Taurolidine in the prevention and therapy of lung metastases

Objective: During surgery for colon carcinoma, tumour cells may spread into the blood and may lead to the development of distant metastases. The most frequent sites of metastases are the liver and lungs. A new therapeutic approach is required to prevent tumour implantation of freely circulating tumour cells during and after surgery and to treat established metastases. The aim of this prospective study was to observe the influence of long-term intravenous taurolidine on the development of lung metastases after intravenous injection of colon adenocarcinoma cells. Methods: Tumour cells (DHD/K12/TRb colon adenocarcinoma cell line, 1×106 cells) were injected into the right vena jugularis interna of BDIX rats. The animals (n=13) were randomised into three groups: group 1: tumour cell implantation without taurolidine application (control group); group 2: tumour cell implantation and simultaneous start of the taurolidine injection through osmotic pump, removal of the osmotic pump on day 7; group 3: tumour cell implantation on day 0 and start of the taurolidine injection through osmotic pump on day 14. Results: In the taurolidine groups, the number and size of lung metastases were significantly lower compared to the control group (p=0.018; p=0.018 and p=0.036; p=0.018). Although the results of the intravenous long-term therapy with taurolidine in group 2 did not reach statistical significance in comparison with the results of group 3, a positive trend was revealed: The mean number of metastases in group 2 was 18.2 versus 28.2 in group 3. Conclusions: The application of taurolidine tends to prevent the development of lung metastases. Furthermore, taurolidine seems to reduce established lung metastases in this in vivo model. Taurolidine may offer additional therapeutic options in patients with colon adenocarcinom

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

Bilateral Hip Dislocation: An Indicator for Emergent Full-Body Computed Tomography Scan in Polytraumatized Patients? A Case Report and Review of the Literature.

We present a rare case of traumatic bilateral asymmetric hip dislocation with pelvic fractures and a traumatic diaphragmatic hernia. A 53-year-old machinist was transferred to our emergency department with the suspicion of a bilateral hip dislocation after he was trapped between an elevator and the roof. Immediate closed reduction of the hips was not performed because of the expected risk of increasing hemodynamic instability with muscular relaxation. An emergent full-body computed tomography (CT) scan was made to assess injuries with need for further operative treatment. Thus, closed reduction of both hips was finally performed in the OR directly before the laparotomy for the diaphragmatic repair and the osteosynthesis of the anterior pelvic ring. A 12-month follow-up showed good general health condition with asymptomatic situation of the hip joints and the abdomen. The diagnostic work-up of patients with severe trauma is still debated, a randomized controlled trial showed no reduction of the in-hospital mortality with immediate full-body CT scan compared to a conventional radiological work-up. Traumatic hip dislocations (THDs) are always due to high-energy trauma and additional injuries are frequent. To attempt a closed reduction of THD, under general anesthesia can be life-threatening with unrecognized associated injuries. Therefore, THD can serve as selection criteria for immediate full-body CT scan to facilitate diagnosis and treatment of associated injuries sustained by the patient

Taurolidine in the prevention and therapy of lung metastases

OBJECTIVE: During surgery for colon carcinoma, tumour cells may spread into the blood and may lead to the development of distant metastases. The most frequent sites of metastases are the liver and lungs. A new therapeutic approach is required to prevent tumour implantation of freely circulating tumour cells during and after surgery and to treat established metastases. The aim of this prospective study was to observe the influence of long-term intravenous taurolidine on the development of lung metastases after intravenous injection of colon adenocarcinoma cells. METHODS: Tumour cells (DHD/K12/TRb colon adenocarcinoma cell line, 1 x 10(6) cells) were injected into the right vena jugularis interna of BDIX rats. The animals (n=13) were randomised into three groups: group 1: tumour cell implantation without taurolidine application (control group); group 2: tumour cell implantation and simultaneous start of the taurolidine injection through osmotic pump, removal of the osmotic pump on day 7; group 3: tumour cell implantation on day 0 and start of the taurolidine injection through osmotic pump on day 14. RESULTS: In the taurolidine groups, the number and size of lung metastases were significantly lower compared to the control group (p=0.018; p=0.018 and p=0.036; p=0.018). Although the results of the intravenous long-term therapy with taurolidine in group 2 did not reach statistical significance in comparison with the results of group 3, a positive trend was revealed: The mean number of metastases in group 2 was 18.2 versus 28.2 in group 3. CONCLUSIONS: The application of taurolidine tends to prevent the development of lung metastases. Furthermore, taurolidine seems to reduce established lung metastases in this in vivo model. Taurolidine may offer additional therapeutic options in patients with colon adenocarcinoma

Bilateral Hip Dislocation: An Indicator for Emergent Full-Body Computed Tomography Scan in Polytraumatized Patients? A Case Report and Review of the Literature

We present a rare case of traumatic bilateral asymmetric hip dislocation with pelvic fractures and a traumatic diaphragmatic hernia. A 53-year-old machinist was transferred to our emergency department with the suspicion of a bilateral hip dislocation after he was trapped between an elevator and the roof. Immediate closed reduction of the hips was not performed because of the expected risk of increasing hemodynamic instability with muscular relaxation. An emergent full-body computed tomography (CT) scan was made to assess injuries with need for further operative treatment. Thus, closed reduction of both hips was finally performed in the OR directly before the laparotomy for the diaphragmatic repair and the osteosynthesis of the anterior pelvic ring. A 12-month follow-up showed good general health condition with asymptomatic situation of the hip joints and the abdomen. The diagnostic work-up of patients with severe trauma is still debated, a randomized controlled trial showed no reduction of the in-hospital mortality with immediate full-body CT scan compared to a conventional radiological work-up. Traumatic hip dislocations (THDs) are always due to high-energy trauma and additional injuries are frequent. To attempt a closed reduction of THD, under general anesthesia can be life-threatening with unrecognized associated injuries. Therefore, THD can serve as selection criteria for immediate full-body CT scan to facilitate diagnosis and treatment of associated injuries sustained by the patient

Drug Derived Fluorescent Probes for the Specific Visualization of Cannabinoid Type 2 Receptor - A Toolbox Approach

Cannabinoid type 2 receptor (CB2R) is a fundamental part of the endocannabinoid signaling system (eCB system), and is known to play an important role in tissue injury, inflammation, cancer and pain. In stark contrast to its significance, the underlying signaling mechanisms and tissue expression profiles are poorly understood. Due to its low expression in healthy tissue and lack of reliable chemical tools, CB2R visualization in live cells remains uncharted. Here we report the development of a drug derived toolbox of highly potent, CB2R-selective fluorescent probes based on reverse design. Extensive validation in several applications such as CB2R detection in flow cytometry and time-resolved imaging, and the development of a novel fluorescent-based TR-FRET assay to generate kinetic and equilibrium binding data demonstrate the high versatility of our toolbox. These probes are the first to preserve affinity and efficacy in both human and mouse CB2R, a crucial aspect for preclinical translatability, and to enable imaging of CB2R internalization in living cells using confocal microscopy

Highly Specific, Fluorescent Cannabinoid Type 2 Receptor Probes Enable Applications in Microscopy, Flow Cytometry and FRET-based Binding Assays

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite its significance, researchers lack reliable tools to address questions concerning the complex mechanism of CB2R signaling and its downstream consequences, especially in cell-type and tissue-dependent contexts. Herein, we report highly specific CB2R fluorescent probes and their use in a variety of applications: flow cytometry with overexpressing as well as endogenously expressing cells, real-time confocal microscopy of living cells, and a novel FRET-based, CB2R binding assay amenable to high throughput screening.<br /