifikation von Skelettmetastasen prüften wir die Einteilungen nach Soloway, Crawford und Rigaud.Ergebnisse Eine positive Skelettszintigraphie im Sinne einer Skelettmetastasierung fanden wir bei 41 (10%) der 406 Patienten. Die Leitlinie der EAU hat sich sowohl hinsichtlich ihrer klinischen Wertigkeit als auch der Kosteneffizienz als wertvollste Empfehlung herausgestellt. Als Klassifikationssystem erwies sich die Rigaud-Klassifikation den anderen Einteilungen überlegen.Schlussfolgerung Gemäß der EAU-Leitlinie 2005 scheint die Skelettszintigraphie bei asymptomatischen Patienten mit einem PSA>20 ng/ml (G1/G2) sowie unabhängig vom PSA-Wert bei einem G3-Karzinom und lokal fortgeschrittenem Tumor indiziert. Als bestes Klassifikationssystem für Skelettmetastasen im Skelettszintigramm erwies sich die Einteilung nach Rigaud.     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.