Dual local drug delivery of vancomycin and farnesol for mitigation of MRSA infection in vivo - a pilot study.

Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous implants create major surgical challenges with severe adverse effects, such as osteomyelitis. These infections are frequently caused by Staphylococcus aureus, often with high resistance to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). Due to the formation of impenetrable biofilms on implant surfaces, systemic antibiotic treatment has become exceedingly difficult. New solutions are pursued by combining several drugs using a controlled delivery system from specifically engineered implant surfaces. A sol-gel coating on titanium implants was previously developed with 20 wt % vancomycin and 30 wt % farnesol, with suppression of MRSA in vitro. The present study investigated the efficacy of sol-gel film coatings for controlled dual local delivery over 4 weeks utilising a rat infection model. The findings confirmed the viability of this new concept in vivo based on the differences observed between coatings containing vancomycin alone (SGV) and the dual-drug-containing coating with vancomycin and farnesol (SGVF). While both the SGVF and SGV coatings facilitated excellent preservation of the osseous microarchitecture, SGVF coating displayed a slightly higher potency for suppressing MRSA infiltration than SGV, in combination with a lower reactive bone remodelling activity, most likely by disturbing biofilm formation. The next step for advancing the concept of dual-drug delivery from sol-gel coatings to the clinic and confirming the promising effect of the SGVF coatings on reactive bone remodelling and suppressing MRSA infiltration is a study in a larger animal species with longer time points.

Reseda luteola L. extract displays antiproliferative and pro-apoptotic activities that are related to its major flavonoids.

Reseda luteola L. has been used as a dye due to its high luteolin content since ancient times. However, no pharmacological studies have been performed with Reseda extracts so far. Here, we have assessed antiproliferative and apoptosis-inducing effects of the Reseda extract RF-40. It contains 40% flavonoids, primarily luteolin, but also luteolin-7-O-glucoside and apigenin. RF-40 and the isolated flavonoids dose-dependently inhibited cell proliferation and induced apoptotic oligonucleosomes in PHA-stimulated peripheral blood mononuclar cells. These effects were not due to cytotoxicity as shown with a luminometric ATP assay. Dose-response curves of RF-40 and the isolated flavonoids were similar, with luteolin being the most effective isolated flavonoid. Comparison of RF-40 to its major flavonoids revealed that the pharmacological effects of the extract can mostly be attributed to luteolin. We conclude that Reseda extract is an interesting raw material not only for dyeing purposes but also for further pharmacological investigation.

Micrometastasis in breast cancer and other solid tumors.

Hematogenous distant metastasis is the leading cause of cancer-related death in breast cancer and other solid tumors. By applying sensitive immunocytochemical and molecular assays, disseminated tumor cells (DTC) in bone marrow (BM) can be detected in 20-40% of cancer patients without any clinical or even histopathological signs of metastasis and the presence of these DTC at primary diagnosis predicts the subsequent occurrence of overt metastases in bone and other organs. cDNA-microarray analysis on primary breast carcinomas from patients with and without tumor cells in BM revealed a predominant downregulation of potential metastasis-suppressor genes in BM-positive tumors. Thus, dissemination of tumor cells appears to be an early process associated with a specific molecular signature of the primary tumor.