Discrepancy between infectivity and antigenicity stabilization of oral poliovirus vaccine by a capsid-binding compound.

Two hundred forty pyridazinamine derivatives were tested for the ability to stabilize the antigenicity and infectivity of oral poliovirus vaccine subjected to 45 degrees C for 2 h. Seven compounds stabilized the antigenicity of all three vaccine strains and neutralized the viral particles in a way that is reversible by dilution. Of these, R 77975 (pirodavir) was selected for vaccine potency tests. Sabin type 2 and type 3 strains were subjected to 4, 25, 42, and 45 degrees C for 1 week in the presence and absence of R 77975. Although R 77975 particularly stabilized the infectivity of the most thermolabile vaccine strain (Sabin type 3), the protection did not exceed that of 1 M MgCl2. When virus was inactivated in the absence of R 77975, the native or N antigenicity changed in H antigenicity. However, in the presence of the capsid-binding compound, N antigenicity was preserved in particles that had lost infectivity

In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity.

Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds. Although its predecessor, R 61837, a substituted phenyl-pyridazinamine, was effective in inhibiting 80% of 100 serotypes tested (EC80) at concentrations above 32 micrograms/ml, pirodavir inhibits the same percentage of viruses at 0.064 micrograms/ml. Whereas R 61837 was active almost exclusively against rhinovirus serotypes of antiviral group B, pirodavir is broad spectrum in that it is highly active against both group A and group B rhinovirus serotypes. Pirodavir is also effective in inhibiting 16 enteroviruses, with an EC80 of 1.3 micrograms/ml. Susceptible rhinovirus serotypes were rendered noninfectious by direct contact with the antiviral compound. Their infectivity was not restored by dilution of virus-drug complexes, but was regained by organic solvent extraction of the compound for most serotypes. Neutralized viruses became stabilized to acid and heat, strongly suggesting a direct interaction of the compounds with viral capsid proteins. Mutants resistant to R 61837 (up to 85 times the MIC) were shown to bear some cross-resistance (up to 23 times the MIC) to the new compound, indicating that pirodavir also binds into the hydrophobic pocket beneath the canyon floor of rhinoviruses. Pirodavir acts at an early stage of the viral replication cycle (up to 40 min after infection) and reduces the yield of selected rhinoviruses 1,000- to 100,000-fold in a single round of replication. The mode of action appears to be serotype specific, since pirodavir was able to inhibit the adsorption of human rhinovirus 9 but not that of human rhinovirus 1A. Pirodavir is a novel capsid-binding antipicornavirus agent with potent in vitro activity against both group A and group B rhinovirus serotypes

Endovascular treatment of proximal anterior cerebral artery aneurysms.

INTRODUCTION: Aneurysms of the proximal segment of the anterior cerebral artery (A1A) are rare and challenging to treat. No information is available regarding their management by endovascular approach. The aim of this study was to report our experience with endovascular treatment (EVT) of A1As. PATIENTS AND METHODS: A retrospective review of our prospectively maintained database identified all A1As treated in our institution. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: From April 2004 to August 2008, eight patients were identified and presented with an unruptured A1A. All aneurysms but one were <3 mm in diameter and two aneurysms had a perforator at the neck. Surgery was performed in two patients with an aneurysm <2 mm. Six patients were treated by selective embolization including five patients with balloon-assisted coiling (BAC) and/or via a retrograde approach from the contralateral side through the anterior communicating artery. These adjunctive techniques were used to safely catheterize the sac or to protect a branch at the neck. All patients showed an excellent clinical outcome. A complete aneurysm occlusion was obtained in all but one patient. Follow-up imaging in four patients showed stable results. CONCLUSION: EVT of A1As is feasible and associated with good clinical and anatomical results. Because of their location, small size, and close relationship with perforators, EVT frequently requires the use of BAC and/or a retrograde approach. Our results suggest that EVT is an alternative therapeutic option to surgical clipping if the aneurysm size is compatible with selective embolization.Clinical TrialJournal Articleinfo:eu-repo/semantics/publishe

Stenting is improving and stabilizing anatomical results of coiled intracranial aneurysms.

INTRODUCTION: Stent-assisted coiling (SAC) is an alternative to surgical clipping for the treatment of wide-necked intracranial aneurysms (IA). However, little information is available concerning the long-term results of this treatment. The aim of this study was to report the long-term clinical and anatomical findings in 32 patients with 34 wide-necked IA treated by SAC. METHODS: A retrospective review of our prospectively maintained database identified all patients followed up for wide-necked IA treated by SAC. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: Thirty-two patients with 34 IA were identified including 25 asymptomatic patients, four with cranial nerve palsies, two with a subarachnoid hemorrhage, and one with transient ischemic attacks. Mean aneurysm size was 10.2 mm (range 3.5 to 26 mm). Embolization was successful in all patients and no procedure-related neurological morbidity or mortality was observed. Immediate anatomical results included nine complete occlusions (26.5%), two neck remnants (6%), and 23 incomplete occlusions (67.5%). Mean imaging follow-up of 20 months showed 18 further thrombosis (53%) and 16 stable results (47%). Finally, 27 aneurysms were completely occluded (79%), three had a neck remnant (9%), and four were incompletely occluded (12%). Asymptomatic and nonsignificant in-stent stenosis occurred in seven patients (22%). CONCLUSIONS: SAC is safe and effective for the treatment of wide-necked IA. Despite unsatisfying immediate aneurysm occlusion, the adjunctive effect of the stent is stabilizing or significantly improving long-term anatomical results.Journal Articleinfo:eu-repo/semantics/publishe