On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling.

INTRODUCTION: Indium-111 when formulated as indium-111 oxine remains the gold standard for long term cell tracking, whereas radiometals for improved PET applications still have to be established. We here describe the on-cartridge formation of gallium-68, zirconium-89 and copper-64 complexes in small volumes suitable for cell labelling, including labelling of red blood cells (RBC) and white blood cells (WBC) and their biological evaluation in vivo. METHODS: Small volumes (1-2 mL) of tracers (oxine, tropolone) were directly prepared on an anion exchange cartridge (Sep-Pak QMA). Cells were radiolabelled and the labelling efficiency and efflux were evaluated. The in vivo biodistribution of copper-64-labelled WBC using [64Cu][Cu(oxinate)2] and [64Cu][Cu(tropolonate)2] was monitored in an infection and inflammation animal model using BALB/c mice. RESULTS: On-cartridge concentration of gallium-68, zirconium-89 and copper-64 enabled formation of oxine and tropolone tracers in small volumes with good yields (≥50%) and quality (extraction ≥90%). Prepared tracers radiolabelled the RBC comparable to indium-111 tracers and in vivo biodistribution of copper-64 labelled WBC showed clear accumulation of cells at the site of infection and inflammation. CONCLUSIONS: This on-cartridge preparation method enables simple formation of various PET tracers for cell radiolabelling. Zirconium-89 and copper-64 tracers radiolabelled cells with sufficient stability. Due to their longer half-life this approach could be promising for routine applications where longer evaluation periods for cell tracking are needed. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This novel approach for on-cartridge concentration and preparation of oxine and tropolone precursors with different positron emitters, in small volume and suitable pH, offers a versatile tool towards cell labelling for preclinical and clinical PET applications.

Efficacy of a polyphenolic extract from silver fir (Abies alba) bark on psoriasis: a randomised, double-blind, placebo-controlled trial.

Silver fir (Abies alba) bark extract contains a mixture of bioactive polyphenols. We tested their effectiveness in the treatment of psoriasis in order to further investigate the potential topical anti-inflammatory activity of polyphenols by means of a randomized, double-blind, placebo-controlled add-on clinical trial, after having examined their ability to downregulate the expression of IL-1ß cytokine in monocyte/macrophage primary cell culture. 61 patients with mild psoriasis met the inclusion criteria and were willing to comply with protocol requirements, were enrolled in the study. The severity of the disease was measured by psoriasis area severity index (PASI). Treatment efficacy was evaluated by assessing erythema (E, 0 to 4-point scale), desquamation (D, 0 to 4-point scale) and induration (I, 0 to 4-point scale) of lesions before and after the treatment. All patients enrolled in the study had symmetrical psoriasis plaques on the skin. All patients received O/V ointment with 2% of silver fir bark extract and/or placebo, respectively. We compared medications by right/left intra-patient comparison, so that the control group was always contralateral of the tested one. Location of the tested or control site was randomised, using a computer-generated randomisation schedule. Silver fir extract was well-tolerated. A superiority of active treatment above placebo, based on the clinical investigational PASI score system was observed by 15 % in all volunteers and in 40% regarding the improvement of psoriasis on elbows. However, statistical analysis showed no significant differences between placebo and active treatment with the extract from silver fir bark (p < 0.05).

DC-SIGN antagonists, a potential new class of anti-infectives.

DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions of DCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to enter DCs by being bound to DC-SIGN, escaping the normal lytic pathway in DCs' endosomes and avoiding the immune system defence system. A very similar mechanism of survival has been observed for some other pathogens. This makes DC-SIGN a receptor of interest in the design of distinctive anti-infectives that would inhibit DC-SIGN-pathogen interaction by blocking the very first step in pathogen infection. In this review we outline the development of DC-SIGN antagonists, focusing mainly on a glycomimetic approach. Based on the fact that DCSIGN binds mannose- and fucose-based oligo- and polysaccharides, their structural mimics have been designed and proved to inhibit pathogen-DC-SIGN interaction. Furthermore, recent in vitro studies have demonstrated that DC-SIGN antagonists block effectively the transmission of pathogens like HIV-1 and Ebola to CD4+ T cells. Although DC-SIGN has not been validated in vivo as a druggable target yet, we await future DC-SIGN antagonists as a new and highly promising group of novel anti-infectives.

Platelet gel stimulates proliferation of human dermal fibroblasts in vitro.

BACKGROUND: Platelet gel is a source of many soluble proteins that can modulate tissue regeneration. Dermal fibroblasts play an important role in tissue remodeling and wound healing. OBJECTIVE: The study was performed to investigate the influence of platelet gel and its active ingredients on the proliferation of human dermal fibroblasts in vitro. METHODS: A fibroblast culture was established from a normal human skin biopsy. Platelet gel was prepared from platelet-rich plasma (PRP) following the addition of calcified thrombin solution. Cell proliferation was measured by MTT assay. RESULTS: We showed that platelet gel, PRP, and thrombin stimulate the proliferation of dermal fibroblasts, and that stimulation by PRP is dose dependent. CONCLUSION: Platelet gel can be used to treat chronic skin defects.