Effectiveness of cidofovir intralesional treatment in recurrent respiratory papillomatosis

To present the results of recurrent respiratory papillomatosis (RRP) treatment with surgical excision and adjuvant anti-viral cidofovir intralesional use and to examine the correlation between the cidofovir effectiveness and the patient previous history of multiple larynx procedures, age, extension of lesion and dose. 32 patients with laryngeal papillomas were treated with cidofovir in our Department between I.2009 and I.2011. The number of previous RRP debulking procedures ranged from 1 to 100. The intensity of papillomatosis differed from one anatomic site and moderate growth to four or five localizations with heavy extension. The number of injections per patient varied from 1 to 7, and the total volume of 5 mg/ml solution varied from 2 to 33 ml. The injections were combined with laser debulking of the lesions. In disperse papillomata, the injections were administered in particular anatomical sites in 4–6 weeks intervals, in massive lesions injections were repeated in the same anatomical site in 2–4 weeks. Complete remission was observed in 18 out of 32 patients. 13 patients showed remission in a place of cidofovir injection. One patient did not react to the drug. In four patients, new changes in injection places appeared. In two patients, hepatic toxic side effects were observed. Intralesional cidofovir injection has been shown to be an effective and safe therapy for laryngeal papillomatosis and should be considered in those patients who experienced disease relapse

Inhibition of Monkeypox virus replication by RNA interference

The Orthopoxvirus genus of Poxviridae family is comprised of several human pathogens, including cowpox (CPXV), Vaccinia (VACV), monkeypox (MPV) and Variola (VARV) viruses. Species of this virus genus cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. In this study, we investigated the potential of RNA interference pathway (RNAi) as a therapeutic approach for orthopox virus infections using MPV as a model. Based on genome-wide expression studies and bioinformatic analysis, we selected 12 viral genes and targeted them by small interference RNA (siRNA). Forty-eight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were limiting to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R) or an important gene in viral entry (E8L), inhibited viral replication in cell culture by 65-95% with no apparent cytotoxicity. Further analysis with wild-type and recombinant MPV expressing green fluorescence protein demonstrated that one of these constructs, siA6-a, was the most potent and inhibited viral replication for up to 7 days at a concentration of 10 nM. These results emphasis the essential role of A6R gene in viral replication, and demonstrate the potential of RNAi as a therapeutic approach for developing oligonucleotide-based drug therapy for MPV and other orthopox viruses

In vivo hemostatic efficacy of polyurethane foam compared to collagen and gelatin

<p>Topical hemostatic agents are used in all surgical disciplines. Most of these hemostats are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission. A newly developed biodegradable, fully synthetic hemostatic agent based on polyurethane foam (PU) with 55 % polyethylene glycol (PEG) would prevent these potential risks.</p><p>The hemostatic efficacy of this new agent was compared to gelatin and collagen in humans who underwent extraction of an upper and lower molar (split-mouth model). After extraction of a molar in the maxilla and mandible, a PU foam and collagen or gelatin were inserted in the extraction socket for 2 min. Hereafter, the agents were removed and stored in ethylenediaminetetraacetic acid to stop coagulation. Then, the concentration of coagulation parameters thrombin-antithrombin III (TAT) complexes, fibrinogen, and thromboxane B-2 (TxB(2)) in blood extracts from the agents was measured. The concentrations were also determined in baseline blood samples which were collected from the extraction socket.</p><p>The concentrations of TAT and TxB(2) were significantly increased, and fibrinogen concentration was significantly reduced compared to baseline wound blood concentrations indicating enhanced hemostasis. No significant differences were seen in the concentrations of these coagulation parameters in the three different hemostatic agents.</p><p>These results show that PU combined with 55 % PEG is a promising alternative for the animal-derived hemostatic agents.</p><p>The synthetic hemostatic agent could replace the animal-derived products like collagen and gelatin and therewith prevent the potential risk of pathogen transmission.</p>